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Sample records for ii diabetic rats

  1. [Effect of melatonin on antioxidant state under type ii diabetes at rat].

    PubMed

    Agarkov, A A; Popova, T N; Matasova, L V

    2013-01-01

    The effect of melatonin on the intensity of free radical processes and activities of superoxide dismutase (SOD, EC 1.15.1.1.) and catalase (EC 1.11.1.6) has been investigated in liver and blood serum of rats with diabetes mellitus type II. The development of diabetes was accompanied by the increase in biochemiluminescence parameters and the enzyme activities studied. Melatonin administration changed the parameters studied towards control values.

  2. Renal angiotensin II AT2 receptors promote natriuresis in streptozotocin-induced diabetic rats.

    PubMed

    Hakam, Amer C; Siddiqui, Athar H; Hussain, Tahir

    2006-02-01

    Angiotensin II AT2 receptors have been implicated to play a role in the regulation of renal/cardiovascular functions under pathological conditions. The present study is designed to investigate the function of the AT2 receptors on renal sodium excretion and AT(2) receptor expression in the cortical membranes of streptozotocin (STZ)-induced diabetic rats. The STZ treatment led to a significant weight loss, hyperglycemia, and decrease in plasma insulin levels compared with control rats. STZ-induced diabetic rats had significantly elevated basal urine flow, urinary sodium excretion rate (U(Na)V), urinary fractional sodium excretion, and urinary cGMP compared with control rats. Infusion of PD-123319, an AT2 receptor antagonist, caused a significant decrease in U(Na)V (mumol/min) in STZ-induced diabetic rats (1 +/- 0.09 vs. 0.45 +/- 0.1) but not in control rats (0.35 +/- 0.05 vs. 0.4 +/- 0.07). The decrease in U(Na)V was associated with a significant decrease in urinary cGMP levels (pmol/min) in STZ-induced diabetic rats (21 +/- 2 vs. 10 +/- 0.8) but not in control rats (11.75 +/- 3 vs. 12.6 +/- 2). The infusion of PD-123319 did not alter glomerular filtration rate (STZ: 0.3 +/- 0.02 vs. 0.25 +/- 0.03; control: 1.4 +/- 0.05 vs. 1.5 +/- 0.09 ml/min) or mean arterial pressure (STZ: 82 +/- 3 vs. 79 +/- 3.5; control: 90 +/- 4 vs. 89 +/- 4 mmHg), suggesting a tubular effect of the drug. Western blot analysis using an AT2 receptor antibody revealed a significantly enhanced expression of the AT2 receptor protein ( approximately 45 kDa) in brush-border ( approximately 50-fold) and basolateral membranes ( approximately 80-fold) of STZ-induced diabetic compared with control rats. In conclusion, our data suggest that the tubular AT2 receptors in diabetic rats are profoundly enhanced and possibly via a cGMP pathway promote sodium excretion in this model of diabetes.

  3. Angiotensin II receptor blocker telmisartan attenuates aortic stiffening and remodelling in STZ-diabetic rats

    PubMed Central

    2014-01-01

    Background Prevention or attenuation of diabetic vascular complications includes anti-hypertensive treatment with renin-angiotensin system inhibitors on account of their protective effects beyond blood pressure reduction. The present study aimed to investigate the effects of telmisartan, an angiotensin II type 1 receptor blocker (ARB), on blood pressure, aortic stiffening, and aortic remodelling in experimental type 1 diabetes in rats. Methods Diabetes was induced by streptozotocin (STZ) (65 mg/kg) in male Wistar rats. One diabetic group was treated for 10 weeks with telmisartan (10 mg/kg/day p/o). Pressure-independent aortic pulse wave velocity (PWV) was measured under anaesthesia after intravenous infusion of phenylephrine and nitroglycerine. Aortic wall samples were collected for histomorphometrical analysis. Results Untreated diabetes imposed differential effects on aortic stiffening, as demonstrated by increased isobaric PWV over a range of high blood pressures, but not at lower blood pressures. This was associated with loss and disruption of elastin fibres and an increase in collagen fibres in the aortic media. Treatment with telmisartan decreased resting blood pressure, reduced aortic stiffness, and partially prevented the degradation of elastin network within the aortic wall. Conclusions Telmisartan improved the structural and functional indices of aortic stiffening induced by untreated STZ-diabetes, demonstrating the importance of ARBs in the therapeutic approach to diabetic vascular complications. PMID:24920962

  4. Telmisartan, an angiotensin II type 1 receptor blocker, prevents the development of diabetes in male Spontaneously Diabetic Torii rats.

    PubMed

    Hasegawa, Goji; Fukui, Michiaki; Hosoda, Hiroko; Asano, Mai; Harusato, Ichiko; Tanaka, Muhei; Shiraishi, Emi; Senmaru, Takashi; Sakabe, Kazumi; Yamasaki, Masahiro; Kitawaki, Jo; Fujinami, Aya; Ohta, Mitsuhiro; Obayashi, Hiroshi; Nakamura, Naoto

    2009-03-01

    To assess the beneficial effects of the angiotensin II type 1 receptor blocker telmisartan on a non-obese animal model of reduced function and mass of islet beta-cells prior to the development of diabetes, Spontaneously Diabetic Torii (SDT) rats were treated with telmisartan at 8 weeks of age. At 24 weeks of age, the treatment with telmisartan dose-dependently ameliorated hyperglycemia and hypoinsulinemia, and high-dose (5 mg/kg/day) treated SDT rats did not developed diabetes. Real-time RT-PCR analysis revealed that treatment with high-dose telmisartan reduced mRNA expression of local renin-angiotensin system (RAS) components, components of NAD(P)H oxidase, transforming growth factor-beta1 and vascular endothelial growth factor in the pancreas of male SDT rats. Immunohistochemical and Western blot analyses revealed that treatment with telmisartan also reduced expression of p47(phox). These results suggest that treatment with telmisartan reduces oxidative stress by local RAS activation and protects against islet beta-cell damage and dysfunction. These findings provide at least a partial explanation for the reduced incidence of new-onset diabetes that has been observed in several clinical trials involving angiotensin II type 1 receptor blockers and ACE inhibitors.

  5. Effects of Icariside II on Corpus Cavernosum and Major Pelvic Ganglion Neuropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Bai, Guang-Yi; Zhou, Feng; Hui, Yu; Xu, Yong-De; Lei, Hong-En; Pu, Jin-Xian; Xin, Zhong-Cheng

    2014-01-01

    Diabetic erectile dysfunction is associated with penile dorsal nerve bundle neuropathy in the corpus cavernosum and the mechanism is not well understood. We investigated the neuropathy changes in the corpus cavernosum of rats with streptozotocin-induced diabetes and the effects of Icariside II (ICA II) on improving neuropathy. Thirty-six 8-week-old Sprague-Dawley rats were randomly distributed into normal control group, diabetic group and ICA-II treated group. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 2 groups including a saline treated placebo group and an ICA II-treated group (5 mg/kg/day, by intragastric administration daily). Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real time intracorporal pressure assessment. The penis was harvested for the histological examination (immunofluorescence and immunohistochemical staining) and transmission electron microscopy detecting. Diabetic animals exhibited a decreased density of dorsal nerve bundle in penis. The neurofilament of the dorsal nerve bundle was fragmented in the diabetic rats. There was a decreased expression of nNOS and NGF in the diabetic group. The ICA II group had higher density of dorsal nerve bundle, higher expression of NGF and nNOS in the penis. The pathological change of major pelvic nerve ganglion (including the microstructure by transmission electron microscope and the neurite outgrowth length of major pelvic nerve ganglion tissue cultured in vitro) was greatly attenuated in the ICA II-treated group (p < 0.01). ICA II treatment attenuates the diabetes-related impairment of corpus cavernosum and major pelvic ganglion neuropathy in rats with Streptozotocin-Induced Diabetes. PMID:25517034

  6. Centrally mediated erectile dysfunction in rats with type 1 diabetes: role of angiotensin II and superoxide.

    PubMed

    Zheng, Hong; Liu, Xuefei; Patel, Kaushik P

    2013-09-01

    Erectile dysfunction is a serious complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for penile erection. This study aims to determine the contribution of angiotensin (ANG) II in the dysfunction of central N-methyl-D-aspartic acid (NMDA)- and nitric oxide (NO)-induced erectile responses in streptozotocin-induced type 1 diabetic (T1D) rats. Three weeks after streptozotocin injections, rats were randomly treated with the angiotensin-converting enzyme inhibitor-enalapril, or the ANG II type 1 receptor blocker, losartan, or the superoxide dismutase mimetic, tempol, or vehicle via chronic intracerebroventricular infusion by osmotic mini-pump for 2 weeks. Central NMDA receptor stimulation or the administration of the NO donor, sodium nitroprusside (SNP)-induced penile erectile responses and concurrent behavioral responses were monitored in conscious rats. Two weeks of enalapril, losartan, or tempol treatment significantly improved the erectile responses to central microinjection of both NMDA and SNP in the paraventricular nucleus (PVN) of conscious T1D rats (NMDA responses-T1D+enalapril: 1.7 ± 0.6, T1D+losartan: 2.0 ± 0.3, T1D+tempol: 2.0 ± 0.6 vs. T1D+vehicle: 0.6 ± 0.3 penile erections/rat in the first 20 minutes, P < 0.05; SNP responses-T1D+enalapril: 0.9 ± 0.3, T1D+losartan: 1.3 ± 0.3, T1D+tempol: 1.4 ± 0.4 vs. T1D+vehicle: 0.4 ± 0.2 penile erections/rat in the first 20 minutes, P < 0.05). Concurrent behavioral responses including yawning and stretching, induced by central NMDA and SNP microinjections, were also significantly increased in T1D rats after enalapril, losartan, or tempol treatments. Neuronal NO synthase expression within the PVN was also significantly increased, and superoxide production was reduced in T1D rats after these treatments. These data strongly support the contention that enhanced ANG II mechanism/s within the PVN of T1D rats contributes

  7. Centrally Mediated Erectile Dysfunction in Rats with Type 1 Diabetes: Role of Angiotensin II and Superoxide

    PubMed Central

    Zheng, Hong; Liu, Xuefei; Patel, Kaushik P.

    2015-01-01

    Introduction Erectile dysfunction is a serious complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for penile erection. Aim To determine the contribution of angiotensin (ANG) II in the dysfunction of central N-methyl-D-aspartic acid (NMDA)-nitric oxide (NO)-induced erectile responses in streptozotocin-induced type 1 diabetic (T1D) rats. Methods Three weeks after streptozotocin injections, rats were randomly treated with the angiotensin-converting enzyme inhibitor-enalapril, or the ANG II type 1 receptor blocker, losartan, or the superoxide dismutase mimetic, tempol or vehicle via chronic intracerebroventricular infusion by osmotic mini-pump for 2 weeks. Main Outcome Measure Central NMDA receptor stimulation or the administration of the NO donor, sodium nitroprusside (SNP)-induced penile erectile responses and concurrent behavioral responses were monitored in conscious rats. Results Two weeks of enalapril, losartan or tempol treatment significantly improved the erectile responses to central microinjection of both NMDA and SNP in the paraventricular nucleus (PVN) of conscious T1D rats (NMDA responses – T1D+enalapril: 1.7 ± 0.6, T1D+losartan: 2.0 ± 0.3, T1D+tempol: 2.0 ± 0.6 vs. T1D+vehicle: 0.6 ± 0.3 penile erections/rat in the first 20 min, P < 0.05; SNP responses – T1D+enalapril: 0.9 ± 0.3, T1D+losartan: 1.3 ± 0.3, T1D+tempol: 1.4 ± 0.4 vs. T1D+vehicle: 0.4 ± 0.2 penile erections/rat in the first 20 min, P < 0.05). Concurrent behavioral responses including yawning and stretching, induced by central NMDA and SNP microinjections were also significantly increased in T1D rats after enalapril, losartan or tempol treatments. Neuronal NO synthase expression within the PVN was also significantly increased and superoxide production was reduced in T1D rats after these treatments. Conclusions These data strongly support the contention that enhanced ANG II mechanism/s within the PVN of T1D rats contributes

  8. Adipose Tissue-Derived Stem Cells Ameliorate Diabetic Bladder Dysfunction in a Type II Diabetic Rat Model

    PubMed Central

    Zhang, Haiyang; Qiu, Xuefeng; Shindel, Alan W.; Ning, Hongxiu; Ferretti, Ludovic; Jin, Xunbo; Lin, Guiting; Lin, Ching-Shwun

    2012-01-01

    Diabetes mellitus is associated with a broad constellation of voiding complaints that are often multifactorial and resistant to currently available therapies. The leading causes of diabetic bladder dysfunction (DBD) include alterations in the bladder smooth muscle, neuronal degeneration, and urothelial dysfunction. Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stromal cells, have shown promise as a novel tissue regenerative technique that may have utility in DBD. The aim of this study is to determine the efficacy and mechanism by which ADSCs may ameliorate DBD in rats fed a high-fat diet and treated with low-dose streptozotocin to induce type II diabetes. Improved voiding function was noted in ADSCs-treated rats as compared with phosphate-buffered saline-treated rats. Though some ADSCs differentiated into smooth muscle cells, paracrine pathway seems to play a main role in this process, thus resulting in reduction of apoptosis and preservation of “suburothelial capillaries network.” PMID:22008016

  9. Cardiac and renal function are progressively impaired with aging in Zucker diabetic fatty type II diabetic rats.

    PubMed

    Baynes, John; Murray, David B

    2009-01-01

    This study investigated the temporal relationship between cardiomyopathy and renal pathology in the type II diabetic Zucker diabetic fatty (ZDF) rat. We hypothesized that changes in renal function will precede the development of cardiac dysfunction in the ZDF rat. Animals (10 weeks old) were divided into four experimental groups: Lean Control (fa/?) LC(n = 7), untreated ZDF rats (n = 7) sacrificed at 16 weeks of age, and LC (n = 7) untreated ZDF rats (n = 9) sacrificed at 36 weeks of age. LV structural/functional parameters were assessed via Millar conductance catheter. Renal function was evaluated via markers of proteinuria and evidence of hydronephrosis. LV mass was significantly less in the ZDF groups at both time points compared to age-matched LC. End diastolic volume was increased by 16% at 16 weeks and by 37% at 36 weeks of age (p < 0.05 vs. LC). End diastolic pressure and end systolic volume were significantly increased (42% and 27%respectively) at 36 weeks of age in the ZDF compared to LC. Kidney weights were significantly increased at both 16 and 36 week in ZDF animals (p < 0.05 vs. LC). Increased urinary albumin and decreased urinary creatinine were paralleled by a marked progression in the severity of hydronephrosis from 16 to 36 weeks of age in the ZDF group. In summary, there is evidence of progressive structural and functional changes in both the heart and kidney, starting as early as 16 weeks,without evidence that one pathology precedes or causes the other in the ZDF model of type II diabetes.

  10. Compromised Neurotrophic and Angiogenic Regenerative Capability during Tendon Healing in a Rat Model of Type-II Diabetes.

    PubMed

    Ahmed, Aisha S; Li, Jian; Abdul, Alim M D; Ahmed, Mahmood; Östenson, Claes-Göran; Salo, Paul T; Hewitt, Carolyn; Hart, David A; Ackermann, Paul W

    2017-01-01

    Metabolic diseases such as diabetes mellitus type-II (DM-II) may increase the risk of suffering painful connective tissue disorders and tendon ruptures. The pathomechanisms, however, by which diabetes adversely affects connective tissue matrix metabolism and regeneration, still need better definition. Our aim was to study the effect of DM-II on expressional changes of neuro- and angiotrophic mediators and receptors in intact and healing Achilles tendon. The right Achilles tendon was transected in 5 male DM-II Goto-Kakizaki (GK) and 4 age-matched Wistar control rats. The left Achilles tendons were left intact. At week 2 post-injury, NGF, BDNF, TSP, and receptors TrkA, TrkB and Nk1 gene expression was studied by quantitative RT-PCR (qRT-PCR) and their protein distribution by immunohistochemistry in intact and injured tendons. The expression of tendon-related markers, Scleraxis (SCX) and Tenomodulin (TNMD), was evaluated by qRT-PCR in intact and injured tendons. Injured tendons of diabetic GK rats exhibited significantly down-regulated Ngf and Tsp1 mRNA and corresponding protein levels, and down-regulated Trka gene expression compared to injured Wistar controls. Intact tendons of DM-II GK rats displayed reduced mRNA levels for Ngf, Tsp1 and Trkb compared to corresponding intact non-diabetic tendons. Up-regulated Scx and Tnmd gene expression was observed in injured tendons of normal and diabetic GK rats compared to intact Wistar controls. However, these molecules were not up-regulated in injured DM-II GK rats compared to their corresponding controls. Our results suggest that DM-II has detrimental effects on neuro- and angiotrophic pathways, and such effects may reflect the compromised repair seen in diabetic Achilles tendon. Thus, novel approaches for regeneration of injured, including tendinopathic, and surgically repaired diabetic tendons may include therapeutic molecular modulation of neurotrophic pathways such as NGF and its receptors.

  11. Compromised Neurotrophic and Angiogenic Regenerative Capability during Tendon Healing in a Rat Model of Type-II Diabetes

    PubMed Central

    Ahmed, Aisha S.; Li, Jian; Abdul, Alim M. D.; Ahmed, Mahmood; Östenson, Claes-Göran; Salo, Paul T.; Hewitt, Carolyn; Hart, David A.; Ackermann, Paul W.

    2017-01-01

    Metabolic diseases such as diabetes mellitus type-II (DM-II) may increase the risk of suffering painful connective tissue disorders and tendon ruptures. The pathomechanisms, however, by which diabetes adversely affects connective tissue matrix metabolism and regeneration, still need better definition. Our aim was to study the effect of DM-II on expressional changes of neuro- and angiotrophic mediators and receptors in intact and healing Achilles tendon. The right Achilles tendon was transected in 5 male DM-II Goto-Kakizaki (GK) and 4 age-matched Wistar control rats. The left Achilles tendons were left intact. At week 2 post-injury, NGF, BDNF, TSP, and receptors TrkA, TrkB and Nk1 gene expression was studied by quantitative RT-PCR (qRT-PCR) and their protein distribution by immunohistochemistry in intact and injured tendons. The expression of tendon-related markers, Scleraxis (SCX) and Tenomodulin (TNMD), was evaluated by qRT-PCR in intact and injured tendons. Injured tendons of diabetic GK rats exhibited significantly down-regulated Ngf and Tsp1 mRNA and corresponding protein levels, and down-regulated Trka gene expression compared to injured Wistar controls. Intact tendons of DM-II GK rats displayed reduced mRNA levels for Ngf, Tsp1 and Trkb compared to corresponding intact non-diabetic tendons. Up-regulated Scx and Tnmd gene expression was observed in injured tendons of normal and diabetic GK rats compared to intact Wistar controls. However, these molecules were not up-regulated in injured DM-II GK rats compared to their corresponding controls. Our results suggest that DM-II has detrimental effects on neuro- and angiotrophic pathways, and such effects may reflect the compromised repair seen in diabetic Achilles tendon. Thus, novel approaches for regeneration of injured, including tendinopathic, and surgically repaired diabetic tendons may include therapeutic molecular modulation of neurotrophic pathways such as NGF and its receptors. PMID:28122008

  12. In vivo creatine kinase reaction kinetics at rest and stress in type II diabetic rat heart

    PubMed Central

    Bashir, Adil; Coggan, Andrew R.; Gropler, Robert J.

    2015-01-01

    Abstract The effects of type II diabetes on cardiac creatine kinase (CK) enzyme activity and/or flux are unknown. We therefore measured steady‐state phosphocreatine (PCr) and adenosine triphosphate (ATP) content and forward CK reaction kinetic parameters in Zucker Diabetic Fatty (ZDF) rat hearts, a type II diabetes research model. At baseline the PCr to ATP ratio (PCr/ATP) was significantly lower in diabetic heart when compared with matched controls (1.71 ± 0.21 vs. 2.26 ± 0.24, P < 0.01). Furthermore, the forward CK reaction rate constant (kf) was higher in diabetic animals (0.52 ± 0.09 s−1 vs. 0.35 ± 0.06 s−1, P < 0.01) and CK flux calculated as a product of PCr concentration ([PCr]) and kf was similar between two groups (4.32 ± 1.05 μmol/g/s vs. 4.94 ± 1.23 μmol/g/s, P = 0.20). Dobutamine administration resulted in similar increases in heart rate (~38%) and kf (~0.12 s−1) in both groups. No significant change in PCr and ATP content was observed with dobutamine. In summary, our data showed reduced PCr/ATP in diabetic myocardium as an indicator of cardiac energy deficit. The forward CK reaction rate constant is elevated at baseline which might reflect a compensatory mechanics to support energy flux through the CK shuttle and maintain constant ATP supply. When hearts were stimulated similar increase in kf was observed in both groups thus it seems that CK shuttle does not limit ATP supply for the range of workload studied. PMID:25626865

  13. Cross-talk related to insulin and angiotensin II binding on myocardial remodelling in diabetic rat hearts.

    PubMed

    Maharsy, Wael M; Kadi, Lina N; Issa, Nahla G; Bitar, Khalil M; Der-Boghossian, Asdghig H; Abrahamian, Roy; Bikhazi, Anwar B

    2007-06-01

    This study focused on the regulation and affinity modulation of angiotensin II (Ang II) binding to its receptor subtypes (AT(1)- and AT(2)-receptor) in the coronary endothelium (CE) and cardiomyocytes (CM) of Sprague-Dawley male rats in normal (N), normal treated with losartan (NL), streptozotocin-induced diabetic (D), insulin-treated diabetic (DI), losartan-treated diabetic (DL), and diabetic co-treated with insulin and losartan (DIL). Heart perfusion was used to estimate Ang II binding affinity (tau=1/k-(n)) to its receptor subtypes on CE and CM. Diabetes decreased tau value on CE and increased it on CM as compared to normal. In DL group, the tau value decreased on CE but was normalised on CM. Insulin treatment alone (DI) or with losartan (DIL) restored t to normal on both CE and CM. Western blot results for AT(1)-receptor density showed an increase in diabetics compared to normal with no normalising effect with insulin treatment. The AT(1)-receptor density was normalised in the diabetic groups treated with losartan +/- insulin. Results for AT(2)-receptor regulation revealed a significant difference between untreated (D) and losartan-treated (DL, DIL) diabetic groups. All of these data show the interrelated pathway and cross-talk between insulin and Ang II system indicating potentially negative effects on the diabetic heart.

  14. Intermittent fasting modulation of the diabetic syndrome in sand rats. II. In vivo investigations.

    PubMed

    Belkacemi, Louiza; Selselet-Attou, Ghalem; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J

    2010-11-01

    This study deals with the effects of daily intermittent fasting for 15 h upon the development of diabetes in sand rats exposed to a hypercaloric diet. The same pattern of daily intermittent fasting was imposed on sand rats maintained on a purely vegetal diet (control animals). Over the last 30 days of the present experiments, non-fasting animals gained weight, whilst intermittently fasting sand rats lost weight. In this respect, there was no significant difference between control animals and either diabetic or non-diabetic sand rats exposed to the hypercaloric diet. The postprandial glycemia remained fairly stable in the control animals. During a 3-week transition period from a purely vegetal to a hypercaloric diet, the post-prandial glycemia increased by 5.95 ± 1.26 mM (n=6) in diabetic sand rats, as distinct from an increase of only 0.45 ± 0.56 mM (n=6) in the non-diabetic animals. During the intermittent fasting period, the postprandial glycemia decreased significantly in the diabetic animals, but not so in the non-diabetic sand rats. Before the switch in food intake, the peak glycemia at the 30th min of an intraperitoneal glucose tolerance test was already higher in the diabetic than non-diabetic rats. In both the non-diabetic and diabetic sand rats, intermittent fasting prevented the progressive deterioration of glucose tolerance otherwise observed in non-fasting animals. These findings reveal that, at least in sand rats, intermittent daily fasting prevents the progressive deterioration of glucose tolerance otherwise taking place when these animals are exposed to a hypercaloric diet.

  15. Antioxidant icariside II combined with insulin restores erectile function in streptozotocin-induced type 1 diabetic rats.

    PubMed

    Wang, Lin; Xu, Yongde; Li, Huixi; Lei, Hongen; Guan, Ruili; Gao, Zhezhu; Xin, Zhongcheng

    2015-05-01

    Erectile dysfunction (ED) worsens in patients with diabetes mellitus (DM) despite good control of blood glucose level with insulin. Recent studies imply that diabetic vascular stresses (e.g. oxidative stress) persist in spite of glucose normalization, which is defined as metabolic memory. Studies suggest that the interaction between advanced glycation end products (AGEs) and their receptor (RAGE) mediates the development of metabolic memory. To investigate the effects of the antioxidant icariside II plus insulin on erectile function in streptozotocin (STZ)- induced type 1 diabetic rats. Fifty 8-week-old Sprague-Dawley rats were randomly distributed into five groups: normal control, diabetic, insulin-treated diabetic, icariside II-treated diabetic, and insulin plus icariside II-treated diabetic. Diabetes was induced by a single intraperitoneal injection of STZ. Eight weeks after induction of diabetes, icariside II was administered by gastric lavage once a day (5 mg/kg) for 6 weeks; and 2-6 units of intermediate-acting insulin were given to maintain normal glycemia for 6 weeks. The main outcome measures were the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP); histology of penile endothelial cells and smooth muscle cells; neural nitric oxide synthase, AGEs and RAGE expression; malondialdehyde concentration; superoxide dismutase activity; and apoptosis index. Diabetic rats demonstrated a significantly lower ICP/MAP ratio, reduced penile endothelial cells, reduced smooth muscle cells, increased AGEs and RAGE, and increased apoptosis. Insulin and icariside II monotherapy partially restored erectile function and histological changes. However, the combination therapy group showed significantly better erectile parameters, cytological components and biochemistry, similar to those in the normal control group. These results suggest that, although insulin can effectively control glycemic levels, it does not completely alter the pathological changes in

  16. Strict angiotensin blockade prevents the augmentation of intrarenal angiotensin II and podocyte abnormalities in type 2 diabetic rats with microalbuminuria

    PubMed Central

    Nishiyama, Akira; Nakagawa, Toshitaka; Kobori, Hiroyuki; Nagai, Yukiko; Okada, Noriyuki; Konishi, Yoshio; Morikawa, Takashi; Okumura, Michiaki; Meda, Isseiki; Kiyomoto, Hideyasu; Hosomi, Naohisa; Mori, Takefumi; Ito, Sadayoshi; Imanishi, Masahito

    2008-01-01

    Objectives Beneficial effects of angiotensin II type 1 receptor blockers have been indicated for patients with diabetic nephropathy. We investigated the effects of an angiotensin II type 1 receptor blocker, telmisartan, on intrarenal angiotensin II levels and the progression of albuminuria or glomerular injury in type 2 diabetic Otsuka Long–Evans Tokushima Fatty rats with microalbuminuria. Methods and Results Otsuka Long–Evans Tokushima Fatty rats were randomly treated with telmisartan (10 mg/kg/day, orally), hydralazine (25 mg/kg/day in drinking water) or vehicle from the initiation of albuminuria (13 weeks old). At this age, Otsuka Long–Evans Tokushima Fatty rats showed low but detectable albuminuria (1.0±0.1 mg/day) and higher systolic blood pressure, postprandial blood glucose and kidney angiotensin II levels than age-matched nondiabetic Long–Evans Tokushima Otsuka rats. At 35 weeks of age, vehicle-treated Otsuka Long–Evans Tokushima Fatty rats did not show apparent glomerular injury or tubulointerstitial fibrosis but did exhibit severe albuminuria (72.6±5.9 mg/day) and accumulation of cytoplasmic granules containing albumin in podocytes. Otsuka Long–Evans Tokushima Fatty rats also showed higher systolic blood pressure, postprandial blood glucose, collagen gene expression, desmin staining (a marker of podocyte injury) and angiotensin II levels than Long–Evans Tokushima Otsuka rats. Treatment with telmisartan did not affect postprandial blood glucose but decreased systolic blood pressure, collagen gene expression, desmin staining and angiotensin II levels. Telmisartan also prevented the development of albuminuria (0.6±0.1 mg/day at 35 weeks old) and accumulation of cytoplasmic granules. Hydralazine treatment resulted in a similar reduction in systolic blood pressure and partially attenuated the albuminuria (35.4±1.8 mg/day at 35 weeks old) but did not affect the other parameters. Conclusion The present results suggest the contribution of

  17. Green Tea Attenuates Oxidative Stress and Downregulates the Expression of Angiotensin II AT1 Receptor in Renal and Hepatic Tissues of Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Thomson, Martha; Al-Qattan, Khaled; Mansour, Mohamed H.; Ali, Muslim

    2012-01-01

    This study investigates the potential of green tea to modulate oxidative stress and angiotensin II AT1 receptor expression in renal and hepatic tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (diabetic control), and green-tea-treated diabetic rats. Total antioxidant, catalase, and malondialdehyde levels were assayed by standard procedures. Levels of AT1 receptor labeling, in renal and hepatic tissues of the three rat groups, were immunohistochemically investigated using an anti-AT1 receptor antibody. Levels of total antioxidant and catalase were significantly reduced, whereas malondialdehyde levels and AT1 receptor labeling were significantly increased in renal and hepatic tissues of diabetic control rats compared to normal rats. Compared to diabetic control rats, total antioxidant and catalase levels were significantly increased, whereas malondialdehyde levels and AT1 receptor labeling in the green-tea-treated diabetic group were significantly reduced throughout hepatic lobules and renal cortical and medullary vascular and tubular segments to levels comparable to those observed in normal rats. The capacity of green tea to modulate diabetes-induced oxidative stress and AT1 receptor upregulation may be beneficial in opposing the deleterious effects of excessive angiotensin II signaling, manifested by progressive renal and hepatic tissue damage. PMID:23243444

  18. Synthesis, characterization, and efficacy evaluation of a new anti-diabetic vanadyl(II) thiamine hydrochloride complex in streptozotocin-induced diabetic rats.

    PubMed

    Ahmed El-Shazly, Samir; Ahmed, Mohamed Mohamed; Ibrahim, Zein Shaban; Refat, Moamen S

    2015-06-01

    Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to abnormalities in either insulin secretion or action. A range of vanadium complexes have been synthesized and demonstrated to be effective in lowering hyperglycemia. Thiamine administration was also reported to prevent deterioration in fasting glucose and insulin levels, and to improve glucose tolerance in hyperglycemic patients. This study has been conducted to evaluate the ionic vanadyl(II) thiamine hydrochloride complex (VC) as a new anti-diabetic candidate. The new complex was characterized by infrared spectroscopy (FT-IR), electronic spectra, magnetic susceptibility, electron spin resonance (ESR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The anti-diabetic effect of VC was investigated in comparison to vanadium sulfate in streptozotocin (STZ)-induced diabetic rats. Treatment of diabetic rats with VC versus vanadyl sulfate showed a more potent effect on reducing serum glucose and cholesterol close to normal levels. VC suppressed the diabetes-induced upregulation of hepatic glucose transporter (GLUT)-2, Phosphoenol pyruvate carboxykinase (PEPCK), and hormone-sensitive lipase (HSL) more significantly than vanadyl sulfate. Either vanadyl sulfate or VC restored hepatic sterol regulatory element-binding protein transcription factor-1c (SREBP-1c) and muscle hexokinase (HK) mRNA expression that was downregulated in diabetic group. Pyruvate kinase (PK) mRNA expression was restored more significantly in VC-treated than vanadyl sulfate-treated diabetic rats. These results indicate that the newly synthesized VC could be an effective anti-diabetic candidate as the anti-diabetic activity of the ionic vanadium was enhanced after being modified with the organic ligand, thiamin. The results also suggest that VC achieves its effect most likely through modulating the transcription of energy metabolizing enzymes. © The Author(s) 2015.

  19. Curcumin Inhibits Neuronal Loss in the Retina and Elevates Ca2+/Calmodulin-Dependent Protein Kinase II Activity in Diabetic Rats

    PubMed Central

    Wang, Peipei; Zhu, Yanxia; Chen, Zhen; Shi, Tianyan; Lei, Wensheng

    2015-01-01

    Abstract Purpose: To determine whether curcumin offers neuroprotection to minimize the apoptosis of neural cells in the retina of diabetic rats. Methods: Streptozotocin (STZ)-induced diabetic rats and control rats were used in this study. A subgroup of STZ-induced diabetic rats were treated with curcumin for 12 weeks. Retinal histology, apoptosis of neural cells in the retina, electroretinograms, and retinal glutamate content were evaluated after 12 weeks. Retinal levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII), phospho-CaMKII (p-CaMKII), and cleaved caspase-3 were determined by Western blot analysis. Results: The amplitudes a-wave, b-wave, and oscillatory potential were reduced by diabetes, but curcumin treatment suppressed this reduction of amplitudes. Curcumin also prevented cell loss from the outer nuclear, inner nuclear, and ganglion cell layers. Apoptosis of retinal neurons was detected in diabetic rats. The concentration of glutamate in the retina was higher in diabetic rats, but was significantly reduced in the curcumin-treated group. Furthermore, p-CaMKII and cleaved caspase-3 expression were upregulated in the diabetic retina, but reduced in curcumin-treated rats. Conclusions: Curcumin attenuated diabetes-induced apoptosis in retinal neurons by reducing the glutamate level and downregulating CaMKII. Thus, curcumin might be used to prevent neuronal damage in the retina of patients with diabetes mellitus. PMID:26207889

  20. Anti-diabetic effects of aqueous prickly lettuce (Lactuca scariola Linn.) leaves extract in alloxan-induced male diabetic rats treated with nickel (II).

    PubMed

    Chadchan, Kailash S; Jargar, Jameel G; Das, Swastika N

    2016-01-01

    Hattaraki pallye or prickly lettuce (Lactuca scariola Linn.) is one among several green leafy plants that grow in north Karnataka; it is usually consumed by the people of this region and is found to be antidiabetic in nature. The objective of this study is to evaluate hypoglycemic activities of supplementation with aqueous extract of prickly lettuce (L. scariola) leaves in vivo in acute and subchronic exposure with or without nickel (II) along with its glucose reduction capabilities with or without nickel (II) at pH 7.0 and 9.0 in vitro. Percentage glucose reduction (in vitro) was determined by glucose oxidase-peroxidase enzymatic method at pH 7.0 and pH 9.0 using UV-Vis spectrophotometer. Hypoglycemic activities of L. scariola were carried out in alloxan-induced male diabetic rats at both acute and subchronic exposure. The results showed a significant alteration in the λmax value of Ni (II) in combination with L. scariola leaves extracts at both pH 7.0 and 9.0. The aqueous extract also produced a significant reduction in the glucose concentration at pH 7.0 and pH 9.0 even in presence of Ni (II) in vitro. Lactuca scariola leaves in either acute or subchronic supplementation showed a greater glucose tolerance and hypoglycemic regulation of blood sugar in diabetic rats with or without nickel (II) treatments. Lactuca scariola leaves can be a substitute for synthetic drugs to treat diabetic patients.

  1. Angiotensin II receptor blocker telmisartan prevents new-onset diabetes in pre-diabetes OLETF rats on a high-fat diet: evidence of anti-diabetes action.

    PubMed

    Zhao, Zi-Qin; Luo, Rong; Li, Lan-Ying; Tian, Feng-Shi; Zheng, Xi-Lan; Xiong, Hai-Liang; Sun, Li-Ting

    2013-06-01

    This study aims to investigate the effects of telmisartan, pioglitazone and metformin administration on the prevention of new-onset type 2 diabetes mellitus in pre-diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats fed with a high-fat diet (HFD). OLETF rats 22 weeks of age were treated with pioglitazone (O-P), metformin (O-M), telmisartan (O-T) and low telmisartan starting from their pre-diabetes period. The weight, glucose tolerance and insulin sensitivity were measured. The lipid profiles were obtained. The abdominal subcutaneous (SC) and omental (OM) fat pads were dissected to measure the expression of mRNA and protein levels (adiponectin, proinflammatory cytokines, etc.). Telmisartan significantly reversed glucose tolerance and improved insulin resistance. The incidence rates of impaired glucose tolerance and type 2 diabetes in the O-P (χ(2) = 11.025, p=0.001) and O-T (χ(2)=5.495, p=0.019) groups were significantly reduced. The mRNA expression of proinflammatory cytokines was downregulated by telmisartan. The expression of adiponectin, PPARγ1 and γ2 was markedly improved by telmisartan and pioglitazone compared with the OLETF control (O-C) group. The correlation analysis showed that the systolic and diastolic blood pressures were not correlated with the homeostasis model assessment-insulin resistance (p>0.05). Telmisartan acts beneficially against diabetes-induced inflammation and improves insulin resistance in pre-diabetes OLETF rats fed with HFD. In view of this improved responsiveness to insulin sensitivity, telmisartan may prove to be a promising candidate for the intervention treatment of the pre-diabetes state. Copyright © 2013 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  2. Tanshinone II Aattenuates renal damage in STZ-induced diabetic rats via inhibiting oxidative stress and inflammation

    PubMed Central

    Gao, Yu; Sun, Dandan; Liu, Qizhen; Dai, Dongjun; Lu, Zeyuan; Wang, Niansong; Ge, Sheng; Wang, Feng

    2017-01-01

    Oxidative stress and inflammation have been demonstrated to be involved in the onset and promotion of diabetic nephropathy (DN).Tanshinone IIA (Tan) possesses both antioxidant and anti-inflammatory properties. Here, the aim of the present study was to explore whether Tan could attenuate renal damage in the rats with streptozotocin (STZ)-induced diabetes and its potential mechanisms. Tan was gavaged to STZ-induced diabetic rats at the dose of 10mg/kg once a day for 12 weeks. Tan treatment significantly attenuated albuminuria and renal histopathology in diabetic rats. Besides, Tan treatment also effectively inhibited oxidative stress and inflammatory reaction in the kidneys of diabetic rats. Our study provided evidence that the protective effect of Tan on diabetes-induced renal injury is associated with inhibition of oxidative stress and inflammation. Tan may be a potential candidate for the treatment of DN. PMID:28404881

  3. Diabetes mellitus affects activity of calcium/calmodulin-dependent protein kinase II alpha in rat trigeminal ganglia.

    PubMed

    Jerić, Milka; Vuica, Ana; Borić, Matija; Puljak, Livia; Jeličić Kadić, Antonia; Grković, Ivica; Filipović, Natalija

    2015-01-01

    The activity of calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) may play a critical role in the modulation of nociceptor activity and plasticity of primary sensory trigeminal neurons. The aim of this study was to investigate the immunoreactivity of phosphorylated CaMKIIα (pCaMKIIα) in subpopulations of trigeminal ganglion (TG) neurons in rat models of early diabetes type 1 (dm1) and 2 (dm2). DM1 model was induced with intraperitoneally (i.p.) injected streptozotocin (STZ) (55mg/kg). DM2 rats were fed with the high fat diet (HFD) for 2 weeks and then received 35mg/kg of STZ i.p. Two weeks and 2 months after the STZ-diabetes induction, rats were sacrificed and immunohistochemical analysis for detection of pCaMKIIα immunoreactivity and double immunofluorescence labelling with isolectin (IB4) was performed. Increased intensity of pCaMKIIα immunofluorescence, restricted to IB4-negative small-diameter neurons, was seen in TG neurons two months after STZ-DM1 induction. DM1 model, as well as the obesity (control dm2 groups) resulted in neuronal impaired growth while dm2 model led to neuron hypertrophy in TG. Observed changes may play a critical role in the modulation of nociceptor activity and plasticity of primary sensory trigeminal neurons. In future, innovative strategies for modulation of CaMKIIα activity in specific subpopulations of neurons could be a novel approach in therapy of diabetic trigeminal neuropathy. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Antidiabetic activity of alkaloids of Aerva lanata roots on streptozotocin-nicotinamide induced type-II diabetes in rats.

    PubMed

    Agrawal, Ritesh; Sethiya, Neeraj K; Mishra, S H

    2013-05-01

    The roots of Aerva lanata Linn. (Amaranthaceae) (AL) are employed traditionally as an antihyperglycaemic in the Ayurvedic system of medicine. The present investigation is focus for identification and isolation of the bioactive compound from methanol roots extract of AL against streptozocin-nicotinamide induced elevated serum glucose level in rats. The methanol extract of the roots was fractionated using different solvents. The partially purified alkaloid basified toluene fraction (PPABTF) showed the presence of alkaloids. The fraction (10 and 20 mg/kg) was tested for oral glucose tolerance test (OGTT) and in non-insulin-dependent diabetes mellitus (NIDDM)-induced elevated serum glucose level in rats. The fraction was also subjected to high performance thin layer chromatography (HPTLC) for the determination of content of individual alkaloids. Single oral administration of PPABTF (10 and 20 mg/kg) after 20 h caused a significant (p < 0.01) reduction in the serum glucose level (mg/dl). On other hand, PPABTF normalised plasma glucose levels after 2 weeks of repeated oral administration in diabetic rats (p < 0.01). HPTLC analysis on PPABTF showed the presence of three known alkaloids. The fraction was further subjected to column chromatography and the compounds identified by ultraviolet, infrared, mass spectroscopy and nuclear magnetic resonance, as canthin-6-one derivatives. The PPABTF in the dose of 20 mg/kg showed significant effects on streptozotocin-nicotinamide induced type-II NIDDM in rats. The activity may be due to the presence of alkaloids like canthin-6-one derivatives.

  5. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

    EPA Science Inventory

    Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

  6. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

    EPA Science Inventory

    Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

  7. Changes in protein and gene expression of angiotensin II receptors (AT1 and AT2) in aorta of diabetic and hypertensive rats.

    PubMed

    Romero-Nava, R; Rodriguez, J E; Reséndiz-Albor, A A; Sánchez-Muñoz, F; Ruiz-Hernandéz, A; Huang, F; Hong, E; Villafaña, S

    2016-01-01

    Diabetes and hypertension have been associated with cardiovascular diseases and stroke. Some reports have related the coexistence of hypertension and diabetes with increase in the risk of developing vascular complications. Recently some studies have shown results suggesting that in the early stages of diabetes and hypertension exist a reduced functional response to vasopressor agents like angiotensin II (Ang II), which plays an important role in blood pressure regulation mechanism through the activation of its AT1 and AT2 receptors. For that reason, the aim of this work was to study the gene and protein expression of AT1 and AT2 receptors in aorta of diabetic SHR and WKY rats. Diabetes was induced by the administration of streptozotocin (60 mg/kg i.p.). After 4 weeks of the onset of diabetes, the protein expression was obtained by western blot and the mRNA expression by RT-PCR. Our results showed that the hypertensive rats have a higher mRNA and protein expression of AT1 receptors than normotensive rats while the AT2 expression remained unchanged. On the other hand, the combination of diabetes and hypertension increased the mRNA and protein expression of AT1 and AT2 receptors significantly. In conclusion, our results suggest that diabetes with hypertension modifies the mRNA and protein expression of AT1 and AT2 receptors. However, the overexpression of AT2 could be associated with the reduction in the response to Ang II in the early stage of diabetes.

  8. Diabetes-induced alterations in tissue collagen and carboxymethyllysine in rat kidneys: Association with increased collagen-degrading proteinases and amelioration by Cu(II)-selective chelation.

    PubMed

    Brings, Sebastian; Zhang, Shaoping; Choong, Yee S; Hogl, Sebastian; Middleditch, Martin; Kamalov, Meder; Brimble, Margaret A; Gong, Deming; Cooper, Garth J S

    2015-08-01

    Advanced glycation end-products (AGEs) comprise a group of non-enzymatic post-translational modifications of proteins and are elevated in diabetic tissues. AGE-modification impairs the digestibility of collagen in vitro but little is known about its relation to collagen-degrading proteinases in vivo. N(ε)-carboxymethyllysine (CML) is a stable AGE that forms on lysyl side-chains in the presence of glucose, probably via a transition metal-catalysed mechanism. Here, rats with streptozotocin-induced diabetes and non-diabetic controls were treated for 8weeks with placebo or the Cu(II)-selective chelator, triethylenetetramine (TETA), commencing 8weeks after disease induction. Actions of diabetes and drug treatment were measured on collagen and collagen-degrading proteinases in kidney tissue. The digestibility and CML content of collagen, and corresponding levels of mRNAs and collagen, were related to changes in collagen-degrading-proteinases. Collagen-degrading proteinases, cathepsin L (CTSL) and matrix metalloproteinase-2 (MMP-2) were increased in diabetic rats. CTSL-levels correlated strongly and positively with increased collagen-CML levels and inversely with decreased collagen digestibility in diabetes. The collagen-rich mesangium displayed a strong increase of CTSL in diabetes. TETA treatment normalised kidney collagen content and partially normalised levels of CML and CTSL. These data provide evidence for an adaptive proteinase response in diabetic kidneys, affected by excessive collagen-CML formation and decreased collagen digestibility. The normalisation of collagen and partial normalisation of CML- and CTSL-levels by TETA treatment supports the involvement of Cu(II) in CML formation and altered collagen metabolism in diabetic kidneys. Cu(II)-chelation by TETA may represent a treatment option to rectify collagen metabolism in diabetes independent of alterations in blood glucose levels.

  9. Effects of traditional Chinese medicine on rats with Type II diabetes induced by high-fat diet and streptozotocin: a urine metabonomic study.

    PubMed

    Zhao, Huihui; Li, Zhigeng; Tian, Guihua; Gao, Kuo; Li, Zhiyong; Zhao, Baosheng; Wang, Juan; Luo, Liangtao; Pan, Qiu; Zhang, Wenting; Wu, Zhiqian; Chen, Jianxin; Wang, Wei

    2013-09-01

    Type II diabetes has become a serious threat to human health in recent years. Among adults above 20 years old in China, the prevalence rate of diabetes is 9.7%. Thus, it is imperative to study the mechanisms underlying type II diabetes to develop effective therapeutic treatments. To examine metabolic changes in a rat model of type II diabetes and explore mechanisms underlying the beneficial effects of traditional Chinese medicine (TCM) in this model. 120 rats were divided into four groups, including a control group, a high-fat diet group (high-fat diet and streptozotocin injection), a TCM group (high-fat diet, streptozotocin injection, followed by TCM administration), and a rosiglitazone maleate group (high-fat diet, streptozotocin injection, followed by rosiglitazone maleate administration). Metabolites in urine samples from 1-3 weeks (time point 1) and 4-6 weeks (time point 2) of drug administration were compared by gas chromatography-mass spectrometry (GC-MS). Our results showed that in the high-fat diet group, at time point 2, the levels of dihydroxybenzoic acid, L-ascorbic acid, D-gluconic acid, octadecanoic acid, and glutaric acid in urine were significantly higher than at time point 1. In the TCM group, at time point 2, the urine levels of L-ascorbic acid were markedly lower than at time point 1. Our studies demonstrated that examining urine metabolic changes provided important insights into the mechanisms underlying type II diabetes as well as the therapeutic effects of TCM.

  10. The calcium channel antagonist benidipine reduces plasma and cardiac endothelin-1 levels in type II diabetic rat model.

    PubMed

    Jesmin, Subrina; Sakuma, Ichiro; Hattori, Yuichi; Kitabatake, Akira; Miyauchi, Takashi

    2004-11-01

    Cardiovascular complications are the central feature of type 2 diabetes mellitus, and insulin resistance is an early clinical manifestation of type 2 diabetes mellitus. Calcium channel blockers are widely used to treat cardiovascular diseases in diabetic patients; however, it remains unknown how endothelin-1 (ET-1) is altered and associated with cardiac lesions at the insulin-resistant early stage of type 2 diabetes mellitus, and, if so, whether calcium channel blockers can reverse such alterations. We examined plasma and cardiac expression of ET-1 in male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a spontaneous model of human type 2 diabetes mellitus. At 8 weeks of age, OLETF rats were treated for 12 weeks with a long acting calcium channel blocker, benidipine (3 mg/kg per day p.o.) (BEN, n = 15), or with vehicle (OLETF, n = 15), and age-matched genetic control, male Long-Evans Tokushima Otsuka (LETO) rats were also used (n = 15). Blood pressure was significantly higher in OLETF than LETO rats, and benidipine treatment of OLETF rats for 12 weeks did not reduce their blood pressure significantly. Plasma and cardiac levels of ET-1 were significantly higher in OLETF compared with LETO rats (both P < 0.01), and were reversed after benidipine treatment. Our results suggest that ET-1 plays a pivotal role in the pathogenesis of cardiac complications at the insulin-resistant stage of diabetes mellitus, and that benidipine treatment may have a beneficial effect on these complications.

  11. Effect of des-aspartate-angiotensin I on the actions of angiotensin II in the isolated renal and mesenteric vasculature of hypertensive and STZ-induced diabetic rats.

    PubMed

    Dharmani, M; Mustafa, M R; Achike, F I; Sim, M K

    2005-07-15

    The present study investigated the action of des-aspartate-angiotensin I (DAA-I) on the pressor action of angiotensin II in the renal and mesenteric vasculature of WKY, SHR and streptozotocin (STZ)-induced diabetic rats. Angiotensin II-induced a dose-dependent pressor response in the renal vasculature. Compared to the WKY, the pressor response was enhanced in the SHR and reduced in the STZ-induced diabetic rat. DAA-I attenuated the angiotensin II pressor action in renal vasculature of WKY and SHR. The attenuation was observed for DAA-I concentration as low as 10(-18) M and was more prominent in SHR. However, the ability of DAA-I to reduce angiotensin II response was lost in the STZ-induced diabetic kidney. Instead, enhancement of angiotensin II pressor response was seen at the lower doses of the octapeptide. The effect of DAA-I was not inhibited by PD123319, an AT2 receptor antagonist, and indomethacin, a cyclo-oxygenase inhibitor in both WKY and SHR, indicating that its action was not mediated by angiotensin AT2 receptor and prostaglandins. The pressor responses to angiotensin II in mesenteric vascular bed were also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses were significantly smaller in SHR but no significant difference was observed between STZ-induced diabetic and WKY rat. Similarly, PD123319 and indomethacin had no effect on the action of DAA-I. The findings reiterate a regulatory role for DAA-I in vascular bed of the kidney and mesentery. By being active at circulating level, DAA-I subserves a physiological role. This function appears to be present in animals with diseased state of hypertension and diabetes. It is likely that DAA-I functions are modified to accommodate the ongoing vascular remodeling.

  12. Identification of T cell subsets and class I and class II antigen expression in islet grafts and pancreatic islets of diabetic BioBreeding/Worcester rats.

    PubMed Central

    Weringer, E. J.; Like, A. A.

    1988-01-01

    The BioBreeding/Worcester (BB/Wor) rat develops a spontaneous disorder that closely resembles human insulin-dependent (Type I) diabetes mellitus. The syndrome is preceded by lymphocytic insulitis that destroys pancreatic beta cells. The morphologic features of the spontaneous insulitis lesions are also observed within islets transplanted beneath the renal capsule of diabetes-prone and diabetic animals. This study reports the results of experiments in which immunohistochemical techniques were used to characterize the phenotype of the infiltrating mononuclear cells and detect the expression of class I and class II MHC antigens in native islets and islet transplants in diabetic and diabetes-prone BB/Wor rats. The infiltrates within native pancreatic islets and islet grafts were comprised predominantly of Ia+ cells (dendritic cells and macrophages) CD4+ cells (helper/inducer lymphocytes and macrophages), CD5+ (pan-T) cells and smaller numbers of CD8+ (cytotoxic/suppressor and NK) cells. Pancreatic and graft insulitis were accompanied by markedly enhanced class I antigen expression on islet and exocrine cells. Class II (Ia) antigens were not detected on normal islet cells, islets undergoing insulitis or on islet transplants subjected to immune attack. In islet grafts stained with polymorphic MAbs that distinguish Ia antigens of donor and host origin, Ia antigen expression was limited to infiltrating dendritic cells and macrophages of host origin. It is concluded that the phenotypes of infiltrating mononuclear cells that comprise the insulitis lesion in spontaneous BB/Wor diabetes, and the inflammatory attack on islets transplanted into diabetic BB/Wor rats are the same, that pancreatic islet and graft insulitis occur in the presence of enhanced class I antigen expression but in the absence of class II antigen expression, and that infiltrating Ia+ cells within islet grafts are exclusively of recipient (BB/Wor) origin and may explain the initiation of immune insulitis

  13. Quantitative proteomic profiling identifies new renal targets of copper(II)-selective chelation in the reversal of diabetic nephropathy in rats.

    PubMed

    Gong, Deming; Chen, Xiuyin; Middleditch, Martin; Huang, Liangdong; Vazhoor Amarsingh, Greeshma; Reddy, Shiva; Lu, Jun; Zhang, Shaoping; Ruggiero, Katya; Phillips, Anthony R J; Cooper, Garth J S

    2009-09-01

    This study aimed to identify new diabetic nephropathy (DN)-related proteins and renal targets of the copper(II)-selective chelator, triethylenetetramine (TETA) in streptozotocin-diabetic rats. We used the recently developed iTRAQ technology to compare renal protein profiles among non-diabetic, diabetic, and TETA-treated diabetic rats. In diabetic kidneys, tubulointerstitial nephritis antigen (TINag), voltage-dependent anion-selective channel (VDAC) 1, and VDAC2 were up-regulated in parallel with alterations in expression of proteins with functions in oxidative stress and oxidative phosphorylation (OxPhos) pathways. By contrast, mitochondrial HSP 60, Cu/Zn-superoxide dismutase, glutathione S-transferase alpha3 and aquaporin-1 were down-regulated in diabetic kidneys. Following TETA treatment, levels of D-amino acid oxidase-1, epoxide hydrolase-1, aquaporin-1, and a number of mitochondrial proteins were normalized, with concomitant amelioration of albuminuria. Changes in levels of TINag, collagen VIalpha1, actinin 4alpha, apoptosis-inducing factor 1, cytochrome C, histone H3, VDAC1, and aquaporin-1 were confirmed by Western blotting or immunohistochemistry. Changes in expression of proteins related to tubulointerstitial function, podocyte structure, and mitochondrial apoptosis are implicated in the mechanism of DN and their reversal by TETA. These findings are consistent with the hypothesis that this new experimental therapy may be useful for treatment of DN.

  14. Heart failure progression is accelerated following myocardial infarction in type II diabetic rats

    USDA-ARS?s Scientific Manuscript database

    Clinical studies have shown a greater incidence of myocardial infarction in diabetic patients and following an infarction, diabetes is associated with an increased risk for the development of left ventricular dysfunction and heart failure. The goal of this study was to determine if the progression o...

  15. Garlic Attenuates Plasma and Kidney ACE-1 and AngII Modulations in Early Streptozotocin-Induced Diabetic Rats: Renal Clearance and Blood Pressure Implications

    PubMed Central

    Al-Qattan, Khaled K.; Jayasree, Divya; Ali, Muslim

    2016-01-01

    Raw garlic aqueous extract (GE) has ameliorative actions on the renin-angiotensin system in type-1 diabetes mellitus (DM); however its effects on plasma and kidney angiotensin I converting enzyme type-1 (ACE-1) and angiotensin II (AngII) require further elucidation. This study investigated the effect of GE on plasma and kidney ACE-1 and AngII concentrations and in relation to systemic and renal clearance indicators significant to blood pressure (BP) homeostasis in early streptozotocin- (STZ-) induced type-1 DM. Normal rats (n = 10) received 0.5 mL normal saline (NR/NS), diabetic rats (n = 10) received 0.5 mL NS (DR/NS), and treated diabetic rats (n = 10) received 50 mg/0.1 mL/100 g body weight GE (DR/GE) as daily intraperitoneal injections for 8 weeks. Compared to NR/NS, DR/NS showed a significant increase in plasma ACE-1 and AngII and conversely a decrease in kidney ACE-1 and AngII. These changes were associated with an increase in BP and clearance functions. Alternatively and compared to DR/NS, DR/GE showed normalization or attenuation in plasma and kidney ACE-1 and AngII. These GE induced rectifications were associated with moderation in BP elevation and renal clearance functions. Garlic attenuates modulations in plasma and kidney ACE-1 and AngII, in addition to BP and renal clearance function in type-1 DM. PMID:27293465

  16. Pancreas transplantation using type I and type II spontaneously diabetic rats--our experimental experience.

    PubMed

    Ito, Toshinori; Shimada, Kazunori; Gang, Miao; Uchikoshi, Fumihiro; Tori, Masayuki; Komoda, Hiroshi; Fumimoto, Yuichi; Ohmori, Ken; Kawamoto, Koichi; Tanemura, Masahiro; Nozawa, Masumi

    2007-01-01

    Pancreas transplantation (PTx) is the only therapy that can cure type 1 diabetes mellitus. With the recent advance of surgical procedures and immunosuppression, the outcome of PTx has become better than it used to be before, but some problems still remain. It is rather difficult to induce tolerance and to reverse rejection once it occurred because pancreas graft itself has a strong immunogenicity. Another important issue is regarding the recurrence of autoimmune disease in the pancreatic graft, therefore, some animal models are necessary to delineate and regulate those immune responses specific for PTx. Recently, PTx is also clinically applicable for type 2 diabetic patients with end-stage renal disease. It has been shown that insulin resistance was improved by PTx in type 2 diabetic recipients. In the current study, we have introduced some useful type 1 and type 2 diabetic models mainly based on our experimental experiences.

  17. Influence of diabetes on plasma pharmacokinetics and brain bioavailability of grape polyphenols and their phase II metabolites in the Zucker diabetic fatty rat.

    PubMed

    Chen, Tzu-Ying; Ferruzzi, Mario G; Wu, Qing-Li; Simon, James E; Talcott, Stephen T; Wang, Jun; Ho, Lap; Todd, George; Cooper, Bruce; Pasinetti, Giulio M; Janle, Elsa M

    2017-10-01

    The effect of diabetes on the pharmacokinetics, bioavailability and brain distribution of grape polyphenols and select metabolites was studied in the Zucker diabetic fatty (ZDF) rat model. (ZDF) rats and their lean controls (LN) were dosed with a Standardized Grape Polyphenol (SGP) Mixture consisting of grape seed extract, Concord grape juice and resveratrol (RES) by oral gavage for 10 days. An 8-h pharmacokinetic study was performed. After 24 h, a second dose of SGP was administered and 1 h later animals were sacrificed and brain tissue was harvested. Plasma, urine, and brain tissue were analyzed for grape polyphenols. ZDF rats exhibited significantly diminished Cmax for all catechin, epicatechin, quercetin and resveratrol conjugated metabolites. Bioavailability was significantly lower in ZDF rats for methylated flavan-3-ol, RES, and quercetin metabolites. Significantly lower levels of metabolites of RES, quercetin, and flavan-3-ols were found in brains of ZDF rats. There was no significant difference between ZDF and LN in anthocyanins in plasma and no anthocyanins were detectable in brain extracts. ZDF rats showed significantly higher urinary excretion for all polyphenols. Diabetes may alter the overall bioavailability of some polyphenols in plasma and brain in part due to higher urinary clearance. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Untargeted serum metabolomics reveals Fu-Zhu-Jiang-Tang tablet and its optimal combination improve an impaired glucose and lipid metabolism in type II diabetic rats.

    PubMed

    Tao, Yi; Chen, Xi; Cai, Hao; Li, Weidong; Cai, Baochang; Chai, Chuan; Di, Liuqing; Shi, Liyun; Hu, Lihong

    2017-01-01

    Fu-Zhu-Jiang-Tang tablet, a six-herb preparation, was proved to show beneficial effects on type II diabetes patients in clinical. This study aims to optimize the component proportion of the six-herb preparation and explore the serum metabolic signatures of type II diabetes rats after treatment with Fu-Zhu-Jiang-Tang tablet and its optimal combination. The component proportion of the preparation was optimized using uniform experimental design and machine learning techniques. Untargeted GC-MS metabolomic experiments were carried out with serum samples from model group and treatment groups. Data were normalized, multivariate and univariate statistical analysis performed and metabolites of interest putatively identified. 23 metabolites were significantly changed by Fu-Zhu-Jiang-Tang tablet treatment and the majority of these were decreased, including various carbohydrates (glucose, mannose, fructose, allose and gluconic acid), unsaturated fatty acids (palmitic acid, 9-octadecenoic acid, oleic acid, arachidonic acid), alanine, valine, propanoic acid, 3-hydroxybutyrate, along with pyrimidine and cholesterol. Increased concentrations of oxalic acid, leucine, glycine, serine, threonine, proline, lysine and citrate were observed. In the optimal combination-fed group, 21 metabolites were significantly affected and strikingly, the magnitudes of changes here were generally much greater than that of Fu-Zhu-Jiang-Tang tablet treated rats. 18 metabolites affected in both groups included various carbohydrates (mannose, glucose, allose, fructose and gluconic acid), unsaturated fatty acids (palmitic acid, 9-octadecenoic acid, oleic acid and arachidonic acid), short-chain fatty acids (oxalic acid, 3-hydroxybutyrate), and amino acids (alanine, valine, leucine, glycine, proline and lysine), as well as pyrimidine. Metabolites exclusively affected in optimal combination treated rat included succinic acid, cysteine and phenylalanine, whilst four metabolites (propanoic acid, citrate

  19. The bioflavonoid quercetin synergises with PPAR-γ agonist pioglitazone in reducing angiotensin-II contractile effect in fructose-streptozotocin induced diabetic rats.

    PubMed

    Kunasegaran, Thubasni; Mustafa, Mohd Rais; Murugan, Dharmani Devi; Achike, Francis I

    2016-06-01

    This study investigated the effects of combined minimal concentrations of quercetin and pioglitazone on angiotensin II-induced contraction of the aorta from fructose-streptozotocin (F-STZ)-induced type 2 diabetic rats and the possible role of superoxide anions (O2(-)) and nitric oxide (NO) in their potential therapeutic interaction. Contractile responses to Ang II of aortic rings from Sprague-Dawley (SD) and F-STZ rats were tested following pre-incubation of the tissues in the vehicle (DMSO; 0.05%), quercetin (Q, 0.1 μM), pioglitazone (P, 0.1 μM) or their combination (P + Q; 0.1 μM each). The amount of superoxide anion was evaluated by lucigenin-enhanced chemiluminescence and dihydroethidium fluorescence, and NO by assay of total nitrate/nitrite, and 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate. The synergistic reduction of Ang II-induced contraction of diabetic but not normal aorta with minimally effective concentrations of P + Q occurs through inhibiting O2(-) and increasing NO bioavailability. This finding opens the possibility of maximal vascular protective/antidiabetic effects with low dose pioglitazone combined with quercetin, thus minimizing the risk of adverse effects.

  20. Leptin and Its Relation to Obesity and Insulin in the SHR/N-corpulent Rat, A Model of Type II Diabetes Mellitus

    PubMed Central

    Bhathena, Sam J.; Hansen, Carl T.

    2001-01-01

    The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic animal model that exhibits obesity, metabolic features of hyperinsulinemia, hyperglycemia, and hyperlipidemia, which are characteristic of type II diabetes and mild hypertension. To determine the role of leptin, the protein product of the ob gene, in the development of obesity and diabetes in this model, we measured steady-state circulating levels of leptin in obese and lean SHR/N-cp rats and examined the relation between plasma leptin levels and metabolic variables at the stage of established obesity in these animals. Mean fasting plasma leptin concentration was 8-fold higher in obese than in lean rats (p<0.01). This was associated with a 6-fold elevation in plasma insulin in the obese group. Fasting levels of plasma glucose, cholesterol, and triglyceride were all significantly higher in obese rats than in lean controls. Spearman correlation analysis showed a significant positive correlation between plasma leptin concentration and body weight among the animals (r=0.73, p<0.01). Similarly, plasma insulin concentration was significantly correlated with BW in all animals (r=0.54, p<0.05). There was also a significant positive.correlation between plasma leptin and plasma insulin in the entire group (r=0.70, p<0.01). However, this relationship was significant only for lean rats but not for obese rats (r=0.59, p<0.05 for lean rats, and r=0.23, p=NS, for obese rats). Plasma leptin also correlated positively with fasting plasma glucose (r=0.75, p<0.05), total cholesterol (r=0.63, p<0.05), and triglyceride (r=0.67, p <0.05). The marked elevation of plasma leptin in obese SHR/N-cp rats suggests that obesity in this animal model is related to up-regulation of the ob gene. Circulating leptin appears to be one of the best biological markers of obesity and that hyperleptinemia is closely associated with several metabolic risk factors related to insulin resistance in the diabesity syndrome. PMID:12369710

  1. Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, mTOR and the NO–cGMP pathway

    PubMed Central

    Zhang, Jian; Li, Ai-Min; Liu, Bao-Xing; Han, Fei; Liu, Feng; Sun, Shao-Peng; Li, Xin; Cui, Shu-Jin; Xian, Shao-Zhong; Kong, Guang-Qi; Xin, Zhong-Cheng; Ji, Zhi-Li

    2013-01-01

    Erectile dysfunction (ED) is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid II. This study investigates the effects of icarisid II on diabetic rats with ED and its potential mechanism via the assessment of advanced glycosylation end products (AGEs), autophagy, mTOR and the NO–cGMP pathway. Icarisid II was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid II group, rats were administered icarisid II intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure (ICP/MAP). AGE concentrations, nitric oxide synthase (NOS) activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 localisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid II increased ICP/MAP values, the smooth muscle cell (SMC) growth curve, S phase and SMC/collagen fibril (SMC/CF) proportions and decreased Beclin 1 (P<0.05). Icarisid II significantly increased the proliferative index and p-p70S6K(Thr389) levels and decreased the numbers of autophagosomes and the levels of LC3-II (P<0.01). Icarisid II decreased AGE concentrations and increased cGMP concentration, NOS activity (P<0.05) and cNOS levels (P<0.01) in the diabetic ED group. Therefore, Icarisid II constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO–cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway. PMID:22728670

  2. An Extended Minimal Physiologically Based Pharmacokinetic Model: Evaluation of Type II Diabetes Mellitus and Diabetic Nephropathy on Human IgG Pharmacokinetics in Rats.

    PubMed

    Chadha, Gurkishan S; Morris, Marilyn E

    2015-11-01

    Although many studies have evaluated the effects of type 2 diabetes mellitus (T2DM) on the pharmacokinetics (PK) of low molecular weight molecules, there is limited information regarding effects on monoclonal antibodies. Our previous studies have reported significant increases in total (2-4 fold) and renal (100-300 fold) clearance of human IgG, an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Pioglitazone treatment incompletely reversed the disease-related PK changes. The objective of this study was to construct a mechanistic model for simultaneous fitting plasma and urine data, to yield physiologically relevant PK parameters. We propose an extended minimal physiologically based PK (mPBPK) model specifically for IgG by classifying organs as either leaky or tight vascular tissues, and adding a kidney compartment. The model incorporates convection as the primary mechanism of IgG movement from plasma into tissues, interstitial fluid (ISF) in extravascular distribution space, and glomerular filtration rate (GFR), sieving coefficient and fraction reabsorbed in the kidney. The model captured the plasma and urine PK profiles well, and simulated concentrations in ISF. The model estimated a 2-4 fold increase in nonrenal clearance from plasma and 30-120 fold increase in renal clearance with T2DM, consistent with the experimental findings, and these differences in renal clearance were related to changes in GFR, sieving coefficient, and proximal tubular reabsorption. In conclusion, the mPBPK model offers a more relevant approach for analyzing plasma and urine IgG concentration-time data than conventional models and provides insight regarding alterations in distributional and elimination parameters occurring with T2DM.

  3. Metallothionein metabolism in the streptozotocin-diabetic rat

    SciTech Connect

    Chen, M.L.; Failla, M.L.

    1986-03-05

    Earlier reports from their laboratory showed the induction of the insulin-deficient diabetic state in adult rats was associated with an accumulation of zinc, copper, and a metallothionein-like zinc and copper binding protein in the soluble fraction of liver and kidney. Based upon chromatographic and electrophoretic properties, -SH to metal ratio and amino acid composition, they now report that elevated concentrations of metallothioneins (MT)-I and -II are indeed present in diabetic rat liver and kidney cytosol. The relative rates of MT synthesis in tissues from diabetic and control rats were measured by comparing incorporation of /sup 35/S-cysteine into MT vs. total cytoplasmic proteins at 5 h after injection of the precursor. The relative rates of MT synthesis in livers from rats diabetic for 10 d and fed either chow or purified diet containing 13 or 35 ppm copper were 1.4, 2.3 and 2.8 times greater, respectively, than control rats fed the same diets. Higher relative rates of MT synthesis were also observed in kidneys from diabetic rats fed purified diets compared to controls. Maximal relative rates of MT synthesis in diabetic liver and kidney were observed at 4 and 10 d, respectively, after onset of diabetes. The half-lives of cytoplasmic MT in liver and kidney from diabetic (10 d) rats were 1.3 and 2.6 days, respectively; half-lives of MT in control liver and kidney were 5.0 and 2.1 days, respectively.

  4. Vascular hypertrophy and albumin permeability in a rat model combining hypertension and diabetes mellitus. Effects of calcium antagonism, angiotensin converting enzyme inhibition, and angiotensin II-AT1-receptor blockade.

    PubMed

    Hulthén, U L; Cao, Z; Rumble, J R; Cooper, M E; Johnston, C I

    1996-09-01

    The aim of this study was to compare the effects of angiotensin converting enzyme (ACE) inhibition, angiotensin II (AII) AT1-receptor blockade, and dihydropyridine calcium antagonism on hypertrophy and on vascular albumin permeability in kidney, heart, and mesenteric artery in a model combining genetic hypertension and diabetes mellitus. Diabetes mellitus was induced by streptozotocin in 8-week-old spontaneously hypertensive rats. The animals were randomized to receive no treatment, the angiotensin converting enzyme inhibitor ramipril, the AII AT1-receptor blocker valsartan, or the dihydropyridine calcium antagonist lacidipine for 3 weeks. Vascular albumin permeability was measured as the tissue content of intravenously injected Evans blue dye (EB) in kidney, heart, and mesenteric artery and the tissue/plasma EB ratio was calculated. Systolic blood pressure was reduced by all three antihypertensive regimens. Glycemic control was similar in all diabetic groups. Kidney hypertrophy was not affected by any of the antihypertensive drugs. Hypertrophy of the mesenteric artery was enhanced by lacidipine but was not affected by ramipril or valsartan. Relative heart weight was also increased by lacidipine. Vascular albumin permeability, expressed as EB content in micrograms/gram dry weight or as tissue/plasma EB ratio, was higher in the kidneys of lacidipine-treated rats than in any other group of diabetic rats. There was a positive correlation between kidney weight/body weight and kidney/plasma EB ratio in the diabetic rats. These findings indicate that the dihydropyridine calcium antagonist lacidipine is associated with an unfavorable effect on vascular hypertrophy and on vascular albumin permeability in the kidneys in rats with hypertension and diabetes mellitus. Furthermore, there seems to be a coupling in the diabetic kidney between hypertrophy and increased vascular albumin permeability.

  5. Quercetin-Rich Guava (Psidium guajava) Juice in Combination with Trehalose Reduces Autophagy, Apoptosis and Pyroptosis Formation in the Kidney and Pancreas of Type II Diabetic Rats.

    PubMed

    Lin, Chia-Fa; Kuo, Yen-Ting; Chen, Tsung-Ying; Chien, Chiang-Ting

    2016-03-10

    We explored whether the combination of anti-oxidant and anti-inflammatory guava (Psidium guajava) and trehalose treatment protects the kidney and pancreas against Type II diabetes (T2DM)-induced injury in rats. We measured the active component of guava juice by HPLC analysis. T2DM was induced in Wistar rats by intraperitoneal administration of nicotinamide and streptozotocin and combination with high fructose diets for 8 weeks. The rats fed with different dosages of guava juice in combination with or without trehalose for 4 weeks were evaluated the parameters including OGTT, plasma insulin, HbA1c, HOMA-IR (insulin resistance) and HOMA-β (β cell function and insulin secretion). We measured oxidative and inflammatory degrees by immunohistochemistry stain, fluorescent stain, and western blot and serum and kidney reactive oxygen species (ROS) by a chemiluminescence analyzer. High content of quercetin in the guava juice scavenged H2O2 and HOCl, whereas trehalose selectively reduced H2O2, not HOCl. T2DM affected the levels in OGTT, plasma insulin, HbA1c, HOMA-IR and HOMA-β, whereas these T2DM-altered parameters, except HbA1c, were significantly improved by guava and trehalose treatment. The levels of T2DM-enhanced renal ROS, 4-hydroxynonenal, caspase-3/apoptosis, LC3-B/autophagy and IL-1β/pyroptosis were significantly decreased by guava juice and trehalose. The combination with trehalose and guava juice protects the pancreas and kidney against T2DM-induced injury.

  6. Expression and localization of the AT1 and AT2 angiotensin II receptors and α1A and α1D adrenergic receptors in aorta of hypertensive and diabetic rats.

    PubMed

    Rodríguez, Jessica Edith; Romero-Nava, Rodrigo; Reséndiz-Albor, Aldo Arturo; Rosales-Cruz, Erika; Hong, Enrique; Huang, Fengyang; Villafaña, Santiago

    2017-01-01

    Hypertension and diabetes are multifactorial diseases that frequently coexist and exacerbate each another. During the development of diabetes, the impairment of noradrenergic and renin-angiotensin systems has been reported in the response mediated by α1-AR and AT1 receptors. Although their participation in the development of cardiovascular complications is still controversial, some studies have found increased or diminished response to the vasoconstrictive effect of noradrenaline or angiotensin II in a time-dependent manner of diabetes. Thus, the aim of this work was to investigate the possible changes in the expression or localization of α1-AR (α1A and α1D) and angiotensin II receptors (AT1 and AT2) in aorta of rats after 4 weeks of the onset of diabetes. In order to be able to examine the expression of these receptors, immunofluorescence procedure was performed in tunica intima and tunica media of histological sections of aorta. Fluorescence was detected by a confocal microscopy. Our results showed that the receptors are expressed in both tunics, where adrenergic receptors have a higher density in tunica intima and tunica media of SHR compared with WKY; meanwhile, the expression of angiotensin II receptors is not modified in both groups of rats. On the other hand, the results showed that diabetes produced an increase or a decrease in the expression of receptors that is not associated to a specific type of receptor, vascular region, or strain of rat. In conclusion, diabetes and hypertension modify the expression of the receptors in tunica intima and tunica media of aorta in a different way.

  7. Tropisetron ameliorates early diabetic nephropathy in streptozotocin-induced diabetic rats.

    PubMed

    Barzegar-Fallah, Anita; Alimoradi, Houman; Asadi, Firouzeh; Dehpour, Ahmad Reza; Asgari, Mojgan; Shafiei, Massoumeh

    2015-04-01

    It has been well established that oxidative stress and inflammation are involved in the pathogenesis of diabetic nephropathy. It has been shown that tropisetron exerts anti-inflammatory and immunomodulatory properties. The current study was designed to investigate protective effects of tropisetron on early diabetic nephropathy in streptozotocin-induced diabetic rats. Rats were divided into six groups: (i) untreated diabetic (streptozotocin group); (ii) untreated control; (iii) diabetic rats treated with tropisetron (3 mg/kg); (iv) normal rats treated with tropisetron (3 mg/kg); (v) diabetic rats treated with granisetron (3 mg/kg); and (vi) normal rats treated with granisetron (3 mg/kg); rats began receiving treatment at the time of diabetes induction for 2 weeks. At the termination of the experiments, bodyweight, kidney index, urinary albumin excretion, and glomerular filtration rate were measured. The levels of oxidative stress markers and tumour necrosis factor-α were also determined. Streptozotocin-treated animals showed significant loss of bodyweight and renal enlargement and dysfunction. Diabetic rats also exhibited an increase in malondialdehyde along with a significant decrease in glutathione, superoxide dismutase activity, and catalase activity. Furthermore, the diabetic animals demonstrated a significant rise in renal cortical, urinary tumour necrosis factor-α, and urinary albumin excretion. Both granisetron and tropisetron decreased blood glucose in diabetic animals, but this decrease was not significant for granisetron. Treatment with tropisetron, but not granisetron, prevented increases in oxidative stress and tumour necrosis factor-α, decreased urinary cytokine excretion and albuminuria, and improved renal morphological damage. In conclusion, the present study suggests that tropisetron may be a protective agent in early diabetic nephropathy, and its action is mediated, at least in part, by anti-oxidative and anti-inflammatory mechanisms that appear

  8. Dietary zinc modifies diabetic-induced renal pathology in rats.

    PubMed

    Elsaed, Wael M; Mohamed, Hazem Abdelhamid

    2017-11-01

    This study was conducted to investigate how far dietary zinc (Zn) modifies the histomorphological alterations induced by diabetes in rat kidneys. The animals were divided into negative control group (10 rats). Diabetes was induced in thirty animals by streptozotocin. After confirming diabetes, the animals were divided into three groups (n = 10). Group II served as the positive control group (fed on standard diet), group III was fed on Zn deficient diet, and group IV was fed on Zn supplemented diet. Caspase-3 immune staining was used to estimate the caspase activity. Stereological procedures were used to measure the quantity of the immune stain and the surface area of the Bowman's space. The renal cortices of group II rats revealed apparent widening of Bowman's spaces with few apoptotic figures. The filtration barrier showed thickening of the basement membrane. The proximal convoluted tubules showed patchy loss of the apical microvilli with swollen mitochondria. The distal convoluted tubules revealed area of irregular basal enfolding. The picture was aggravated by Zn deficiency in group III besides areas of cortical interstitial fibrosis. The histopathological alterations were minimal in the cortices of group IV. A significant increase of the Bowman's space surface area in group II and IV while decrease in group III compared with group I. The expression of Caspase-3 density was significantly increased in group II and III compared with group I while in group IV was non significant. In conclusion, dietary Zn modulated renal cortical changes caused by diabetes in rats.

  9. The Therapeutic Effect of Zuogui Wan in Gestational Diabetes Mellitus Rats

    PubMed Central

    Feng, Qianjin; Niu, Xin; Liu, Xinshe; Xu, Kaixia; Yang, Xiangzhu; Wang, Huifeng

    2014-01-01

    In this experiment, we established an animal model of gestational diabetes mellitus rats using streptozotocin. Using the rat model of GDM, the pregnant rats in 1-19d were divided into three groups: (1) Zuogui Wan gestational diabetes mellitus group (group I, n = 12), (2) gestational diabetes mellitus rats as the control group (group II, n = 11), and (3) rats of normal pregnancy group (group III, n = 11). Compared with gestational diabetes mellitus rats as the control group, Zuogui Wan can change the indexes of fasting blood glucose, body weight, total cholesterol, insulin, and metabolism cage index significantly in Zuogui Wan gestational diabetes mellitus group. We can conclude that Zuogui Wan has the therapeutic effect on gestational diabetes mellitus. PMID:25136475

  10. Down-Regulation of Renal Gluconeogenesis in Type II Diabetic Rats Following Roux-en-Y Gastric Bypass Surgery: A Potential Mechanism in Hypoglycemic Effect.

    PubMed

    Wen, Yi; Lin, Ning; Yan, Hong-Tao; Luo, Hao; Chen, Guang-Yu; Cui, Jian-Feng; Shi, Li; Chen, Tao; Wang, Tao; Tang, Li-Jun

    2015-01-01

    This study was initiated to evaluate the effects of Roux-en-Y gastric bypass surgery on renal gluconeogenesis in type 2 diabetic rats and its relationship with hormonal parameters. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ; 35 mg/kg) combined with a high-fat diet. They were then randomly divided into three groups: diabetes model group (DM group, n = 8), sham Roux-en-Y gastric bypass group (SRYGB group, n = 8), and Roux-en-Y gastric bypass group (RYGB group, n = 14). Another 8 normal rats comprised the normal control group (NC group, n = 8). Body weight, glucose, serum lipid, insulin, glucagon-like peptide-1 (GLP-1), leptin, and adiponectin were measured pre- and postoperatively. Glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), insulin receptor-α (IR-α), insulin receptor-β (IR-β), and glycogen synthase kinase 3 beta (Gsk3b) were measured in renal cortex by using RT-PCR and Western immune-blot analyses on the 4th week after operation. Following RYGB surgery, surgery-treated rats showed significantly improved oral glucose tolerance, dyslipidemia and insulin resistance as well as increased post-gavage insulin levels and serum circulating levels of GLP-1 and adiponectin. RT-PCR and Western immune-blot analyses showed PEPCK and G6Pase protein and mRNA to be significantly decreased in the renal cortex in the RYGB group (p < 0.05 vs. DM or SRYGB group); in addition, IR-α and Gsk3b phosphorylation levels increased in the RYGB group (p < 0.05 vs. DM or SRYGB group). Down-regulation of renal gluconeogenic enzymes might be a potential mechanism in hypoglycemia. An improved insulin signal pathway in the renal cortex and increased circulating adiponectin concentrations may contribute to the decline of renal gluconeogenesis following RYGB surgery.

  11. Diabetic rat testes: morphological and functional alterations.

    PubMed

    Ricci, G; Catizone, A; Esposito, R; Pisanti, F A; Vietri, M T; Galdieri, M

    2009-12-01

    Reproductive dysfunction is a consequence of diabetes, but the underlying mechanisms are poorly understood. This study investigated the histological and molecular alterations in the testes of rats injected with streptozotocin at prepuperal (SPI rats) and adult age (SAI rats) to understand whether diabetes affects testicular tissue with different severity depending on the age in which this pathological condition starts. The testes of diabetic animals showed frequent abnormal histology, and seminiferous epithelium cytoarchitecture appeared altered as well as the occludin distribution pattern. The early occurrence of diabetes increased the percentage of animals with high number of damaged tubules. The interstitial compartment of the testes was clearly hypertrophic in several portions of the organs both in SPI and SAI rats. Interestingly, fully developed Leydig cells were present in all the treated animals although abnormally distributed. Besides the above-described damages, we found a similar decrease in plasma testosterone levels both in SPI and SAI rats. Oxidative stress (OS) is involved in the pathogenesis of various diabetic complications, and in our experimental models we found that manganese superoxide dismutase was reduced in diabetic animals. We conclude that in STZ-induced diabetes, the altered spermatogenesis, more severe in SPI animals, is possibly due to the effect of OS on Leydig cell function which could cause the testosterone decrease responsible for the alterations found in the seminiferous epithelium of diabetic animals.

  12. Antidepressant effect of taurine in diabetic rats.

    PubMed

    Caletti, Greice; Olguins, Danielly B; Pedrollo, Elis F; Barros, Helena M T; Gomez, Rosane

    2012-10-01

    Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals.

  13. Total parenteral nutrition in diabetic rats

    SciTech Connect

    Norcross, E.D.; Stein, T.P.

    1986-03-01

    Parenteral Nutrition with hypertonic glucose is frequently given to diabetic patients. Large amounts of insulin can be required. The purpose of this investigation was to develop a totally parenterally nourished diabetic rat model. 200 g Female Sprague Dawley rats were made diabetic by i.v. injection of streptozotocin (50 mg/kg). Rats were then allowed to recover for at least 1 week before undergoing surgical insertion of a central venous catheter for parenteral feeding. TPN was begun 3 days after surgery. Prior to this they were allowed unlimited access to food and water. Control (non-streptozotocin treated) rats were run at the same time. Protein turnover was investigated by using /sup 15/N glycine. Preliminary results: diabetic rats given mostly fat as a calorie source survived well in the absence of exogenous insulin whereas those that were given glucose only as their non-protein calorie source showed poor survival even with exogenous insulin. N balance and protein turnover in the lipid treated diabetic rats were comparable to the non-diabetic control rats.

  14. Renal Ischemia/Reperfusion Injury in Diabetic Rats: The Role of Local Ischemic Preconditioning

    PubMed Central

    Ozbilgin, Sule; Ozkardesler, Sevda; Akan, Mert; Boztas, Nilay; Ozbilgin, Mucahit; Ergur, Bekir Ugur; Derici, Serhan; Guneli, Mehmet Ensari; Meseri, Reci

    2016-01-01

    Background. The aim of this study was to evaluate the effects of local ischemic preconditioning using biochemical markers and histopathologically in the diabetic rat renal IR injury model. Methods. DM was induced using streptozotocin. Rats were divided into four groups: Group I, nondiabetic sham group (n = 7), Group II, diabetic sham group (n = 6), Group III, diabetic IR group (diabetic IR group, n = 6), and Group IV, diabetic IR + local ischemic preconditioning group (diabetic IR + LIPC group, n = 6). Ischemic renal injury was induced by clamping the bilateral renal artery for 45 min. 4 h following ischemia, clearance protocols were applied to assess biochemical markers and histopathologically in rat kidneys. Results. The histomorphologic total cell injury scores of the nondiabetic sham group were significantly lower than diabetic sham, diabetic IR, and diabetic IR + LIPC groups. Diabetic IR group scores were not significantly different than the diabetic sham group. But diabetic IR + LIPC group scores were significantly higher than the diabetic sham and diabetic IR groups. Conclusion. Local ischemic preconditioning does not reduce the risk of renal injury induced by ischemia/reperfusion in diabetic rat model. PMID:26925416

  15. Soybeans Ameliolate Diabetic Nephropathy in Rats

    PubMed Central

    Choi, Young Eun; Ahn, Soo Kyung; Lee, Won Taek; Lee, Jong Eun; Park, Seung Hwa; Yoon, Bang Bu

    2010-01-01

    Diabetic nephropathy is one of the most frequent and serious complications of diabetes mellitus. Soybeans have been shown to reduce urinary albumin excretion and total cholesterol in non-diabetic patients with nephrotic syndrome. However, reports focusing specifically on diabetic nephropathy are scarce and the available results are inconsistent. It was reported that soybean consumption reduced urinary protein excretion in type 1 diabetic patients with diabetic nephropathy, whereas it was found to elicit an increase in urinary protein excretion when soybeans were consumed by type 2 diabetic patients. This study aims to investigate the effects of soybean in diabetic nephropathy, particularly the effects of consuming soybeans on the histopathology of diabetic nephropathy, using aquaporin (AQP) and osteopontin (OPN) expression as diagnostic markers. Male Sprague-Dawley rats were assigned to one of three groups: control, diabetic with red chow diet and diabetic with soybean diet. For histological examination, the expression of OPN and AQP, renal function and hemoglobin A1c were evaluated at the end of the study. Improvements in glomerular and tubulointerstitial lesions were demonstrated in the diabetic rat group given a soybean diet. OPN and AQP expression were suppressed in the kidney specimens of diabetic rats with the soybean diet. In conclusion, soybeans may prevent the weight loss and morphological disruption of the kidney associated with diabetes mellitus. Soybeans also may improve glycemic control. It seems likely that long-term control of blood glucose levels using a soybean diet could prevent the progression of diabetes mellitus, and therefore, nephropathy could be prevented. PMID:18955330

  16. Study of Calcium Dobesilate in Diabetic Rats.

    PubMed

    Tejerina; Ruiz; Sanz; Ganado

    1999-01-01

    According to the World Health Organization (WHO) 74% of diabetic patients die of vascular complications. Previous reports have shown that endothelium-dependent relaxation of diabetic vasculature is more sensitive to free radical-induced injury. Calcium dobesilate (DOBE) has been successfully used in the treatment of diabetic retinopathy. The aims of this study were to investigate the in vivo and ex vitro effects of DOBE on both contractile and relaxing responses in isolated diabetic rat aorta. Four groups of rats were used: Wistar rats (Group 0); spontaneously diabetic rats (BB/wor rats) (Group 1); BB/wor rats treated with DOBE 50 mg/kg/day (Group 2); and BB/wor rats treated with 500 mg/kg/day (Group 3). At 180 days after the development of diabetes, the animals were killed and the thoracic aorta were isolated, cleaned off, and mounted in an organ chamber. Two groups of experiments were carried out. In the first group (in vitro), incubation with DOBE 10(-4) in aortic rings isolated from BB/wor rats decreased the contraction induced by noradrenaline (NA) 10(-6) M (1.21 +/- 0.11 g vs 0.67 +/- 0.01 g P < 0.01, n = 8 in diabetic rings with or without the presence of DOBE 10(-4) M, respectively), and this decrease was prevented by propranolol 10(-6) M (1.20 +/- 0.6 g). DOBE 10(-5) and 10(-4) M increased the endothelium-dependent relaxation induced by ACh in BB/wor rats [the maximal relaxation with ACh 10(-5) M was 50.0 +/- 5.1 vs 72.0 +/- 11.0 (p < 0.05, n = 8) and 69.0 +/- 7.8 (p < 0.05, n = 8) in BB/wor rats and after the incubation with DOBE 10(-5) and 10(-4) M, respectively], however, incubation with DOBE did not modify the endothelium-independent relaxation in these rats. In the second part of the study (ex vitro), we found an increase in the endothelium-dependent relaxation in arteries from diabetic rats treated with DOBE (Groups 2) compared with Group 1 (BB/wor rats) although we did not find any improvement in the endothelium-independent relaxation. Thus, in

  17. Anti diabetic effect of cherries in alloxan induced diabetic rats.

    PubMed

    Lachin, Tahsini; Reza, Heydari

    2012-01-01

    Diabetes mellitus (DM) is a metabolic disorder in the endocrine system resulting from a defect in insulin secretion, insulin action or both of them. Adverse side effects of chemical drugs for treatment of diabetes persuaded the using of medical plants. Cherry as a traditionally used plant for treatment of diabetes, is packed with powerful plant pigments called anthocyanins. They give cherries their dark red color and are one of the richest antioxidant sources which lower the blood sugar and bear other beneficial health effects. The purpose of this study is to evaluate the effect of ethanolic extract of cherry fruit on alloxan induced diabetic rats. In this study 36 Male Wistar rats, body weight of 150-200gr were divided into 6 groups. Diabetes was induced by intra peritoneal injection of 120 mg/kg Alloxan. The duration of the cherries treatment was 30 days in which single dose of extracts (200mg/kg) were oral administered to diabetic rats. Blood glucose levels were estimated with glucometer before treatment, 2h and 1- 4 weeks after administration of extracts. Treatment with extracts of the cherries resulted in a significant reduction in blood glucose and urinary microalbumin and an increase in the creatinine secretion level in urea. Extract of this plant is useful in controlling the blood glucose level. Cherries appear to aid in diabetes control and diminution of the complications of the disease. Some relevant patents are also outlined in this article.

  18. Testicular lesions of streptozotocin diabetic rats.

    PubMed

    Oksanen, A

    1975-01-01

    Diabetes was induced in adult male albino rats by a single intravenous injection of streptozotocin (75 mg/kg body weight). The diabetes was allowed to stabilize for at least 15 days, whereafter the testicular and seminal vesicle histology was studied at various time intervals. Reduction in testis weights and tubule diameters was significant after 2 weeks of diabetes. The changes in seminiferous tubules ranged from premature sloughing of epithelium to total cessation of spermatogenesis. The testicular histology of diabetic animals frequently greatly simulated the situation described following hypophysectomy. By subjective visual assessment the number of Leydig cells was found to be normal or reduced in all of the diabetic animals. Diabetes was also demonstrated to induce seminal vesicle atrophy, which did not show any correlation with the degree of testicular lesions. The possible etiology of testicular damage in diabetic animals is discussed.

  19. FREE FATTY ACIDS PROFILING IN RESPONSE TO CARNITINE SYNERGIZE WITH LUTEIN IN DIABETIC RATS.

    PubMed

    Al-Malki, Abdulrahman L; Moselhy, Said S

    2016-01-01

    The objective of this study was to investigate the fatty acids profiling in diabetic rats induced by sterptozocine (STZ) and their response to administration of lutein and carnitine. Ninety male albino rats were divided into 6 groups as follows: Normal control. The remaining rats were injected i.p a single dose of STZ (65 mg /kg bw) for induction of diabetes. Diabetic rats were grouped as: GP II: (Untreated): GP III: Rats were given orally with L-lutein (100 mg/kg bw).GP IV: Rats were given carnitine (30 μg/kg) i.p. GP V: Rats were given carnitine and lutein GP VI were given metformin (100mg/kg bw/d) for 6 weeks. Treatment of diabetic rats with lutein, L-carnitine, combined decreased the levels of glucose, HA1C compared with untreated diabetic (p<0.001). Administration of L-lutein, carnitine, combined to normal rats significantly decreased the levels of myristic, palmitice, palmitoleic, stearic, linoleic, α-linolenic, arachidic and eicosadienoic when compared with control normal rats (p<0.001). Abnormalities of fatty acids composition was observed in diabetic rats. Combination treatment with lutein and carnitine could ameliorate deleterious effect induced by STZ and attenuate the changed fatty acid composition.

  20. Acute and subchronic antihyperglycemic activities of Bowdichia virgilioides roots in non-diabetic and diabetic rats

    PubMed Central

    Silva, Ana Carolina Mazei; dos Santos, Maísa Pavani; de França, Suélem Aparecida; da Silva, Virginia Claudia; da Silva, Luiz Everson; de Figueiredo, Uir Santana; Dall’Oglio, Evandro Luiz; Júnior, Paulo Teixeira de Sousa; Lopes, Carbene França; Baviera, Amanda Martins; Kawashita, Nair Honda

    2015-01-01

    Aim: The present study was undertaken to evaluate the acute and subchronic antihyperglycemic effects of methanolic extract of Bowdichia virgilioides root bark of B. virgilioides in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: The extract (100, 250 or 500 mg/kg) was orally administered to male Wistar diabetic (STZ, 42 mg/kg i.v.) and non-diabetic rats into two main protocols: (i) subchronic experiments, where animals were treated for 21 days with B. virgilioides extract and the following parameters were evaluated: Body weight, fluid and food intake (determined daily), urinary glucose and urea (every 3 days) and glycemia (every 5 days). At the end of the experimental period, skeletal muscles (extensor digitorum longus [EDL] and soleus), retroperitoneal and epididymal white adipose tissues were collected and weighed; liver samples were used for the determination of the lipid and glycogen contents; (ii) acute experiments, which evaluated the alterations on fasting and post-prandial glycemia and on glucose tolerance using the oral glucose tolerance test (OGTT). Results: In subchronic experiments, the treatment with B. virgilioides extract did not change any parameter evaluated in diabetic and non-diabetic animals. On fasting and post-prandial glycemia, the extract treatment did not promote changes in the glycemia values in diabetic or non-diabetic animals. In OGTT, the treatment with 500 mg/kg B. virgilioides extract reduced the hyperglycemia peak after a glucose overload, when compared with non-treated diabetic animals, resulting in a lower area under curve. Conclusion: The results of our work indicate that B. virgilioides root extract promotes an acute antihyperglycemic effect in STZ-diabetic rats; this effect probably occurs through an inhibition of the intestinal glucose absorption. The continuity of the research is necessary to elucidate these possibilities. PMID:26401386

  1. Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats.

    PubMed

    Shinde, Urmila A; Goyal, R K

    2003-01-01

    Earlier studies from our laboratory have indicated insulin sensitizing action of chromium picolinate as the mechanism of its anti-diabetic activity in experimental models of type I and type II diabetes. In the present investigation, we have evaluated the effects of chronic administration of chromium picolinate on the functional and histological alterations of streptozotocin (STZ)-induced diabetes in rats. Type I diabetes was induced by intravenous injection of STZ (40 mg/kg) in adult rats, whereas, type II diabetes was induced by intraperitoneal injection of STZ (90 mg/kg) in 2-day old rat pups which in adulthood develop abnormalities resembling type II diabetes. Chromium picolinate was administered at 8 microg/ml in drinking water for 6 weeks and was found to improve glucose tolerance and increase insulin sensitivity of STZ-diabetic rats. This treatment decrease elevated serum creatinine and urea levels as well as elevated serum levels of hepatic enzymes of both groups of diabetic rats. Histopathological studies of kidney and liver show decrease in the intensity and incidence of vacuolations, cellular infiltration and hypertrophy of STZ and nSTZ (neonatal STZ) diabetic rats. Chronic treatment with chromium picolinate however, did not alter the normal function or morphology of control rats. Chronic chromium picolinate at the therapeutic doses that improved glucose tolerance, was observed to have no hepatotoxic or nephrotoxic potential. It was rather found to improve renal and hepatic function and to reduce abnormalities associated with STZ-diabetes. Chromium picolinate could play an important role in the long term management of diabetes mellitus.

  2. Antihyperlipidemic effect of D-pinitol on streptozotocin-induced diabetic Wistar rats.

    PubMed

    Geethan, P K M Anu; Prince, P Stanely Mainzen

    2008-01-01

    D-pinitol (3-O-methyl-chiroinositol), an active principle of the traditional antidiabetic plant, Bougainvillea spectabilis, is claimed to exert insulin-like effects. This study was undertaken to evaluate the effect of D-pinitol on lipids and lipoproteins in streptozotocin (STZ)-induced diabetic Wistar rats. Rats were made type II diabetic by single intraperitoneal injection of STZ at a dose of 40 mg/kg body weight. STZ-induced diabetic rats showed significant (p < 0.05) increase in the levels of blood glucose and total cholesterol, triglycerides, free fatty acids, and phospholipids in serum, liver, kidney, heart, and brain. The levels of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) cholesterol were significantly increased, and the level of high-density lipoprotein (HDL) cholesterol was significantly decreased in diabetic rats Oral administration of D-pinitol to STZ-induced diabetic rats showed significant (p < 0.05) decrease in the levels of blood glucose and total cholesterol, triglycerides, free fatty acids, and phospholipids in serum, liver, kidney, heart, and brain. The D-pinitol also lowered significantly (p < 0.05) LDL and VLDL cholesterol levels and increased significantly (p < 0.05) HDL cholesterol levels in the serum of diabetic rats. Thus, the present study clearly showed the antihyperlipidemic effect of D-pinitol in STZ-induced type II diabetic rats.

  3. Pulpal and periodontal diseases increase triglyceride levels in diabetic rats.

    PubMed

    Cintra, Luciano Tavares Angelo; da Silva Facundo, Aguinaldo Cândido; Azuma, Mariane Maffei; Sumida, Dóris Hissako; Astolphi, Rafael Dias; Bomfim, Suely Regina Mogami; Narciso, Luís Gustavo; Gomes-Filho, João Eduardo

    2013-07-01

    The aim of this study was to evaluate triglyceride and cholesterol levels in diabetic rats and their relationship with pulpal and periodontal diseases. Eighty male rats (Rattus norvegicus albinus, Wistar) were divided into the following eight groups comprising ten animals each: normal rats (G1), rats with pulpal diseases (G2), rats with periodontal diseases (G3), rats with both pulpal and periodontal diseases (G4), diabetic rats (G5), diabetic rats with pulpal diseases (G6), diabetic rats with periodontal diseases (G7), and diabetic rats with both periodontal and pulpal diseases (G8). Diabetes was induced by injecting streptozotocin, periapical lesions were induced by exposing pulpal tissue to the oral environment, and periodontal diseases were induced by periodontal ligature. The animals were killed after 30 days, and lipid profile was enzymatically measured using Trinder's method. The total assessed values were statistically analyzed by analysis of variance and Tukey test (p < 0.05). The triglyceride levels of diabetic rats with periodontal disease and of diabetic rats with both periodontal and pulpal diseases were significantly higher than those of normal rats and nondiabetic group rats, respectively. The differences in the cholesterol levels among the groups were not significant. We found that the association of pulpal and periodontal diseases with diabetes increased triglyceride levels in rats. Changes in lipid profile may be related to the presence of oral infections and diabetes.

  4. Hypoglycemic Activity of Fumaria parviflora in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Fathiazad, Fatemeh; Hamedeyazdan, Sanaz; Khosropanah, Mohamad Karim; Khaki, Arash

    2013-01-01

    Purpose: Fumaria parviflora Lam (Fumariaceae) has been used in traditional medicine in the treatment of several diseases such as diabetes. The present work was designed to evaluate the hypoglycaemic effects of methanolic extract (ME) of F. parviflora in normal and streptozotocin-induced diabetic rats. Methods: The rats used were allocated in six (I, II, III, IV, V and VI) experimental groups (n=5). Group I rats served as ‘normal control’ animals received distilled water and group II rats served as ‘diabetic control’ animals. Diabetes mellitus was induced in groups II, V and VI rats by intraperitoneal single injection of streptozotocin (STZ, 55 mg kg-1). Group V and VI rats were addi-tionally treated with ME (150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively) 24 hour post STZ injection, for seven consecutive days. Groups III and IV rats received only ME 150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively for seven days. The levels of blood glucose were determined using a Glucometer. Results: Administra-tion of F. parviflora extract showed a potent glucose lowering effect only on streptozo-tocin (STZ) induced diabetic rats below 100 mg/dl (P<0.001). However, no significant differences in the blood glucose levels were recorded between diabetic rats received 125 or 250 mg/kg of plant extracts. Conclusion: The findings of the study indicated that F. parviflora has significant hypoglycemic effect on STZ-induced diabetic rats with no effects on blood glucose levels of normal rats. PMID:24312837

  5. Comparison of the effects of levocetirizine and losartan on diabetic nephropathy and vascular dysfunction in streptozotocin-induced diabetic rats.

    PubMed

    Anbar, Hanan S; Shehatou, George S G; Suddek, Ghada M; Gameil, Nariman M

    2016-06-05

    This work was designed to investigate the effects of levocetirizine, a histamine H1 receptor antagonist, on diabetes-induced nephropathy and vascular disorder, in comparison to an angiotensin II receptor antagonist, losartan. Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of streptozotocin (50mg/kg). Diabetic rats were divided into three groups; diabetic, diabetic-levocetirizine (0.5mg/kg/day) and diabetic-losartan (25mg/kg/day). Treatments were started two weeks following diabetes induction and continued for additional eight weeks. At the end of the experiment, urine was collected and serum was separated for biochemical measurements. Tissue homogenates of kidney and aorta were prepared for measuring oxidative stress, nitric oxide (NO), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Moreover, histological analyses were conducted and aortic vascular reactivity was investigated. Levocetirizine improved renal function in diabetic rats (evidenced by mitigation of diabetes-induced changes in kidney to body weight ratio, serum albumin, urinary proteins and creatinine clearance). Moreover, levocetirizine attenuated the elevated renal levels of TNF-α and TGF-β1, ameliorated renal oxidative stress and restored NO bioavailability in diabetic kidney. These effects were comparable to or surpassed those produced by losartan. Moreover, levocetirizine, similar to losartan, reduced the enhanced responsiveness of diabetic aorta to phenylephrine. Histological evaluation of renal and aortic tissues further confirmed the beneficial effects of levocetirizine on diabetic nephropathy and revealed a greater attenuation of diabetes-induced vascular hypertrophy by levocetirizine than by losartan. In conclusion, levocetirizine may offer comparable renoprotective effect to, and possibly superior vasculoprotective effects than, losartan in streptozotocin-diabetic rats.

  6. Expression of oxytocin receptor in diabetic rat penis.

    PubMed

    Li, M; Wang, T; Guo, S; Rao, K; Liu, J; Ye, Z

    2012-05-01

    Oxytocin receptor (OTR) expressed in the rat penis and mediated the contractility of the corpus cavernosum smooth muscle both in vitro and in vivo, and OTR could maintain penile detumescence; however, the expression of OTR in diabetic rat penis remains unknown. In the present study, we investigated the expression of OTR in diabetic rat penis. The experimental rats were randomly divided into control group and STZ-diabetic rats group. The expressions of mRNA and protein were examined by real-time quantitative PCR, Western blotting and immunohistochemistry respectively. Erectile function was evaluated by measuring intracavernous pressure following electrostimulation of the cavernous nerves. mRNA and protein expression of OTR significantly increased in diabetic rats group compared with the control group. Erectile function of diabetic rats group significantly decreased compared with the control group. Our data showed that the expression of OTR significantly increased in diabetic rats group and OTR may involve in the development of diabetic erectile dysfunction.

  7. [Berberine inhibits cardiac fibrosis of diabetic rats].

    PubMed

    Lu, Kun; Shen, Yongjie; He, Jinfeng; Liu, Guoling; Song, Wei

    2016-10-01

    Objective To explore the effect of berberine on cardiac fibrosis of diabetic rats by observing the expressions of serum transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) , collagen type 1 (Col1) and collagen type 3 (Col3) in myocardial tissues of diabetic rats after berberine treatment. Methods The diabetic model was induced by intraperitoneal injection of streptococci (STZ). Forty-three diabetic rats were randomly divided into diabetic model group (n=9), berberine treated groups of different doses [50, 100, 150 mg/(kg.d), gavage administration for 12 weeks; n=9, 9, 8 respectively], and metformin group as positive control (n=8); other 8 normal rats served as a negative control group. After the last administration, fasting blood glucose, left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP) were measured; rats' heart were taken to calculate the heart mass index (HMI); ELISA was used to detect the serum levels of TGF-β1 and CTGF; collagenous fibers in cardiac tissues were tested by Masson staining; collagen volume fraction (CVF) was measured by image analysis; Col1 and Col3 in cardiac tissues were determined by Western blotting. Results Compared with the normal control group, the fasting blood glucose, LVSP, LVEDP absolute value, HMI, the degree of cardiac fibrosis, the expressions of TGF-β1, CTGF, Col1 and Col3 significantly increased in the model group. All indexes mentioned above were reduced obviously in berberine treated groups of 100 and 150 mg/(kg.d). Conclusion Berberine improves cardiac fibrosis in diabetic rats through down-regulating the expressions of TGF-β1 and CTGF and reducing the synthesis and deposition of Col1 and Col3.

  8. Effect of alpha lipoic acid on oxidative stress and vascular wall of diabetic rats.

    PubMed

    Balkis Budin, Siti; Othman, Faizah; Louis, S R; Abu Bakar, M; Radzi, M; Osman, K; Das, S; Mohamed, J

    2009-01-01

    PREMISES AND OBJECTIVES: Antioxidant plays an important role in preventing the progression of diabetes mellitus (DM) complications. The aim of the present study was to investigate the effect of alpha lipoic acid (ALA) supplementation on plasma lipid, oxidative stress and vascular changes in diabetic rats. Diabetes was induced by a single intravenous injection of streptozotocin (STZ) (50 mg/kg). The diabetic rats were divided into two groups: (i) supplemented group with ALA (100 mg/kg/day) and (ii) non-supplemented group without ALA. Non-diabetic rats (NDM) formed the control group, which received saline injection. Following eight weeks of supplementation, fasting blood glucose (FBG) and glycosylated hemoglobin (HBA1c) in ALA-supplemented rats was found to be significantly lower than the non-supplemented group. ALA-supplementation also improved dyslipidemia that occurred in diabetic rats. ALA-supplementation also significantly increased plasma superoxide dismutase (SOD) activity and vitamin C level as compared to the No Suppl group. The increase in plasma and aorta malondealdehyde + 4-hydroxynonenal (MDA + 4-HNE) levels were also inhibited and the levels of oxidative DNA damage of peripheral lymphocytes were significantly reduced. Electron microscopic examination of thoracic aorta revealed that normal tissue organization was disrupted in STZ-diabetic rats with ALA-supplementation reducing the changes in the vascular morphology. It is concluded that ALA has the potential in preventing the alteration of vascular morphology in diabetic rats probably through the improvement of glycemic status and dyslipidemia as well as its antioxidant activities.

  9. Ozone partially prevents diabetic neuropathy in rats.

    PubMed

    Erken, H A; Genç, O; Erken, G; Ayada, C; Gündoğdu, G; Doğan, H

    2015-02-01

    Neuropathy is one of the most common complications of diabetes mellitus. Although the beneficial effects of good blood glucose control on diabetic neuropathy are known, this control cannot completely prevent the occurrence and progression of diabetic neuropathy. The aim of this study was to investigate whether ozone prevents diabetic neuropathy. 36 adult female Sprague-Dawley rats were randomly divided into 6 groups (n=6): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone- and insulin-treated diabetic (DOI). Diabetes was induced by a single injection of streptozotocin (60 mg/kg, intraperitoneal [i.p.]), after which insulin was administered (3 IU, i.p.) to the DI and DOI groups for 28 days, and 1.1 mg/kg (50 µg/ml) ozone was given to the O, DO, and DOI groups for 15 days. 4 weeks after the induction of diabetes, the nerve conduction velocity (NCV), amplitude of the compound action potential (CAP), total oxidant status (TOS), and total antioxidant status (TAS) were measured, and the oxidative stress index (OSI) was calculated. The NCV, amplitude of CAP, and TAS of the DI and DOI groups were higher than those of the D group; the amplitudes of CAP and TAS of the DO group were higher than those of the D group; and the TOS and OSI of the DO, DI, and DOI groups were lower than those of the D group. These findings indicate that ozone partially prevents diabetic neuropathy in rats. It appears that the preventive effects of ozone are mediated through oxidant/antioxidant mechanisms.

  10. Wound healing activity of Malva sylvestris and Punica granatum in alloxan-induced diabetic rats.

    PubMed

    Pirbalouti, Abdollah Ghasemi; Azizi, Shahrzad; Koohpayeh, Abed; Hamedi, Behzad

    2010-01-01

    The flowers of Malva sylvestris Linn. (Malvaceae) and Punica granatum Linn. (Punicaceae) are important medicinal plants in Iranian traditional medicine (Unani) whose have been used as remedy against edema, bum, wound and for their carminative, antimicrobial and anti-inflammatory activities. The diethyl ether extract of M. sylvestris and P. granatum flowers were used to evaluate the wound healing activity at 200 mg/kg/day dose in alloxan-induced diabetic rats. Wounds were induced in Wister rats divided into six groups as following; Group I, normal rats were treated with simple ointment base. Group II, diabetic rats were treated with simple ointment base (control). Groups III and IV, diabetic rats were treated with simple ointment base containing of extracts (diabetic animals), Groups V, diabetic rats were treated with simple ointment base containing of mixed extracts (1:1), Group VI, diabetic rats received the standard drug (nitrofurazone). The efficacy of treatment was evaluated based on wound area relative and histopathological characteristics. The extract-treated diabetic animals showed significant reduction in the wound area when compared with control. Also, histological studies of the tissue obtained on days 9th and 18th from the extract-treated by extract of M. sylvestris showed increased well organized bands of collagen, more fibroblasts and few inflammatory cells. These findings demonstrate that extract of M. sylvestis effectively stimulates wound contraction as compared to control group and other groups. M. sylvestris accelerated wound healing in rats and thus supports its traditional use.

  11. Photobiomodulation improves cutaneous wound healing in an animal model of type II diabetes.

    PubMed

    Byrnes, Kimberly R; Barna, Lauren; Chenault, V Michelle; Waynant, Ronald W; Ilev, Ilko K; Longo, Leonardo; Miracco, Clelia; Johnson, Bryan; Anders, Juanita J

    2004-08-01

    We investigated the effects of photobiomodulation (PBM) on cutaneous wound healing in an animal model of type II diabetes, Psammomys obesus (Sand Rats). 632-nm light has been established as the most effective wavelength for treatment of cutaneous wounds; however, the inconsistent efficacy of PBM may be due to inadequate treatment parameter selection. Using 632-nm light, an initial series of experiments were done to establish optimal treatment parameters for this model. Following creation of bilateral full-thickness skin wounds, non-diabetic Sand Rats were treated with PBM of differing dosages. Wound healing was assessed according to wound closure and histological characteristics of healing. Optimal treatment parameters were then used to treat type II diabetic Sand Rats while a diabetic control group received no irradiation. In order to elucidate the mechanism behind an improvement in wound healing, expression of basic fibroblast growth factor (bFGF) was assessed. Significant improvement in wound healing histology and wound closure were found following treatment with 4 J/cm(2) (16 mW, 250-sec treatments for 4 consecutive days; p < 0.05). The 4 J/cm(2) dosage significantly improved histology and closure of wounds in the diabetic group in comparison to the non-irradiated diabetic group. Quantitative analysis of bFGF expression at 36 h post-injury revealed a threefold increase in the diabetic and non-diabetic Sand Rats after PBM. The results demonstrate that PBM at an energy density of 4 J/cm(2) is effective in improving the healing of cutaneous wounds in an animal model of type II diabetes, suggesting that PBM (632 nm, 4 J/cm(2)) would be effective in treating chronic cutaneous wounds in diabetic patients.

  12. Antioxidant effects of a grape seed extract in a rat model of diabetes mellitus.

    PubMed

    Chis, Irina C; Ungureanu, Marius I; Marton, Adriana; Simedrea, Ramona; Muresan, Adriana; Postescu, Ion-Dan; Decea, Nicoleta

    2009-07-01

    In the present study we investigated the anti-hyperglycaemic and antioxidant effect of grape seed extract, a polyphenolic flavonoid, in normal and streptozotocin-induced diabetic Wistar rats. Adult male Wistar rats were divided into three groups: Group I: non-diabetic control; Group II: diabetic control; Group III: diabetic rats treated with grape seed extract, administered via an intragastric tube (0.6 ml/rat), at a dose of 100 mg/kg for 20 consecutive days after the induction of diabetes mellitus. Diabetes was induced by an i.p. injection with streptozotocin for groups II and III. TheTBARS, carbonylated proteins, were measured in the plasma and in the supernatant of liver homogenisates, and superoxide dismutase and catalase were measured in the haemolysates of RBCs and supernatant of liver homogenisates. The results showed that oral administration of grape seed extract (100 mg/kg/day) reduced the levels of lipid peroxides and carbonylated proteins and improved the antioxidant activity in plasma and hepatic tissue in rats treated with grape seed natural extract as compared with the diabetic control rats. These results suggested that the grape seed extract enhanced the antioxidant defence against reactive oxygen species produced under hyperglycaemic conditions, hence protecting the liver cells.

  13. Obestatin and insulin in pancreas of newborn diabetic rats treated with exogenous ghrelin.

    PubMed

    Turk, Neslihan; Dağistanli, Fatma Kaya; Sacan, Ozlem; Yanardag, Refiye; Bolkent, Sema

    2012-07-01

    The aim of the study was to evaluate the effect of ghrelin treatment on obestatin, insulin gene expression and biochemical parameters in the pancreas of newborn-streptozocin (STZ) diabetic rats. Rats were divided into 4 groups. Group I: control rats treated with physiological saline; group II: control rats treated with 100 μg/kg/day ghrelin; group III: two days after birth rats that received 100mg/kg STZ injected as a single dose to induce neonatal diabetes; group IV: neonatal-STZ-diabetic rats treated with ghrelin for four weeks. Sections of the pancreas were examined with immunohistochemistry for the expression of obestatin and insulin and in situ hybridization for the expression of insulin mRNA. The blood glucose levels were measured. Tissue homogenates were used for protein, glutathione, lipid peroxidation and non-enzymatic glycosylation levels and antioxidant enzyme analysis. There was a significant difference in blood glucose levels in newborn-STZ-diabetic rats compared to ghrelin treated diabetic rats at weeks 1, 2 and 4. In group IV, pancreatic non-enzymatic glycosylation and lipid peroxidation levels were decreased, however, glutathione levels and enzymatic activities were increased. Insulin peptide and mRNA (+) signals in islets of Langerhans and obestatin immunopositive cell numbers showed an increase in group IV compared to group III. These results suggest that administration of ghrelin to newborn rats may prevent effects of diabetes.

  14. Relationship between Immunological Abnormalities in Rat Models of Diabetes Mellitus and the Amplification Circuits for Diabetes.

    PubMed

    Takeda, Yuji; Shimomura, Tomoko; Asao, Hironobu; Wakabayashi, Ichiro

    2017-01-01

    A better understanding of pathogenic mechanisms is required in order to treat diseases. However, the mechanisms of diabetes mellitus and diabetic complications are extremely complex. Immune reactions are involved in the pathogenesis of diabetes and its complications, while diabetes influences immune reactions. Furthermore, both diabetes and immune reactions are influenced by genetic and environmental factors. To address these issues, animal models are useful tools. So far, various animal models of diabetes have been developed in rats, which have advantages over mice models in terms of the larger volume of tissue samples and the variety of type 2 diabetes models. In this review, we introduce rat models of diabetes and summarize the immune reactions in diabetic rat models. Finally, we speculate on the relationship between immune reactions and diabetic episodes. For example, diabetes-prone Biobreeding rats, type 1 diabetes model rats, exhibit increased autoreactive cellular and inflammatory immune reactions, while Goto-Kakizaki rats, type 2 diabetes model rats, exhibit increased Th2 reactions and attenuation of phagocytic activity. Investigation of immunological abnormalities in various diabetic rat models is useful for elucidating complicated mechanisms in the pathophysiology of diabetes. Studying immunological alterations, such as predominance of Th1/17 or Th2 cells, humoral immunity, and innate immune reactions, may improve understanding the structure of amplification circuits for diabetes in future studies.

  15. Relationship between Immunological Abnormalities in Rat Models of Diabetes Mellitus and the Amplification Circuits for Diabetes

    PubMed Central

    Shimomura, Tomoko; Asao, Hironobu; Wakabayashi, Ichiro

    2017-01-01

    A better understanding of pathogenic mechanisms is required in order to treat diseases. However, the mechanisms of diabetes mellitus and diabetic complications are extremely complex. Immune reactions are involved in the pathogenesis of diabetes and its complications, while diabetes influences immune reactions. Furthermore, both diabetes and immune reactions are influenced by genetic and environmental factors. To address these issues, animal models are useful tools. So far, various animal models of diabetes have been developed in rats, which have advantages over mice models in terms of the larger volume of tissue samples and the variety of type 2 diabetes models. In this review, we introduce rat models of diabetes and summarize the immune reactions in diabetic rat models. Finally, we speculate on the relationship between immune reactions and diabetic episodes. For example, diabetes-prone Biobreeding rats, type 1 diabetes model rats, exhibit increased autoreactive cellular and inflammatory immune reactions, while Goto-Kakizaki rats, type 2 diabetes model rats, exhibit increased Th2 reactions and attenuation of phagocytic activity. Investigation of immunological abnormalities in various diabetic rat models is useful for elucidating complicated mechanisms in the pathophysiology of diabetes. Studying immunological alterations, such as predominance of Th1/17 or Th2 cells, humoral immunity, and innate immune reactions, may improve understanding the structure of amplification circuits for diabetes in future studies. PMID:28299342

  16. Genistein Treatment Confers Protection against Gliopathy and Vasculopathy of the Diabetic Retina in Rats.

    PubMed

    Elgayar, Sanaa A M; Eltony, Sohair A; Sayed, Abdelrahman A; Abdel-Rouf, Maha M

    2015-01-01

    Retinopathy remains an important complication of diabetes. This work was carried out to evaluate the protective effects of genistein from diabetic retinopathy in rat. Fifteen adult male albino rats were divided into two groups; Group I: control (n = 5) and Group II: streptozotocin induced diabetic group (n = 10), which is equally divided into two subgroups; IIa (diabetic vehicle control) and IIb (diabetic genistein-treated). Specimens were taken from the retina 12 weeks post induction, processed and examined using light, immunohistochemical, ultrastructural techniques. Blood samples were assayed for the levels of glucose. In comparison with the diabetic non-treated group, the histological changes in macro and microglial glial cells reactivity and retinal blood capillaries were improved in genistein-treated groups. In addition, GFAP and iNOS expressions in the retina and the blood glucose level were reduced. Genistein ameliorates the histological changes of diabetic retinopathy reaching healing features, which resemble that of a normal retina.

  17. Heme Oxygenase-1 Promotes Delayed Wound Healing in Diabetic Rats

    PubMed Central

    Chen, Qing-Ying; Wang, Guo-Guang; Li, Wei; Jiang, Yu-Xin; Lu, Xiao-Hua; Zhou, Ping-Ping

    2016-01-01

    Diabetic ulcers are one of the most serious and costly chronic complications for diabetic patients. Hyperglycemia-induced oxidative stress may play an important role in diabetes and its complications. The aim of the study was to explore the effect of heme oxygenase-1 on wound closure in diabetic rats. Diabetic wound model was prepared by making an incision with full thickness in STZ-induced diabetic rats. Wounds from diabetic rats were treated with 10% hemin ointment for 21 days. Increase of HO-1 protein expression enhanced anti-inflammation and antioxidant in diabetic rats. Furthermore, HO-1 increased the levels of VEGF and ICAM-1 and expressions of CBS and CSE protein. In summary, HO-1 promoted the wound closure by augmenting anti-inflammation, antioxidant, and angiogenesis in diabetic rats. PMID:26798657

  18. Does radio frequency radiation induce micronuclei frequency in exfoliated bladder cells of diabetic rats?

    PubMed

    Gurbuz, N; Sirav, B; Kuzay, D; Ozer, C; Seyhan, N

    2015-07-01

    For many years there has been a discussion among both experts and the general public regarding the effects of radio frequency (RF) radiation on the human organism. The purpose of the present study was to evaluate the relationship of micronucleui (MN) frequency and RF radiation in exfoliated bladder cells of non-diabetic and diabetic rats. Three groups were used in the experiment: Group I (n=6): diabetic group without RF exposure; Group II (n=6): diabetic group exposed 2100 MHz RF radiation and Group III (n=6): control animals (non-diabetic group, no RF exposure). RF exposure in the experiment resulted in a whole body average SAR of 0.24 W/kg with an ERMS field of 17.5 V/m in non-thermal levels. Results showed that there was no statistically important differences between non-RF exposed diabetes group and control group; Group I and Group III (p>0.05). There was no statistically important differences between diabetes group and diabetes+RF exposed group (Group I and Group II) (p>0.05). RF exposure did not result in increased MN frequencies in exfoliated bladder cells of diabetic rats with respect to control animals (Group II and Group III), either and this result found no statistically important (p>0.05). This study suggested no possible genotoxic effects of RF radiation among human beings especially with chronic disorders, such as diabetes.

  19. Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats

    PubMed Central

    Bujak-Giżycka, B.; Jawień, J.; Olszanecki, R.; Madej, J.; Rutowski, J.; Korbut, R.

    2016-01-01

    Purpose. Products of angiotensin (ANG) I metabolism may predispose to vascular complications of diabetes mellitus. Methods. Diabetes was induced with streptozotocin (75 mg/kg i.p.). Rat aorta fragments, isolated 4 weeks later, were pretreated with perindoprilat (3 μM), thiorphan (3 μM), or vehicle and incubated for 15 minutes with ANG I (1 μM). Products of ANG I metabolism through classical (ANG II, ANG III, and ANG IV) and alternative (ANG (1–9), ANG (1–7), and ANG (1–5)) pathways were measured in the buffer, using liquid chromatography-mass spectrometry. Results. Incubation with ANG I resulted in higher concentration of ANG II (P = 0.02, vehicle pretreatment) and lower of ANG (1–9) (P = 0.048, perindoprilat pretreatment) in diabetes. Preference for the classical pathway is suggested by higher ANG III/ANG (1–7) ratios in vehicle (P = 0.03), perindoprilat (P = 0.02), and thiorphan pretreated (P = 0.02) diabetic rat. Within the classical pathway, ratios of ANG IV/ANG II (P = 0.01) and of ANG IV/ANG III (P = 0.049), but not of ANG III/ANG II are lower in diabetes. Conclusions. Diabetes in rats led to preference toward deleterious (ANG II, ANG III) over protective (ANG IV, ANG (1–9), and ANG (1–7)) ANG I metabolites. PMID:27803936

  20. Therapeutic potential of sulindac against ischemia-reperfusion-induced myocardial infarction in diabetic and nondiabetic rats

    PubMed Central

    Annapurna, Akula; Challa, Siva Reddy; Prakash, Gomedhikam J; Viswanath, Routhu Kasi

    2008-01-01

    BACKGROUND Diabetes mellitus is an independent risk factor for cardiovascular disease and is also associated with increased susceptibility to cardiovascular complications. It has been suggested that alterations in glucose metabolism and glucose flux via the aldose reductase pathway make the diabetic heart more sensitive to ischemic-reperfusion injury. Previous studies have found sulindac to have inhibitory and anti-inflammatory effects on aldose reductase. The use of aldose reductase inhibitors for the protection of ischemic myocardium is still in an exploratory state. OBJECTIVES To evaluate the therapeutic potential of sulindac in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h) in diabetic and nondiabetic rats. METHODS Diabetes was induced in rats by administering streptozotocin (45 mg/kg, intravenously). Myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Sorbitol dehydrogenase levels in heart tissue, as well as lipid peroxide levels in serum and heart tissue, were estimated spectrophotometrically. RESULTS Infarct size was increased in diabetic rats in comparison with normal rats. Pretreatment with sulindac significantly reduced infarct size, lipid peroxidation and sorbitol dehydrogenase levels in both diabetic and nondiabetic rats. The degree of cardioprotection was greater in diabetic rats than in nondiabetic rats. CONCLUSIONS The present study indicates that the observed cardioprotection provided by sulindac in terms of reducing infarct size in normal rats may be due to its combined antioxidant and anti-inflammatory activities. The inhibition of aldose reductase may be responsible for the enhanced cardioprotection observed in diabetic rats treated with sulindac. PMID:19343118

  1. Therapeutic potential of sulindac against ischemia-reperfusion-induced myocardial infarction in diabetic and nondiabetic rats.

    PubMed

    Annapurna, Akula; Challa, Siva Reddy; Prakash, Gomedhikam J; Viswanath, Routhu Kasi

    2008-01-01

    Diabetes mellitus is an independent risk factor for cardiovascular disease and is also associated with increased susceptibility to cardiovascular complications. It has been suggested that alterations in glucose metabolism and glucose flux via the aldose reductase pathway make the diabetic heart more sensitive to ischemic-reperfusion injury. Previous studies have found sulindac to have inhibitory and anti-inflammatory effects on aldose reductase. The use of aldose reductase inhibitors for the protection of ischemic myocardium is still in an exploratory state. To evaluate the therapeutic potential of sulindac in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h) in diabetic and nondiabetic rats. Diabetes was induced in rats by administering streptozotocin (45 mg/kg, intravenously). Myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Sorbitol dehydrogenase levels in heart tissue, as well as lipid peroxide levels in serum and heart tissue, were estimated spectrophotometrically. Infarct size was increased in diabetic rats in comparison with normal rats. Pretreatment with sulindac significantly reduced infarct size, lipid peroxidation and sorbitol dehydrogenase levels in both diabetic and nondiabetic rats. The degree of cardioprotection was greater in diabetic rats than in nondiabetic rats. The present study indicates that the observed cardioprotection provided by sulindac in terms of reducing infarct size in normal rats may be due to its combined antioxidant and anti-inflammatory activities. The inhibition of aldose reductase may be responsible for the enhanced cardioprotection observed in diabetic rats treated with sulindac.

  2. Histological study on the protective role of vitamin B complex on the cerebellum of diabetic rat.

    PubMed

    Eltony, Sohair A

    2016-08-01

    Disorder in cerebellar structure was reported in diabetes mellitus. B vitamins are involved in many significant metabolic processes within the brain. To detect the protective role of vitamin B complex on the histological structure of the cerebellum of experimentally induced diabetic rat. Eighteen adult male Wistar rats were divided into two groups. Group I: normal vehicle control (n=6). Group II: streptozotocin-induced diabetic rats (n=12), which was equally divided into two subgroups; IIA (diabetic vehicle control), IIB (diabetic vitamin B complex-treated): streptozotocin-induced diabetic rats treated with vitamin B complex (1mg/kg/day) for 6 weeks. Specimens from the cerebellum were processed for light and electron microscopy. In vitamin B complex treated group, the histological changes in Purkinje cells, astrocytes and oligodendrocytes were improved compared with the diabetic non-treated group. The white matter revealed intact myelinated axons. Inducible nitric oxide synthase (iNOS) and caspase-3 expression reduced. Glial fibrillary acidic protein (GFAP) expression revealed less activated astroglia. The number of Purkinje cells/mm(2) significantly increased. While, the number of GFAP positive astrocytes/mm(2) significantly decreased. In addition, the blood glucose level was reduced. Vitamin B complex protected the cerebellum from the histological changes which occurred in STZ- induced diabetic rats. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Comparison between the effect of glibenclamide and captopril on experimentally induced diabetic nephropathy in rats.

    PubMed

    Akbar, Daad H; Hagras, Magda M; Amin, Hanan A; Khorshid, Omayma A

    2013-06-01

    This study aimed to elucidate the role of glibenclamide in the prevention of diabetic nephropathy and to compare it with a reference drug captopril in rats. There were two main groups of rats. Control group (I) was subdivided into four subgroups which received distilled water, vehicle of streptozotocin, glibenclamide or captopril. The streptozotocin-diabetic Group (II) was subdivided into three subgroups: untreated, glibenclamide or captopril treated. Measurement of arterial blood pressure, serum glucose and creatinine levels, 24 h urinary protein and albumin/creatinine ratio, kidney weight and its histological examination were done after 1, 2, 4, 8, 12 and 16 weeks of treatment. In treated diabetic rats captopril reduced blood pressure significantly, while no significant change in the mean arterial blood pressure or blood glucose level was recorded with glibenclamide treatment. Glibenclamide and captopril-treated diabetic rats showed significant decrease in serum creatinine level, urine volume, urinary protein excretion, albumin:creatinine ratio and kidney:body weight ratio compared with the diabetic non-treated group. Histological examination of diabetic kidneys treated with either glibenclamide or captopril showed reduced glomerular hypertrophy, glomerulosclerosis, tubular degeneration and interstitial fibrosis compared with untreated diabetic rats. Glibenclamide attenuated some biochemical and histological changes produced by diabetic nephropathy, despite persistent hyperglycemia and hypertension.

  4. Opposing effects of NaCl restriction and carbohydrate loading on urine volume in diabetic rats.

    PubMed

    O'Neill, H A; Kwon, T-H; Ring, T; Dimke, H; Lebeck, J; Frøkiaer, J; Collins, P B; Nielsen, S; Frische, S

    2011-05-01

    To test the effects of dietary NaCl and carbohydrate content on urine volume in diabetic rats. Streptozotocin-induced diabetic rats were subjected to NaCl restriction using either a NaCl-deficient carbohydrate-rich synthetic diet (Altromin C1036) supplemented to contain 0.16% NaCl (C1036 + lowNaCl) or a modified normal cereal-based diet (Altromin 1320) containing 0.086% NaCl (lowNaCl-1320). Normal diet contained 0.2683% NaCl. Using the C1036 + lowNaCl diet, earlier reported paradoxical increases in water intake and urine volume of diabetic rats were reproduced. However, water intake and urine volume also increased in diabetic rats offered the synthetic C1036 diet supplemented with NaCl to normal levels. Using the lowNaCl-1320 diet, water intake and urine volume were markedly reduced. Highly significant correlations between urine volume and both osmotic output and urinary glucose excretion were found in diabetic rats on normal diet, but these correlations were absent in diabetic rats on synthetic diet, which showed higher urine volumes than expected from the correlations. In contrast, urine volume was significantly correlated with carbohydrate intake in diabetic rats, irrespective of the diet. (i) The synthetic diet dramatically increases the urine volume in STZ-DM rats irrespectively of NaCl content. (ii) Rats with STZ-DM on a normal diet show reduced water intake and urine volume in response to dietary NaCl restriction. (iii) A shift to high carbohydrate diet induces polyuria in STZ-DM rats. (iv) Urine volume in all STZ-DM rats only shows correlation with dietary carbohydrate intake. (v) Glucose-driven osmotic diuresis is unlikely to explain the carbohydrate-induced polyuria. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

  5. Limbs' postischemic revascularization is not improved by losartan treatment in diabetic rats.

    PubMed

    Fallahzadeh, A; Khazaei, M

    2014-01-01

    Most physiological actions of angiotensin II (Ang II) on cardiovascular system are mediated by angiotensin type 1 receptor (AT1R). Since peripheral artery disease is one of the most important complications of diabetes, in this study, we aimed to investigate the effect of losartan, an AT1R blocker, on skeletal muscle angiogenesis in diabetic hind limb ischemic rats. Twenty four male Wistar rats were randomly divided into four groups as follow: diabetic sham; diabetic sham + losartan (15 mg/kg/day); diabetic hindlimb ischemia; diabetic hindlimb ischemia + losartan. For induction of diabetes, streptozotocin was injected (55 mg/kg; i.p.). The animals were sacrificed after 21 days and the serum concentrations of vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sFlt-1), nitric oxide (NO), capillary density, and capillary to fiber (cap⁄fib) ratio in ischemic legs were evaluated. The serum NO concentrations were significantly decreased, sFlt-1 concentrations increased, and VEGF concentrations did not significantly change after experiment in diabetic sham and diabetic hind limb ischemic rats. Administration of losartan did not induce significant changes in serum NO, sFlt-1, and VEGF concentrations (p>0.05). Capillary density and cap⁄fib ratio in ischemic leg of diabetic rats were not affected by losartan treatment (p>0.05). AT1R blocker, losartan, was not able to restore neovascularization in the ischemic leg of diabetic animals. Therefore, based on the present data, the losartan cannot be considered for treatment or prevention of peripheral artery disease in diabetic subjects.

  6. Carvedilol protected diabetic rat hearts via reducing oxidative stress

    PubMed Central

    Huang, He; Shan, Jiang; Pan, Xiao-hong; Wang, Hui-ping; Qian, Ling-bo

    2006-01-01

    Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has close connection with antioxidant stress destruction in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant properties. To study the effect of carvedilol on the antioxidant status in diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage carvedilol-administered for 5 weeks, hemodynamic parameters, the levels of malondialdehyde, activities of antioxidant enzymes and expression of Bcl-2 mRNA in the cardiac tissues were measured. The diabetic rats not only had cardiac disfunction, weaker activities of antioxidant enzymes, but also showed lower expression of Bcl-2. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicated that carvedilol partly improves cardiac function via its antioxidant properties in diabetic rats. PMID:16909474

  7. Major histocompatibility complex gene product expression on pancreatic beta cells in acutely diabetic BB rats.

    PubMed Central

    Issa-Chergui, B.; Yale, J. F.; Vigeant, C.; Seemayer, T. A.

    1988-01-01

    Type I diabetes mellitus was induced in young, diabetes-prone BB rats by the passive transfer of concanavalin A-activated T lymphocytes from the spleens of acutely diabetic BB rats. The pancreas of the recipients was examined 1-2 days after the onset of glycosuria by immunocytochemistry by means of monoclonal antibodies for determining whether 1) Class I and/or II major histocompatibility gene complex (MHC) products were expressed on beta cells and 2) the mononuclear cell infiltrates were represented by T cells. Marked expression of Class I MHC gene products was evident on beta cells. In contrast, Class II MHC gene products were not identified on normal-appearing beta cells. Dendritic cells dispersed throughout the acinar and interstitial pancreas were markedly increased in number. The mononuclear cell infiltrate contained few cells (1-15%) recognized by a pan-T cell marker. Although it is possible that this passive transfer model might differ considerably from the spontaneously occurring diabetic state in the rat, this study suggests that 1) Class I, rather than Class II, MHC gene expression may be pivotal to beta-cell injury in diabetic rats, and 2) non-T cells may constitute an effector cell population central to beta-cell necrosis in Type I diabetes mellitus. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3276208

  8. Control of glomerular hypertension by insulin administration in diabetic rats.

    PubMed Central

    Scholey, J W; Meyer, T W

    1989-01-01

    Micropuncture studies were performed in Munich Wistar rats made diabetic with streptozotocin and in normal control rats. Diabetic rats received daily ultralente insulin to maintain moderate hyperglycemia (approximately 300 mg/dl). Group 1 diabetic rats studied after routine micropuncture preparation exhibited elevation of the single nephron glomerular filtration rate (SNGFR) due to increases in the glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In group 2 diabetic rats infusion of insulin to achieve acute blood glucose control normalized the glomerular transcapillary pressure gradient while increasing the glomerular ultrafiltration coefficient, so that SNGFR remained elevated. Persistent elevation of SNGFR despite normalization of the transcapillary pressure gradient was also observed in group 3 diabetic rats infused with insulin plus sufficient dextrose to maintain hyperglycemia. These studies indicate that glomerular capillary hypertension in diabetes is an acutely reversible consequence of insulin deficiency and not the result of renal hypertrophy. PMID:2649514

  9. Azilsartan improves glycemic status and reduces kidney damage in zucker diabetic fatty rats.

    PubMed

    Hye Khan, Md Abdul; Neckář, Jan; Haines, Jasmine; Imig, John D

    2014-08-01

    Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, demonstrates antihypertensive and organ protective effects in hypertension. We investigated the efficacy of AZL-M to ameliorate metabolic syndrome and kidney damage associated with type 2 diabetes using Zucker diabetic fatty (ZDF) rats. ZDF rats were treated with vehicle or AZL-M for 8 weeks. Zucker diabetic lean (ZDL) rats were used as controls. Urine and plasma samples were collected for biochemical analysis, and kidney tissues were used for histopathological and immunohistopathological examination at the end of the 8-week protocol. ZDF rats were diabetic with hyperglycemia and impaired glucose tolerance, and AZL-M ameliorated the diabetic phenotype. ZDF rats were hypertensive compared with ZDL rats (181±6 vs. 129±7mm Hg), and AZL-M decreased blood pressure in ZDF rats (116±7mm Hg). In ZDF rats, there was marked renal damage with elevated proteinuria, albuminuria, nephrinuria, 2-4-fold higher tubular cast formation, and glomerular injury compared with ZDL rats. AZL-M treatment reduced renal damage in ZDF rats. ZDF rats demonstrated renal inflammation and oxidative stress with elevated urinary monocyte chemoattractant protein 1 excretion, renal infiltration of macrophages, and elevated kidney malondialdehyde levels. AZL-M reduced oxidative stress and inflammation in ZDF rats. Overall, we demonstrate that AZL-M attenuates kidney damage in type 2 diabetes. We further demonstrate that anti-inflammatory and antioxidative activities of AZL-M contribute to its kidney protective action. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Evaluation of Effect of Nishamalaki on STZ and HFHF Diet Induced Diabetic Neuropathy in Wistar Rats

    PubMed Central

    Pandit, Vijaya Anil; Bhosale, Madhura Shirish Kumar; Khatavkar, Pallawi Shashank

    2016-01-01

    Introduction Diabetic neuropathy is one of the most common complications affecting 50% of diabetic patients. Neuropathic pain is the most difficult types of pain to treat. There is no specific treatment for neuropathy. Nishamalaki (NA), combination of Curcuma longa and Emblica officinalis used to treat Diabetes Mellitus (DM). So, efforts were made to test whether NA is useful in prevention of diabetic neuropathy. Aim To evaluate the effect of NA on diabetic neuropathy in type 2 diabetic wistar rats. Materials and Methods Group I (Control) vehicle treated consists of 6 rats. Diabetes induced in 36 wistar rats with Streptozotocin (STZ) (35mg/kg) intra-peritoneally followed by High Fat High Fructose diet. After confirmation of development of diabetes; rats divided into six groups (n=6). Group II – VII Diabetic Control, NA low dose, NA High dose, Glibenclamide, Pioglitazone and Epalrestat. Animals received drug treatment for next 12 weeks. Monitoring of Blood Sugar Level (BSL) done every 15 days and lipid profile at the end. Eddy’s hot plate and tail immersion test performed to assess thermal hyperalgesia and cold allodynia. Walking function test performed to assess motor function. Results Diabetic rats exhibited significant (p<0.001) hyperalgesia and increased BSL compared to control rats. Dose-dependent improvement was observed in thermal hyperalgesia & cold allodynia in NA groups. Activity of NA was more than Glibenclamide, Epalrestat and Pioglitazone in high dose and comparable in low dose. Nishamalaki improved lipid profile. Conclusion Apart from controlling hyperglycaemia and reducing lipid levels, NA effectively prevented the development of diabetic neuropathy. PMID:27891351

  11. Effect of hydroalcoholic Allium ampeloprasum extract on oxidative stress, diabetes mellitus and dyslipidemia in alloxan-induced diabetic rats.

    PubMed

    Rahimi-Madiseh, Mohammad; Heidarian, Esfandiar; Kheiri, Soleiman; Rafieian-Kopaei, Mahmoud

    2017-02-01

    Allium ampeloprasum (AA) is a medicinal plant which is used in Iranian traditional medicine to treat or prevent different diseases. The aim of this study is to investigate the effect of AA extract on oxidative stress and dyslipidemia in diabetic rats induced by alloxan. In this experimental study, 60 male Wistar rats weighing 200-250gr were randomly divided to five groups of 12 each including healthy control (group I), diabetic control (group II), metformin-treated diabetic positive control (group III) and two groups treated with doses 400 (group IV) and 800 (groupV) mg/kg/BW of AA extracts. Diabetes mellitus was experimentally induced by injection of two doses of alloxan-120 and 65mg/kg-within two consecutive days. Alloxan-induced diabetes caused significant increase in serum glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and high density lipoprotein (HDL) levels in group II (p<0.05). Furthermore, serum malondialdehyde (MDA) levels increased significantly and liver catalase activity decreased significantly in the 2nd group compared to 1st control; respectively p=0.0001 and p=0.009. In the group IV has seen a significant decrease in serum TG (p=0.01), TC (p=0.0001), VLDL (p=0.01), and MDA (p=0.0001) levels and significant increase in the liver and kidney catalase activities of the rats compared to the group II; respectively p=0.0001 and p=0.0001. In Conclusion our results highlight potentially relevant health beneficial effects of AA extract which exerts hypoglycemic, hypolipidemic, and anti-oxidative stress effects in rats with alloxan-induced diabetes. Therefore, it may be considered as useful dietary supplements in diabetic patients.

  12. Choline treatment affects the liver reticuloendothelial system and plasma fatty acid composition in diabetic rats.

    PubMed

    Al-Saeedi, Fatma J; Cheng, Behling

    2013-07-01

    This study investigated effects of choline treatment on hepatic reticuloendothelial and biliary functions and plasma fatty acid composition in diabetic rats. Diabetes was induced by streptozotocin (STZ). Choline was administered to untreated rats and a portion of STZ-treated rats for two sequences of five consecutive days, separated by a 2-day interval. Hepatic functions were studied using (99m) Tc Tin (II) colloid (TIN) and 99 mTc mebrofenin [bromo-iminodiacetic acid (BrIDA)] imaging. The TIN-uptake ratios (organ/whole body) of heart, liver and spleen, and the BrIDA-uptake ratios (organ or tissue/whole body) of liver, biliary tree and abdomen were obtained following imaging studies. Fatty acids were analysed by GC/MS. Choline treatment did not attenuate hyperglycaemic development. Diabetic rats showed (i) a decreased TIN-uptake ratio in liver with co-increased ratios in heart and spleen; choline treatment diminished these changes, (ii) elevated BrIDA-uptake ratios in biliary tree and abdomen but not in liver; choline treatment did not attenuate the elevations and (iii) decreases in plasma palmitoleic acid and oleic acid, reflecting an impaired stearoyl-CoA desaturase function; choline treatment did not affect the diminutions, but caused a decrease in arachidonic acid with a co-increase in linoleic acid. Some rats developed hypoproteinemia (HPO). HPO rats also exhibited decreases in plasma palmitoleic acid and oleic acid. Diabetes caused almost absence of palmitoleic acid in HPO rats. Choline treatment exerted no effect on the plasma fatty acid composition of diabetic HPO rats. Choline treatment affected hepatic reticuloendothelial function and plasma fatty acid composition, but not hepatobiliary function, in diabetic rats. Whether choline treatment is beneficial requires further studies. © 2013 The Authors Clinical Physiology and Functional Imaging © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  13. Chronic treatment with qiliqiangxin ameliorates aortic endothelial cell dysfunction in diabetic rats.

    PubMed

    Chen, Fei; Wu, Jia-Le; Fu, Guo-Sheng; Mou, Yun; Hu, Shen-Jiang

    2015-03-01

    Qiliqiangxin (QL), a traditional Chinese medicine, has been shown to be beneficial for chronic heart failure. However, whether QL can also improve endothelial cell function in diabetic rats remains unknown. Here, we investigated the effect of QL treatment on endothelial dysfunction by comparing the effect of QL to that of benazepril (Ben) in diabetic Sprague-Dawley rats for 8 weeks. Cardiac function was evaluated by echocardiography and catheterization. Assays for acetylcholine-induced, endothelium-dependent relaxation (EDR), sodium nitroprusside-induced endothelium-independent relaxation, serum nitric oxide (NO), and nitric oxide synthase (NOS) as well as histological analyses were performed to assess endothelial function. Diabetic rats showed significantly inhibited cardiac function and EDR, decreased expression of serum NO and phosphorylation at Ser(1177) on endothelial NOS (eNOS), and impaired endothelial integrity after 8 weeks. Chronic treatment for 8 weeks with either QL or Ben prevented the inhibition of cardiac function and EDR and the decrease in serum NO and eNOS phosphorylation caused by diabetes. Moreover, either QL or Ben suppressed inducible NOS (iNOS) protein levels as well as endothelial necrosis compared with the diabetic rats. Additionally, QL prevented the increase in angiotensin-converting enzyme 1 and angiotensin II receptor type 1 in diabetes. Thus, chronic administration of QL improved serum NO production, EDR, and endothelial integrity in diabetic rat aortas, possibly through balancing eNOS and iNOS activity and decreasing renin-angiotensin system expression.

  14. Current-modulated electrical stimulation as a treatment for peripheral nerve regeneration in diabetic rats.

    PubMed

    Lin, Yu-Ching; Kao, Chia-Hong; Cheng, Yu-Kai; Chen, Jia-Jin J; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2014-01-01

    To study if electrical stimulation (ES) can be a useful tool to improve functional recovery after neuronal injury in the peripheral nervous system. We studied the effects of 2 Hz of percutaneous ES at different intensities of 1, 10 and 20 mA on peripheral nerve regeneration in rats with diabetes induced by streptozotocin. Non-stimulated diabetic rats were used as the sham-controls. A10-mm gap was made in the rat sciatic nerve by suturing the stumps into silicone rubber tubes and stimulation was carried out every other day for 3 weeks starting 1 week after surgery. After 4 weeks of recovery, the diabetic rats showed that ES of 1 mA or above could increase the cutaneous blood flow in their ipsilateral hindpaw to the injury. ES of 10 mA could improve the amplitude and the area of evoked muscle action potentials with faster target muscle reinnervation. ES of 10 mA could also ameliorate the calcitonin gene-related peptide expression in lamina I-II regions in the dorsal horn ipsilateral to the injury and the number of macrophages in the diabetic distal sciatic nerve. The impaired growth and maturation of regenerating axons in diabetic rat could be improved by ES of 10 mA or above. All these results lead to the conclusion that ES of 10 mA or above might be necessary to improve regeneration after a dissect lesion of the sciatic nerve in the diabetic rat.

  15. An Early Diagnostic Tool for Diabetic Peripheral Neuropathy in Rats

    PubMed Central

    Kambiz, Shoista; van Neck, Johan W.; Cosgun, Saniye G.; van Velzen, Marit H. N.; Janssen, Joop A. M. J. L.; Avazverdi, Naim; Hovius, Steven E. R.; Walbeehm, Erik T.

    2015-01-01

    The skin’s rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to investigate whether the skin rewarming rate in diabetic rats is related to microvascular changes and whether this is accompanied by changes observed in classical diagnostic methods for diabetic peripheral neuropathy. Computer-assisted infrared thermography was used to assess the rewarming rate after cold exposure on the plantar skin of STZ diabetic rats’ hind paws. Peripheral neuropathy was determined by the density of intra-epidermal nerve fibers (IENFs), mechanical sensitivity, and electrophysiological recordings. Data were obtained in diabetic rats at four, six, and eight weeks after the induction of diabetes and in controls. Four weeks after the induction of diabetes, a delayed rewarming rate, decreased skin blood flow and decreased density of IENFs were observed. However, the mechanical hyposensitivity and decreased motor nerve conduction velocity (MNCV) developed 6 and 8 weeks after the induction of diabetes. Our study shows that the skin rewarming rate is related to microvascular changes in diabetic rats. Moreover, the skin rewarming rate is a non-invasive method that provides more information for an earlier diagnosis of peripheral neuropathy than the classical monofilament test and MNCV in STZ induced diabetic rats. PMID:25984949

  16. Magnetic resonance imaging (MRI) and pathophysiology of the rat kidney in streptozotocin-induced diabetes

    SciTech Connect

    Lohr, J.; Mazurchuk, R.J.; Acara, M.A.; Nickerson, P.A.; Fiel, R.J. )

    1991-01-01

    Proton magnetic resonance imaging was performed on rats before induction of diabetes with streptozotocin (STZ) and at 2 and 12 days postinduction. Images revealed an increase in maximal longitudinal and axial dimensions of the kidneys at 2 days and a further increase at 12 days. Similarly, an increase in the size of the remaining kidney was seen in a rat which underwent uninephrectomy as a positive control. Two major differences were observed between the kidney undergoing compensatory hypertrophy and those developing diabetic nephropathy: (i) Expansion of the renal vasculature was seen only in images of the diabetic rat; (ii) A loss in conspicuity of the normal corticomedullary junction was seen in the T2-weighted images of the diabetic rat but not in the uninephrectomized rat. Histologic examination revealed that the medulla increased to a size greater than the cortex during diabetic nephropathy whereas the medullary volume was less than that of the cortex during compensatory hypertrophy. In vitro T1 relaxation times in cortex, outer medulla and inner medulla of kidneys from control rats were measured and compared with the same respective regions in diabetic rats. When these values were correlated with tissue water content, a linear increase in relaxation rate versus percent water content from cortex to inner medulla was found in the control kidneys, but this correlation was absent in diabetic nephropathy. These studies demonstrate that MRI is an effective noninvasive tool for studying the course of renal hypertrophy and hydration changes in the development of renal disease in STZ-induced diabetes in the rat.

  17. Boldine Prevents Renal Alterations in Diabetic Rats

    PubMed Central

    Hernández-Salinas, Romina; Vielma, Alejandra Z.; Arismendi, Marlene N.; Boric, Mauricio P.; Sáez, Juan C.; Velarde, Victoria

    2013-01-01

    Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50 mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100 µmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects. PMID:24416726

  18. [Effect of sulodexide on aortic vasodilation capacity and associated morphological changes in rats with streptozotocin-induced diabetes].

    PubMed

    Vásquez, José; Mathison, Yaira; Romero-Vecchione, Eduardo; Suárez, Claudia

    2010-12-01

    Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans (GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, i.v. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.

  19. Adipocyte dysfunction in rats with streptozotocin-nicotinamide-induced diabetes.

    PubMed

    Szkudelska, Katarzyna; Nogowski, Leszek; Szkudelski, Tomasz

    2014-04-01

    Administration of streptozotocin (STZ) and nicotinamide (NA) to adult rats allows for the induction of mild diabetes. However, this experimental model has not been fully characterized. This study was undertaken to determine the metabolic and secretory activity of adipose tissue in rats with STZ-NA-induced diabetes. Experiments were performed using epididymal adipocytes isolated from control and mildly diabetic rats. Lipogenesis, glucose transport as well as glucose and alanine oxidation, lipolysis, anti-lipolysis, cAMP levels and adipokine secretion were compared in cells isolated from the control and diabetic rats. Lipogenesis, glucose transport and oxidation were diminished in the adipocytes of diabetic rats compared with the fat cells of control animals. However, alanine oxidation appeared to be similar in the cells of non-diabetic and diabetic animals. Lipolytic response to low epinephrine concentrations was slightly increased in the adipocytes of diabetic rats; however, at higher concentrations of the hormone, lipolysis was similar in both groups of cells. The epinephrine-induced rise in cAMP levels was higher in the adipocytes of STZ-NA-induced diabetic rats, even in the presence of insulin. Lipolysis stimulated by dibutyryl-cAMP did not significantly differ, whereas anti-lipolytic effects of insulin were mildly decreased in the cells of diabetic rats. Secretion of adiponectin and leptin was substantially diminished in the adipocytes of diabetic rats compared with the cells of control animals. Our studies demonstrated that the balance between lipogenesis and lipolysis in the adipose tissue of rats with mild diabetes induced by STZ and NA is slightly shifted towards reduced lipid accumulation. Simultaneously, adiponectin and leptin secretion is significantly impaired. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

  20. Adipocyte dysfunction in rats with streptozotocin–nicotinamide-induced diabetes

    PubMed Central

    Szkudelska, Katarzyna; Nogowski, Leszek; Szkudelski, Tomasz

    2014-01-01

    Administration of streptozotocin (STZ) and nicotinamide (NA) to adult rats allows for the induction of mild diabetes. However, this experimental model has not been fully characterized. This study was undertaken to determine the metabolic and secretory activity of adipose tissue in rats with STZ-NA-induced diabetes. Experiments were performed using epididymal adipocytes isolated from control and mildly diabetic rats. Lipogenesis, glucose transport as well as glucose and alanine oxidation, lipolysis, anti-lipolysis, cAMP levels and adipokine secretion were compared in cells isolated from the control and diabetic rats. Lipogenesis, glucose transport and oxidation were diminished in the adipocytes of diabetic rats compared with the fat cells of control animals. However, alanine oxidation appeared to be similar in the cells of non-diabetic and diabetic animals. Lipolytic response to low epinephrine concentrations was slightly increased in the adipocytes of diabetic rats; however, at higher concentrations of the hormone, lipolysis was similar in both groups of cells. The epinephrine-induced rise in cAMP levels was higher in the adipocytes of STZ-NA-induced diabetic rats, even in the presence of insulin. Lipolysis stimulated by dibutyryl-cAMP did not significantly differ, whereas anti-lipolytic effects of insulin were mildly decreased in the cells of diabetic rats. Secretion of adiponectin and leptin was substantially diminished in the adipocytes of diabetic rats compared with the cells of control animals. Our studies demonstrated that the balance between lipogenesis and lipolysis in the adipose tissue of rats with mild diabetes induced by STZ and NA is slightly shifted towards reduced lipid accumulation. Simultaneously, adiponectin and leptin secretion is significantly impaired. PMID:24628786

  1. Glucose production and storage in hepatocytes isolated from normal versus diabetic rats

    SciTech Connect

    Olivieri, M.C.; Dragland-Meserve, C.J.; Parker Botelho, L.H.

    1987-05-01

    The rates of glucose production and storage were compared in hepatocytes isolated from normal versus insulin-resistant diabetic rats. A single low-dose (40 mg/kg) IV injection of streptozotocin to 250 g rats resulted in a Type II diabetic animal model which was hyperglycemic with normal insulin levels. Addition of 8 mM /sup 14/C-lactate and 2 mM pyruvate to hepatocytes resulted in a linear increase in total glucose production (/sup 14/C-glucose and unlabeled glucose) and incorporation into glycogen measured over 120 min. The rate of gluconeogenesis was estimated from the production of /sup 14/C-glucose and the rate of glycogenolysis was estimated from the production of unlabeled glucose in cells incubated in the presence or absence of /sup 14/C-labelled substrate. There was not significant difference in total glucose production in hepatocytes isolated from normal versus diabetic rats, however, the contribution from gluconeogenesis versus glycogenolysis was significantly different. Following a 1 h incubation of cells from normal rats, 42% of the total glucose production was due to gluconeogenesis and 58% was due to glycogenolysis. In cells from diabetic rats, 83% of total glucose production was from gluconeogenesis and 17% from glycogenolysis. Also, incubation with /sup 14/C-lactate/pyruvate resulted in a 3.3-fold increase in /sup 14/C-glucose incorporation into glycogen in hepatocytes isolated from normal rats compared to diabetic rats. These data suggest that alterations occur in the rate-limiting enzymes responsible for glucose production and storage in hepatocytes isolated from a rat model of insulin-resistant Type II diabetes.

  2. Rosa damascena Mill. Essential Oil Has Protective Effect Against Testicular Damage in Diabetic Rats.

    PubMed

    Hamedi, Somayeh; Shomali, Tahoora; Haghighat, Aliakbar

    2017-08-09

    This study investigates the protective effect of Rosa damascena essential oil on diabetes-induced testicular damage in rats. Thirty-six male Wistar rats were randomly divided into 6 equal groups: Group I: negative control (no treatment); Group II: positive control (diabetic by alloxan injection); Groups III-VI that rendered diabetic and received, respectively, 50, 100, 200, and 400 µg/kg/day rose oil, orally for 28 days. Rose oil did not significantly change body weight and blood glucose level as compared to positive control. Serum testosterone level of rose oil-treated rats remained statistically the same with both negative and positive control groups (Groups I and II). Rats treated with rose oil especially at 2 higher dosages (Groups V and VI) had higher sperm count and increased diameters of seminiferous tubules as compared to Group II. Rose oil even at the lowest dosage significantly increased cell count of spermatogonia, primary spermatocytes, Sertoli cells, and Leydig cells, with better outcomes for higher dosages. It appears that short-term repeated dose administration of rose oil can dose-dependently improve structural deteriorations of testes and epididymal sperm count in diabetic rats.

  3. Ulcer healing potential of ethanolic extract of Caralluma attenuata on experimental diabetic rats

    PubMed Central

    Garg, Sunil; Srivastava, Sajal; Singh, Kisanpal; Sharma, Alok; Garg, Kavita

    2016-01-01

    Introduction: Available data indicated that diabetes mellitus (DM) increases the vulnerability of the gastric ulcers and the need of the hour is to develop effective agents to treat ulcer with diabetes for better patient compliance and cost effectiveness. The ulcer-healing properties of ethanolic extract of Caralluma attenuata (CAEt) against both chemically- and physically induced gastric ulcers in experimental rats are recently studied. Aim: To assess the ulcer healing potential of Ethanolic Extract of Caralluma attenuata on Experimental Diabetic Rats. Material and Methods: The current study aimed to evaluate ulcer healing properties of CAEt on the aspirin induced gastric ulcer in rats with streptozotocin induced DM. The hypothesis is based on the fact that DM results in compromising the mucosal defensive factors associated with delay in gastric ulcer healing, and if these changes can be corrected by using agents known for their antidiabetic and antiulcer properties. Experimental albino rats were divided into six groups. Except for Group I, other groups contained streptozotocin-induced diabetic rats. Group I (normal control) and Group II (diabetic control) were administered vehicle, Groups III and IV (diabetic experimental) were administered CAEt in dose of 100 mg/kg and 250 mg/kg, respectively, and Groups V and VI (positive controls) were respectively administered oral standard drugs omeprazole, 20 mg/kg, and tolbutamide 10 mg/kg. Result: The results confirmed that the CAEt significantly decreases the ulcer index (P < 0.05) in the aspirin-induced gastric ulcers and also significantly exhibit antioxidant and glucose lowering activity in the diabetic ulcer rats. The study showed that C. attenuata has the potential to be used as an antiulcer agent in experimental diabetic rats. PMID:27621520

  4. Ulcer healing potential of ethanolic extract of Caralluma attenuata on experimental diabetic rats.

    PubMed

    Garg, Sunil; Srivastava, Sajal; Singh, Kisanpal; Sharma, Alok; Garg, Kavita

    2016-01-01

    Available data indicated that diabetes mellitus (DM) increases the vulnerability of the gastric ulcers and the need of the hour is to develop effective agents to treat ulcer with diabetes for better patient compliance and cost effectiveness. The ulcer-healing properties of ethanolic extract of Caralluma attenuata (CAEt) against both chemically- and physically induced gastric ulcers in experimental rats are recently studied. To assess the ulcer healing potential of Ethanolic Extract of Caralluma attenuata on Experimental Diabetic Rats. The current study aimed to evaluate ulcer healing properties of CAEt on the aspirin induced gastric ulcer in rats with streptozotocin induced DM. The hypothesis is based on the fact that DM results in compromising the mucosal defensive factors associated with delay in gastric ulcer healing, and if these changes can be corrected by using agents known for their antidiabetic and antiulcer properties. Experimental albino rats were divided into six groups. Except for Group I, other groups contained streptozotocin-induced diabetic rats. Group I (normal control) and Group II (diabetic control) were administered vehicle, Groups III and IV (diabetic experimental) were administered CAEt in dose of 100 mg/kg and 250 mg/kg, respectively, and Groups V and VI (positive controls) were respectively administered oral standard drugs omeprazole, 20 mg/kg, and tolbutamide 10 mg/kg. The results confirmed that the CAEt significantly decreases the ulcer index (P < 0.05) in the aspirin-induced gastric ulcers and also significantly exhibit antioxidant and glucose lowering activity in the diabetic ulcer rats. The study showed that C. attenuata has the potential to be used as an antiulcer agent in experimental diabetic rats.

  5. Aberrant Activation of the Intrarenal Renin-Angiotensin System in the Developing Kidneys of Type 2 Diabetic Rats

    PubMed Central

    Fan, Y.-Y.; Kobori, H.; Nakano, D.; Hitomi, H.; Mori, H.; Masaki, T.; Sun, Y.-X.; Zhi, N.; Zhang, L.; Huang, W.; Zhu, B.; Li, P.; Nishiyama, A.

    2013-01-01

    We have previously reported that intrarenal angiotensin II (Ang II) levels are increased long before diabetes becomes apparent in obese Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a model of type 2 diabetes. In this study, we examined the changes in intrarenal renin-angiotensin system (RAS) activity in the developing kidneys of OLETF rats. Ang II contents and mRNA levels of RAS components were measured in male OLETF and control Long-Evans Tokushima (LETO) rats at postnatal days (PND) 1, 5, and 15, and at 4–30 weeks of age. In both LETO and OLETF rats, kidney Ang II levels peaked at PND 1, then decreased during the pre- and post-weaning periods. However, Ang II levels and gene expression of RAS components, including angiotensinogen (AGT), renin, and angiotensin-converting enzyme (ACE), were not significantly different between LETO and OLETF rats. Intrarenal Ang II contents further decreased during puberty (from 7 to 11 weeks of age) in LETO rats, bur not in OLETF rats. At 11 weeks of age, kidney Ang II levels, urinary AGT excretion, and mRNA levels of AGT and renin were higher in OLETF rats than in LETO rats, while blood glucose levels were not significantly different between these groups of rats. These data indicate that continued intrarenal expression of Ang II during pubescence contributes to the increases in intrarenal Ang II levels in prediabetic OLETF rats, and is associated with increased intrarenal AGT and renin expression. Inappropriate activation of the intrarenal RAS in the prediabetic stage may facilitate the onset and development of diabetic nephropathy in later life. PMID:23322513

  6. Dual therapy of vildagliptin and telmisartan on diabetic nephropathy in experimentally induced type 2 diabetes mellitus rats.

    PubMed

    Sharma, Ashish Kumar; Kanawat, Devendra Singh; Mishra, Akanksha; Dhakad, Prashant Kumar; Sharma, Prashant; Srivastava, Varnika; Joshi, Sneha; Joshi, Megha; Raikwar, Sachin Kumar; Kurmi, Muneem Kumar; Srinivasan, Bharthu Parthsarthi

    2014-12-01

    The objective of this article is to investigate the combination of telmisartan with vildagliptin therapy versus monotherapy of vildagliptin and telmisartan on diabetic nephropathy in type 2 diabetes mellitus rats. In adult rats streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg) were injected intraperitoneally to produce diabetic nephropathy. Rats of either sex allotted to the following groups: (i) triple therapy: metformin (120 mg/kg, o.d.) + pioglitazone (1.25 mg/kg, o.d.) + glimepiride (0.7 mg/kg, o.d.); (ii) dual therapy: vildagliptin (8.76 mg/kg, o.d.) + telmisartan (6.48 mg/kg, o.d.); (iii) vildagliptin (8.76 mg/kg, o.d.); and (iv) telmisartan (6.48 mg/kg, o.d.); therapy was carried out for 35 days orally. Weekly at days 7, 14, 21, 28 and 35, blood pressure, blood glucose level, body weight, blood serum creatinine level, protein albumin level in urine, and blood urea nitrogen (BUN) were estimated. Renal structural changes were observed. Blood pressure, blood glucose level, blood serum creatinine level, protein albumin level in urine, BUN and renal deterioration increased significantly in diabetic rats compared with normal control rats. The vildagliptin + telmisartan treatment group showed no weight gain and controlled blood pressure, renovascular structural and biochemical parameters in diabetic neuropathy rats. The addition of telmisartan to vildagliptin demonstrated the best control over blood pressure, glycemia and diabetic nephropathy markers, renal structural changes and improvement of renal function as opposed to monotherapy with either drug, possibly because of the dual inhibitory effect on the renin-angiotensin system. © The Author(s) 2013.

  7. Type II vitamin D-dependent rickets with diabetic ketoacidosis.

    PubMed

    Sarkar, Sumantra; Mondal, Rakesh; Banerjee, Indira; Sabui, Tapas

    2013-01-01

    The high prevalence of vitamin D deficiency in relation to diabetes mellitus is well reported in the literature. However, type I diabetes mellitus (T1DM) in association with resistant rickets is extremely rare and reported in only one previous case. The authors describe here a case of type II vitamin D-dependent rickets (VDDR type II) in a 10-year-old Indian girl who presented with diabetic ketoacidosis (DKA). DKA as a presenting manifestation of T1DM in a patient with VDDR type II has never been reported before in worldwide literature.

  8. Dual Effect of Curcumin-Zinc Complex in Controlling Diabetes Mellitus in Experimentally Induced Diabetic Rats.

    PubMed

    Al-Ali, Khalil; Abdel Fatah, Hala Salah; El-Badry, Yaser Abdel-Moemen

    2016-01-01

    Ultrasound-assisted extraction of curcumin from Curcuma longa was performed in an ultrasonic bath at 30°C using ethanol for 40 min. A successful attempt has been made to prepare curcumin-zinc (Zn) complex using a simple chemical procedure. The complex formation and its stoichiometry were characterized using elemental analysis, Fourier transform (FT)-IR and UV spectroscopy which revealed the interaction of Zn(II) ion (M) with curcumin (ligand, L) to proceed via (ML) complex type formation. Oral administration of curcumin-Zn complex at a concentration of 150 mg/kg body weight/rat/d for 45 d in streptozotocin-induced diabetic rats in comparison to curcumin and/or Zn administration exerted a hypoglycemic effect. A significant reduction in blood glucose, glycosylated hemoglobin (Hb)A1c, and lipid profile parameters with an excellent improvement in plasma insulin levels have been attained. Also, the reduced activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine in the diabetic rats treated with the complex exhibited the non-toxic nature of the curcumin-Zn complex. Finally, the larger extent of the complex in hyperglycemic improvement in comparison to curcumin and/or Zn supplementation was interpreted by its dual action on glucose and insulin maintenance.

  9. [Spirulina, exercise and serum glucose control in diabetic rats].

    PubMed

    Moura, Leandro Pereira de; Gurjão, André Luiz Demantova; Jambassi Filho, José Claudio; Mizuno, Julio; Suemi, Clara; Mello, Maria Alice Rostom de

    2012-02-01

    The objective of this study was to analyze the effect of Spirulina and/or exercise training in the control of serum glucose homeostasis in diabetic rats. Young Wistar rats were induced to diabetes by intravenous alloxan administration and separated into four groups: diabetic control (DC), diabetic Spirulina (DS), diabetic exercise (DE) and diabetic exercise Spirulina (DES). There were no differences between groups with respect to: body weight, food intake, glucose tolerance, insulin tolerance and blood lactate concentrations during a swimming effort test. DS group showed lower insulin concentrations when compared with DC (pancreas) and DE and DES (serum). The protocols of exercise and supplementation with Spirulina used in the present study were not able to improve serum glucose homeostasis in diabetic rats.

  10. Yacon roots (Smallanthus sonchifolius) improve oxidative stress in diabetic rats.

    PubMed

    Habib, Natalia C; Serra-Barcellona, Carolina; Honoré, Stella M; Genta, Susana B; Sánchez, Sara S

    2015-08-01

    Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson, Asteraceae (yacon) roots are a natural product recognized by the traditional medicine to treat diabetes-related problems. There are no reports concerning the potential of yacon roots to reduce oxidative stress and ameliorate diabetes complications in diabetic animals. This work analyzes the in vivo antioxidant activity and beneficial effects of yacon roots, using a model of streptozotocin-induced diabetes in rats. Lipid peroxidation and other indicators of oxidative stress were determined in liver and kidney homogenates from non-diabetic rats, untreated diabetic rats, and diabetic rats treated orally with yacon flour (340 mg fructooligosaccharide/kg/d) as a diet supplement for 90 d. Biochemical parameters were determined in liver, kidney, and blood at the end of the experimental period. Yacon supplementation to diabetic rats produced a significant decrease in malondialdehyde levels in both liver (-30.97%) and kidney (-19.15%). Hepatic superoxide dismutase and catalase activities were significantly lower in diabetic-treated rats (-13.46 and -64.33%, respectively) compared with diabetic controls. Similar results were observed in kidney. The treatment of diabetic rats produced an increase of glutathione peroxidase and glutathione levels in liver (172.50 and 35.91%, respectively) and kidney (177.78 and 57.76%, respectively). Plasma cholesterol and triacylglycerol levels and liver fatty acid composition, which were altered in diabetic rats, reverted back to nearly normal with yacon treatment. These results indicate that yacon root flour is a potential diet supplement with high in vivo antioxidant activity.

  11. Evaluation of anti-diabetic activity of glycyrrhizin-loaded nanoparticles in nicotinamide-streptozotocin-induced diabetic rats.

    PubMed

    Rani, Ruma; Dahiya, Shakti; Dhingra, Dinesh; Dilbaghi, Neeraj; Kim, Ki-Hyun; Kumar, Sandeep

    2017-08-30

    Glycyrrhizin is an active constituent of the roots and rhizomes of Glycyrrhiza glabra and has anti-hyperglycemic effects. In this study, nanoparticles (NPs) loaded with glycyrrhizin or metformin were evaluated in vivo for their anti-hyperglycemic potency towards type-II diabetes in rats. The NPs were produced via the ionotropic gelation method using the biocompatible polymers chitosan and gum arabic. The polymer concentration was optimized using the 3(2) factorial method to acquire both minimum particle size and maximum encapsulation efficiency. The NPs were then characterized with respect to particle size, encapsulation efficiency, stability, chemical interactions, and in vitro drug dissolution profiles using spectroscopic and microscopic analysis. Furthermore, glycyrrhizin and metformin and their nanoformulations were administered for 21 successive days to diabetic rats. Glycyrrhizin-loaded NPs had significant anti-diabetic effects even though they contained approximately one quarter of the dosage relative to the pure form. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Revealing the cost of Type II diabetes in Europe.

    PubMed

    Jönsson, B

    2002-07-01

    'The Cost of Diabetes in Europe - Type II study' is the first coordinated attempt to measure total healthcare costs of Type II (non-insulin-dependent) diabetes mellitus in Europe. The study evaluated more than 7000 patients with Type II diabetes in eight countries -- Belgium, France, Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom. A bottom-up, prevalence-based design was used, which optimised the collection of data at the national level while maintaining maximum international comparability. Effort was made to ensure consistency in terms of data specification, data collection tools and methods, sampling design, and the analysis and reporting of results. Results are reported for individual countries and in aggregate for the total study population. The total direct medical costs of Type II diabetes in the eight European countries was estimated at EUR 29 billion a year (1999 values). The estimated average yearly cost per patient was EUR 2834 a year. Of these costs, hospitalisations accounted for the greatest proportion (55%, range 30-65%) totalling EUR 15.9 billion for the eight countries. During the 6-month evaluation period, 13% of the Type II diabetic patients were hospitalised, with an average of 23 days in hospital projected annually. In contrast, drug costs for managing Type II diabetes were relatively low, with antidiabetic drugs and insulin accounting for only 7% of the total healthcare costs for Type II diabetes. Type II diabetes mellitus is a common disease and the prevalence is expected to increase considerably in the future, especially in developing countries. Current comprehensive economic data on the costs of diabetes are required for policy decisions to optimise resource allocation and to evaluate different approaches for disease management.

  13. Diabetes mitigates the recovery following intracranial hemorrhage in rats.

    PubMed

    Fan, Zhenzeng; Yuan, Yunchao; Wang, Feng; Qi, Yuepeng; Han, Haie; Wu, Jianliang; Zhang, Gengshen; Yang, Lijun

    2017-03-01

    Intracranial hemorrhage (ICH) is a common subtype of stroke with high morbidity and mortality. However, few studies have examined the effects of diabetes on the recovery from ICH-induced brain injury. Therefore, we examined the effects of diabetes on protein levels of aquaporins, neuronal loss, angiogenesis, blood brain barrier (BBB) integrity, and neurological deficits following intra-DH collagenase-induced ICH in the hippocampus. We found that diabetic rats exhibited enhanced AQP9 expression in the hippocampus relative to non-diabetic rats, which was associated with increased behavioral deficits. Additionally, ICH induced neovascularization, proliferation of brain microvascular endothelial cells, and hippocampal neuronal loss. However, ICH-induced neovascularization and proliferation of brain microvascular endothelial cells was severely impaired in diabetic rats. Furthermore, ICH-induced hippocampal neuronal loss was exaggerated in diabetic rats. Finally, ICH impaired BBB integrity in the ipsilateral hemisphere, which was increased in diabetic rats. Taken together, the attenuated brain angiogenesis, increased hippocampal neuronal loss, and impaired BBB integrity in diabetic rats after ICH were associated with enhanced AQP9 expression. This may suggest that AQP9 is one of the underlying mechanisms that can mitigate the recovery from ICH in diabetic populations.

  14. Flax and Pumpkin seeds mixture ameliorates diabetic nephropathy in rats.

    PubMed

    Makni, Mohamed; Sefi, Mediha; Fetoui, Hamadi; Garoui, El Mouldi; Gargouri, Nabil K; Boudawara, Tahia; Zeghal, Najiba

    2010-01-01

    This study investigated the hypoglycemic and antioxidant effects of Flax and Pumpkin seeds mixture on the kidney of alloxan-induced diabetic rats. Animals were allocated into three groups of six rats each: a control group (CD), a diabetic group (DD) and diabetic rats fed with Flax and Pumpkin seeds mixture (DMS) group. The DD rats showed a significant increase of glycemia and lipid parameters such as total lipid, total cholesterol and triglycerides levels compared to those of the control group (CD). In addition, plasma and kidney malonaldialdehyde levels (MDA) were significantly increased compared to (CD) group. Antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD) and non-enzymatic levels of reduced glutathione (GSH) significantly decreased in the plasma and kidney of diabetic rats compared to those of controls. Diet supplemented with Flax and Pumpkin seeds mixture ameliorated the antioxidant enzymes activities observed in diabetic rats and significantly decreased MDA levels. Kidney histological sections, showed glomerular hypertrophy and tubular dilatation. In DMS rats, these histopathological changes were less prominent. Our results suggest that Flax and Pumpkin seeds mixture supplemented in diet of diabetic rats may be helpful to prevent diabetes and its complications. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  15. Association of myelinated primary afferents impairment with mechanical allodynia in diabetic peripheral neuropathy: an experimental study in rats.

    PubMed

    Liao, Chenlong; Yang, Min; Zhong, Wenxiang; Liu, Pengfei; Zhang, Wenchuan

    2017-09-08

    To investigate the mechanisms underlying the efficacy of surgical treatment for painful diabetic peripheral neuropathy. Rats were initially divided into 3 groups (I, control rats, II, streptozotocin-induced diabetic rats, III, streptozotocin-induced diabetic rats with latex tube encircling the sciatic nerve without compression). When mechanical allodynia (MA) became stable in the third week, one third of group III rats were sacrificed and the remainder were further divided into subgroups depending on whether the latex tube was removed. Except for some rats in group III, all rats were sacrificed in the fifth week. Morphometric analysis of nerve fibers was performed. Expression level of GABAB receptor protein in spinal dorsal horn was determined. Changes of GABAB receptor within areas of primary afferents central terminal were identified. Chronic nerve compression caused by the interaction of diabetic nerves swelling and the encircling latex tube increased the incidence of MA in diabetic rats, and nerve decompression could ameliorate MA. In diabetic rats with MA, demyelination of myelinated fibers was noted and reduction of GABAB receptor was mainly detected in the area of myelinated afferent central terminals. MA in DPN should be partially attributed to compression impairment of myelinated afferents, supporting the rationale for surgical decompression.

  16. Crystal Structure of Rat Carnitine Palmitoyltransferase II (CPT-II)

    SciTech Connect

    Hsiao,Y.; Jogl, G.; Esser, V.; Tong, L.

    2006-01-01

    Carnitine palmitoyltransferase II (CPT-II) has a crucial role in the {beta}-oxidation of long-chain fatty acids in mitochondria. We report here the crystal structure of rat CPT-II at 1.9 Angstroms resolution. The overall structure shares strong similarity to those of short- and medium-chain carnitine acyltransferases, although detailed structural differences in the active site region have a significant impact on the substrate selectivity of CPT-II. Three aliphatic chains, possibly from a detergent that is used for the crystallization, were found in the structure. Two of them are located in the carnitine and CoA binding sites, respectively. The third aliphatic chain may mimic the long-chain acyl group in the substrate of CPT-II. The binding site for this aliphatic chain does not exist in the short- and medium-chain carnitine acyltransferases, due to conformational differences among the enzymes. A unique insert in CPT-II is positioned on the surface of the enzyme, with a highly hydrophobic surface. It is likely that this surface patch mediates the association of CPT-II with the inner membrane of the mitochondria.

  17. Depression among patients with type-II diabetes mellitus.

    PubMed

    Khan, Mohammad Akmal; Sultan, Sayed Mohammad; Nazli, Rubina; Akhtar, Tasleem; Khan, Mudasar Ahmad; Sher, Nabila; Aslam, Hina

    2014-10-01

    This study aimed to determine the frequency of depression among patients with type-II diabetes mellitus in Peshawar at Khyber Teaching Hospital, Peshawar, from March to September 2010. Depression was assessed by using Beck Depressive Inventory-II (BDI-II). Out of 140 patients with type-II diabetes, 85 (61%) were women and 55 (39%) were men. Mean age was 45±7.45 years. Eighty four (60%) patients presented with severe depression. Depression was higher in females than males and widows. Depression was high in diabetic patients, especially in females and widows. It is of essence that psychiatric attention may be necessary to be incorporated in diabetes care both for prevention and treatment.

  18. Intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats.

    PubMed

    Chen, Xiaofei; Zhao, Tong; Huang, Xin; Wu, Liying; Wu, Kuiwu; Fan, Ming; Zhu, Lingling

    2016-05-01

    Increasing studies have shown protective effects of intermittent hypoxia on brain injury and heart ischemia. However, the effect of intermittent hypoxia on blood glucose metabolism, especially in diabetic conditions, is rarely observed. The aim of this study was to investigate whether intermittent hypoxia influences blood glucose metabolism in type 1 diabetic rats. Streptozotocin-induced diabetic adult rats and age-matched control rats were treated with intermittent hypoxia (at an altitude of 3 km, 4 h per day for 3 weeks) or normoxia as control. Fasting blood glucose, body weight, plasma fructosamine, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), pancreas β-cell mass, and hepatic and soleus glycogen were measured. Compared with diabetic rats before treatment, the level of fasting blood glucose in diabetic rats after normoxic treatment was increased (19.88 ± 5.69 mmol/L vs. 14.79 ± 5.84 mmol/L, p < 0.05), while it was not different in diabetic rats after hypoxic treatment (13.14 ± 5.77 mmol/L vs. 14.79 ± 5.84 mmol/L, p > 0.05). Meanwhile, fasting blood glucose in diabetic rats after hypoxic treatment was also lower than that in diabetic rats after normoxic treatment (13.14 ± 5.77 mmol/L vs. 19.88 ± 5.69 mmol/L, p<0.05). Plasma fructosamine in diabetic rats receiving intermittent hypoxia was significantly lower than that in diabetic rats receiving normoxia (1.28 ± 0.11 vs. 1.39 ± 0.11, p < 0.05), while there were no significant changes in body weight, plasma insulin and β-cell mass. HOMA-IR in diabetic rats after hypoxic treatment was also lower compared with diabetic rats after normoxic treatment (3.48 ± 0.48 vs. 3.86 ± 0.42, p < 0.05). Moreover, intermittent hypoxia showed effect on the increase of soleus glycogen but not hepatic glycogen. We conclude that intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats and its regulation on muscular

  19. Knowledge Is Power: Teaching Children about Type II Diabetes

    ERIC Educational Resources Information Center

    Feild-Berner, Natalie; Balgopal, Meena

    2011-01-01

    World Diabetes Day (November 14) offers a wonderful opportunity to educate elementary children about the power they have to control their health. First lady Michelle Obama has urged Americans to educate themselves about childhood obesity, which is often associated with the onset of type II diabetes (Rabin 2010). The authors developed activities to…

  20. Knowledge Is Power: Teaching Children about Type II Diabetes

    ERIC Educational Resources Information Center

    Feild-Berner, Natalie; Balgopal, Meena

    2011-01-01

    World Diabetes Day (November 14) offers a wonderful opportunity to educate elementary children about the power they have to control their health. First lady Michelle Obama has urged Americans to educate themselves about childhood obesity, which is often associated with the onset of type II diabetes (Rabin 2010). The authors developed activities to…

  1. Type II (noninsulin-dependent) diabetes: new treatment options.

    PubMed

    Bodzin, B J

    1997-01-01

    Type II diabetes (noninsulin-dependent diabetes mellitus [NIDDM]) is a common primary and secondary diagnosis in home care patients. This article describes the pathophysiology of NIDDM, the new drugs that have been released for treatment, and the nursing implications inherent in using these new medications.

  2. Antidiabetic activity of Bauhinia forficata extracts in alloxan-diabetic rats.

    PubMed

    Lino, Cleide de Sousa; Diógenes, João Paulo Luz; Pereira, Bruno Azevedo; Faria, Rozilaine Aparecida Pelegrine Gomes; Andrade Neto, Manoel; Alves, Renata Sousa; de Queiroz, Maria Goreti Rodrigues; de Sousa, Francisca Cléa Florenço; Viana, Glauce Socorro Barros

    2004-01-01

    The antidiabetic activity of aqueous, ethanolic and hexanic extracts of Bauhinia forficata was investigated in a model of alloxan-induced diabetes in rats. The biochemical parameters studied were: plasma glucose, serum triglycerides, cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL). Extracts were administered daily for 7 d at doses of 200 and 400 mg/kg, p.o., 48 h after alloxan injection (60 mg/kg, i.v.). The alloxan-diabetic rats showed significant reductions in plasma glucose, triglycerides, total cholesterol and HDL-cholesterol after treatment with the extracts and glibenclamide (used as standard) as compared to the diabetic controls. Levels of LDL were not altered. In conclusion, our results showed that the plant extracts when administered by gavage may reduce glucose, triglycerides, total cholesterol and HDL-cholesterol levels. These results suggest the validity of the clinical use of B. forficata in the treatment of diabetes mellitus type II.

  3. Protein expression in salivary glands of rats with streptozotocin diabetes

    PubMed Central

    Mednieks, Maija I; Szczepanski, Andrew; Clark, Brett; Hand, Arthur R

    2009-01-01

    Diabetes mellitus (DM) is a widespread disease with high morbidity and health care costs. An experimental animal model was employed, using morphological and biochemical methods, to investigate the effects of DM on the expression and compartmentation of salivary gland proteins. The distribution of proline-rich proteins (PRP), submandibular mucin (Muc10) and the regulatory (RI and RII) subunits of cyclic AMP-dependent protein kinase type I and type II was determined in the parotid and submandibular (SMG) glands of rats treated with streptozotocin. Quantitative immunocytochemistry of secretory granules in diabetic glands revealed decreases of 30% for PRP in both the parotid and SMG, and a 40% decrease in Muc10 in the SMG. Immunogold labelling showed that RII decreased in nuclei and the cytoplasm in diabetic acinar cells while labelling of secretory granules was similar in control and diabetic parotid. Electrophoresis and Western blotting of tissue extracts of two secretory proteins showed that the response to DM and insulin treatment was gland specific: PRP showed little change in the SMG, but decreased in the parotid in DM and was partially restored after insulin treatment. Photoaffinity labelling showed only RI present in the SMG and mainly RII in the parotid. The results of this and previous studies demonstrating highly specific changes in salivary protein expression indicate that the oral environment is significantly altered by DM, and that oral tissues and their function can be compromised. These findings may provide a basis for future studies to develop tests using saliva for diabetic status or progression in humans. PMID:19659899

  4. Bauhinia variegata (Caesalpiniaceae) leaf extract: An effective treatment option in type I and type II diabetes.

    PubMed

    Kulkarni, Yogesh A; Garud, Mayuresh S

    2016-10-01

    Among various metabolic disorders, diabetes mellitus is one of the most common disorder. Present study was designed to evaluate the effectiveness of aqueous extract of Bauhinia variegata leaves (AE) in animal models of type I and type II diabetes. Type I diabetes was induced by streptozotocin at the dose of 55mg/kg (i.p.) in male Sprague Dawley rats while type II diabetes was induced by high fat diet and streptozotocin at the dose of 35mg/kg (i.p.). Diabetic animals were treated with AE at the dose of 250, 500 and 1000mg/kg. Glipizide (5mg/kg) was used as standard treatment drug. Treatment was given for 28days. Parameters evaluated were body weight, plasma glucose, cholesterol, triglyceride, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, total proteins, albumin, creatinine and bun urea nitrogen. In type II diabetes, high density lipoprotein levels in plasma and plasma insulin level were also evaluated. Histopathological study of pancreases were carried out in type I study. AE showed significant decrease in plasma glucose significantly. AE was also found to decrease cholesterol, triglyceride, creatinine and blood urea nitrogen level in both types of diabetes. AE did not show any significant effect on plasma levels of aspartate aminotransferase, alanine transaminase, alkaline phosphatase. AE was found to increase the albumin and total protein levels. Histopathological study showed that AE decreases the necrotic changes in the pancreatic tissue. Aqueous extract of B. variegata leaves was found effective in treatment of both type I and type II diabetes.

  5. Impaired Rhodopsin Generation in the Rat Model of Diabetic Retinopathy.

    PubMed

    Malechka, Volha V; Moiseyev, Gennadiy; Takahashi, Yusuke; Shin, Younghwa; Ma, Jian-Xing

    2017-10-01

    Diabetic retinopathy is a common complication of diabetes mellitus. Diabetic patients experience functional deficits in dark adaptation, contrast sensitivity, and color perception before microvascular pathologies become apparent. Herein, we evaluated early changes in neural retinal function and in retinoid metabolism in the eye in diabetes. Streptozotocin-induced diabetic rats showed decreased a- and b-wave amplitudes of scotopic and photopic electroretinography responses 4 months after diabetes induction compared to nondiabetic controls. Although Western blot analysis revealed no difference in opsin expression, rhodopsin content was decreased in diabetic retinas, as shown by a difference in absorbance. Consistently, levels of 11-cis-retinal, the chromophore for visual pigments, were significantly lower in diabetic retinas compared to those in controls, suggesting a retinoid deficiency. Among visual cycle proteins, interphotoreceptor retinoid-binding protein and stimulated by retinoic acid 6 protein showed significantly lower levels in diabetic rats than those in nondiabetic controls. Similarly, serum levels of retinol-binding protein 4 and retinoids were significantly lower in diabetic rats. Overall, these results suggest that retinoid metabolism in the eye is impaired in type 1 diabetes, which leads to deficient generation of visual pigments and neural retinal dysfunction in early diabetes. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Apoptosis, senescence, and autophagy in rat nucleus pulposus cells: Implications for diabetic intervertebral disc degeneration.

    PubMed

    Jiang, Libo; Zhang, Xiaolei; Zheng, Xuhao; Ru, Ao; Ni, Xiao; Wu, Yaosen; Tian, Naifeng; Huang, Yixing; Xue, Enxing; Wang, Xiangyang; Xu, Huazi

    2013-05-01

    This research was aimed to study the mechanisms by which diabetes aggravates intervertebral disc degeneration (IDD) and to discuss the relationship between autophagy and IDD in nucleus pulposus (NP) cells. Sixteen weeks after injecting streptozotocin (STZ), the intervertebral discs (IVDs) were studied by histology, Alcian blue, 1,9-dimethylmethylene blue (DMMB), immunohistochemistry, and RT-PCR to explore the IDD. The apoptosis and senescence of NP cells was investigated by terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, immunohistochemistry, and Western blot for caspase3, caspase8, caspase9, and p16lnk4A (increased in cellular senescence). The level of autophagy in NP cells was detected by Western blot, immunohistochemistry, and transmission electron microscopy (TEM). The proteoglycan and collagen II in the extracellular matrix and the aggrecan and collagen II mRNA expression in NP cells of diabetic rats were decreased compared with the control group. Diabetes increased apoptosis of NP cells and led to activations of initiators of intrinsic (caspases-9) and extrinsic (caspase-8) pathways as well as their common executioner (caspase-3). Cellular senescence was increased about twofold in NP of diabetic rats. In addition, the Western blot, immunohistochemistry, and TEM demonstrated higher level of autophagy in NP cells of diabetic rats than control rats to a statistically significant extent. These findings support that diabetes induced by STZ can cause IDD by accelerating the apoptosis and senescence of NP cells excluding the overweight influence. And the results suggest that the autophagy may be a response mechanism to the change of NP cells in diabetic rats. Copyright © 2012 Orthopaedic Research Society.

  7. Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats.

    PubMed

    Refaat, Rowaida; Sakr, Ahmed; Salama, Mona; El Sarha, Ashgan

    2016-09-01

    Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor-α (TNF-α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc.

  8. Ursolic Acid provides kidney protection in diabetic rats.

    PubMed

    Ling, Chen; Jinping, Lu; Xia, Li; Renyong, Yang

    2013-12-01

    Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes and the leading cause of end-stage renal failure. However, the treatment of DN is still a problem in the world. Inflammatory process plays a critical role in the development of DN. Therefore, anti-inflammatory treatment of DN is worth exploring now and in the future. The study aimed to evaluate the impact of ursolic acid (UA) on renal function in streptozotocin-induced diabetes. Rats with streptozotocin-induced diabetes were treated with UA for 16 weeks. After 16 weeks, urine albumin excretion, serum creatinine, and blood urea nitrogen were measured. In addition, renal oxidative stress level, nuclear factor kappa-B (NF-κB) activity, P-selectin expression, and kidney histopathologic changes were evaluated. Sixteen weeks following streptozotocin injection, the rats produced significant alteration in renal function and increased oxidative stress, NF-κB activity, and P-selectin expression in the kidneys. Interestingly, UA significantly prevented biochemical and histopathologic changes in the kidneys associated with diabetes. Compared with untreated diabetic rats, UA treatment lowered urine albumin excretion, renal oxidative stress level, NF-κB activity, and P-selectin expression. Moreover, UA treatment also improved renal histopathologic changes in rats with diabetes. UA treatment exhibited a protective effect on kidneys in diabetic rats, implying that UA could be a potential treatment for diabetic nephropathy.

  9. The Diabetic Nephropathy and the Development of Hypertension in Rats

    PubMed Central

    Zuccollo, Adriana; Navarro, Monica

    2001-01-01

    The present study was designed to examine the development of hypertension in diabetic rats treated with streptozotocin (STZ, 1mg/g bw). The rats were studied at 3, 6, 9, 12 and 15 weeks. From the third week the rats were divided in diabetic rats according their glycemias and controls, along 15 weeks. After the third week a group, of rats showed increased urinary protein excretion (93, 134, 155 and 191%) compared to controls. In this group of rats the urinary kallikrein excretion was lower than control and the systolic blood pressure became significantly elevated between 3 and 6 weeks and persisted up to 15 weeks. On the other hand a group of diabetic rats were normotensive with urinary protein excretion similar to controls and urinary kallikrein lower compared to control but significantly higher compared diabetic hypertensive rats. These data suggest that the association of progressive diabetic nephropathy with abnormal endothelium-dependent vasodilation may produce a high prevalence of hypertensive diabetes. PMID:12369707

  10. Orofacial sensory changes after streptozotocin-induced diabetes in rats.

    PubMed

    Nones, Carina Fernanda Mattedi; Reis, Renata Cristiane; Jesus, Carlos Henrique Alves; Veronez, Djanira Aparecida da Luz; Cunha, Joice Maria; Chichorro, Juliana Geremias

    2013-03-21

    Peripheral neuropathy is a common complication of diabetes and is often accompanied by episodes of pain. There is evidence that diabetic neuropathy may affect the trigeminal nerve, altering the transmission of orofacial sensory information. Structural changes in the trigeminal ganglia may be involved in the development of these sensory alterations. Herein, we evaluate the development of orofacial sensory changes after streptozotocin-induced diabetes in rats, and their sensitivity to pregabalin and morphine treatments. Furthermore, stereological analysis of the trigeminal ganglia was performed. Diabetic rats showed similar responses to 1% formalin applied into the upper lip compared to normoglycemic rats on weeks 1, 2 and 4 after streptozotocin. Additionally, there was no difference in the facial mechanical threshold of normoglycemic and diabetic rats, on weeks 1 up to 5 after streptozotocin, while the paw mechanical threshold of diabetic rats was significantly reduced. In contrast, diabetic rats developed long-lasting orofacial heat and cold hyperalgesia. Moreover, stereological analyses revealed significant neuronal loss in the trigeminal ganglia of diabetic compared to normoglycemic rats. Pregabalin treatment (30mg/kg, p.o.) of diabetic rats resulted in marked and prolonged (up to 6h) reduction of heat and cold orofacial hyperalgesia. Likewise, morphine treatment (2.5mg/kg, s.c.) abolished orofacial heat and cold hyperalgesia, but its effect was significant only up to 1h after the administration. In conclusion, the results of the present study demonstrated that streptozotocin-treated rats developed long-lasting orofacial heat and cold hyperalgesia, which is more amenable to reduction by pregabalin than morphine.

  11. Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats

    PubMed Central

    Mansouri, Esrafil; Khorsandi, Layasadat; Abdollahzade Fard, Amin

    2015-01-01

    Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg-1 body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes. PMID:26261706

  12. Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats.

    PubMed

    Mansouri, Esrafil; Khorsandi, Layasadat; Abdollahzade Fard, Amin

    2015-01-01

    Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg(-1) body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes.

  13. Foreign body response to subcutaneous implants in diabetic rats.

    PubMed

    Socarrás, Teresa Oviedo; Vasconcelos, Anilton C; Campos, Paula P; Pereira, Nubia B; Souza, Jessica P C; Andrade, Silvia P

    2014-01-01

    Implantation of synthetic matrices and biomedical devices in diabetic individuals has become a common procedure to repair and/or replace biological tissues. However, an adverse foreign body reaction that invariably occurs adjacent to implant devices impairing their function is poorly characterized in the diabetic environment. We investigated the influence of this condition on the abnormal tissue healing response in implants placed subcutaneously in normoglycemic and streptozotocin-induced diabetes in rats. In polyether-polyurethane sponge discs removed 10 days after implantation, the components of the fibrovascular tissue (angiogenesis, inflammation, fibrogenesis, and apoptosis) were assessed. Intra-implant levels of hemoglobin and vascular endothelial growth factor were not different after diabetes when compared with normoglycemic counterparts. However, there were a lower number of vessels in the fibrovascular tissue from diabetic rats when compared with vessel numbers in implants from non-diabetic animals. Overall, the inflammatory parameters (neutrophil accumulation--myeloperoxidase activity, tumor necrosis factor alpha, and monocyte chemotactic protein-1 levels and mast cell counting) increased in subcutaneous implants after diabetes induction. However, macrophage activation (N-acetyl-β-D-glucosaminidase activity) was lower in implants from diabetic rats when compared with those from normoglycemic animals. All fibrogenic markers (transforming growth factor beta 1 levels, collagen deposition, fibrous capsule thickness, and foreign body giant cells) decreased after diabetes, whereas apoptosis (TUNEL) increased. Our results showing that hyperglycemia down regulates the main features of the foreign body reaction induced by subcutaneous implants in rats may be relevant in understanding biomaterial integration and performance in diabetes.

  14. Insulin treatment normalizes retinal neuroinflammation but not markers of synapse loss in diabetic rats.

    PubMed

    Masser, Dustin R; VanGuilder Starkey, Heather D; Bixler, Georgina V; Dunton, Wendy; Bronson, Sarah K; Freeman, Willard M

    2014-08-01

    Diabetic retinopathy is one of the leading causes of blindness in developed countries, and a majority of patients with type I and type II diabetes will develop some degree of vision loss despite blood glucose control regimens. The effects of different insulin therapy regimens on early metabolic, inflammatory and neuronal retinal disease processes such as retinal neuroinflammation and synapse loss have not been extensively investigated. This study compared 3 months non-diabetic and streptozotocin (STZ)-induced diabetic Sprague Dawley rats. Diabetic rats received either no insulin treatment, systemic insulin treatment beginning after 1 week uncontrolled diabetes (early intervention, 11 weeks on insulin), or after 1.5 months uncontrolled diabetes (late intervention, 6 weeks on insulin). Changes in both whole animal metabolic and retinal inflammatory markers were prevented by early initiation of insulin treatment. These metabolic and inflammatory changes were also normalized by the later insulin intervention. Insulin treatment begun 1 week after diabetes induction ameliorated loss of retinal synapse markers. Synapse markers and presumably synapse numbers were equivalent in uncontrolled diabetes and when insulin treatment began at 1.5 months of diabetes. These findings are in agreement with previous demonstrations that retinal synapses are lost within 1 month of uncontrolled diabetes and suggest that synapses are not regained with glycemic control and restoration of insulin signaling. However, increased expression of metabolic and inflammatory markers associated with diabetes was reversed in both groups of insulin treatment. This study also emphasizes the need for insulin treatment groups in diabetic retinopathy studies to provide a more faithful modeling of the human condition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Role of Nitric Oxide in the Pathogenesis of Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Choi, Ki Chul; Lee, Seong Cheol; Kim, Soo Wan; Kim, Nam Ho; Lee, Jong-Un; Kang, Young Joon

    1999-01-01

    Objectives Several reports suggest that enhanced generation or actions of nitric oxide (NO) have been implicated in the pathogenesis of glomerular hyperfiltration and hyperperfusion that occurs in early diabetes. However, the precise role of altered NO generation in the pathogenesis of diabetic nephropathy is unclear. The present study was aimed at investigating the role of nitric oxide in the pathogenesis of glomerular hyperfiltration and hyperperfusion in streptozotocin-induced diabetic rats. Methods To evaluate the role of NO in diabetic hyperfiltration, we measured plasma and urine concentrations of NO2−/NO3−, stable metabolic products of NO and protein expressions of three isoforms of nitric oxide synthase (NOS) in streptozotocin-induced diabetic rats. We also investigated renal hemodynamic changes, such as glomerular filtration rate (GFR) and renal plasma flow (RPF), in responses to acute and chronic administration of NO synthesis inhibitor, nitro-L-arginine methyl ester (L-NAME), in diabetic and control rats. Results Diabetic rats exhibited significantly elevated plasma and urinary NO2−/NO3− levels at 28 days after streptozotocin injection, and total excretion of NO2−/NO3− was approximately five-fold higher in diabetic rats than controls. Insulin and L-NAME treatment prevented the increases in plasma and urinary NO2−/NO3− concentrations in diabetic rats, respectively. The three isoforms of NOS (bNOS, iNOS, and ecNOS) were all increased in the renal cortex, whereas they remained unaltered in the renal medulla at day 28. GFR and RPF were significantly elevated in diabetic rats, and acute and chronic inhibition of NO synthesis by L-NAME attenuated the renal hemodynamic changes (increases in GFR and RPF) in diabetic rats, respectively. Conclusions NO synthesis was increased due to enhanced NOS expression in diabetic rats, and chronic NO blockade attenuated renal hyperfiltration and hyperperfusion in diabetic rats. In addition, diabetic rats

  16. Development of diabetes-induced acidosis in the rat retina.

    PubMed

    Dmitriev, Andrey V; Henderson, Desmond; Linsenmeier, Robert A

    2016-08-01

    We hypothesized that the retina of diabetic animals would be unusually acidic due to increased glycolytic metabolism. Acidosis in tumors and isolated retina has been shown to lead to increased VEGF. To test the hypothesis we have measured the transretinal distribution of extracellular H(+) concentration (H(+)-profiles) in retinae of control and diabetic dark-adapted intact Long-Evans rats with ion-selective electrodes. Diabetes was induced by intraperitoneal injection of streptozotocin. Intact rat retinae are normally more acidic than blood with a peak of [H(+)]o in the outer nuclear layer (ONL) that averages 30 nM higher than H(+) in the choroid. Profiles in diabetic animals were similar in shape, but diabetic retinae began to be considerably more acidic after 5 weeks of diabetes. In retinae of 1-3 month diabetics the difference between the ONL and choroid was almost twice as great as in controls. At later times, up to 6 months, some diabetics still demonstrated abnormally high levels of [H(+)]o, but others were even less acidic than controls, so that the average level of acidosis was not different. Greater variability in H(+)-profiles (both between animals and between profiles recorded in one animal) distinguished the diabetic retinae from controls. Within animals, this variability was not random, but exhibited regions of higher and lower H(+). We conclude that retinal acidosis begins to develop at an early stage of diabetes (1-3 months) in rats. However, it does not progress, and the acidity of diabetic rat retina was diminished at later stages (3-6 months). Also the diabetes-induced acidosis has a strongly expressed local character. As result, the diabetic retinas show much wider variability in [H(+)] distribution than controls. pH influences metabolic and neural processes, and these results suggest that local acidosis could play a role in the pathogenesis of diabetic retinopathy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Hydrogen sulfide accelerates wound healing in diabetic rats

    PubMed Central

    Wang, Guoguang; Li, Wei; Chen, Qingying; Jiang, Yuxin; Lu, Xiaohua; Zhao, Xue

    2015-01-01

    Aim: The aim of this study was to explore the role of hydrogen sulfide on wound healing in diabetic rats. Methods: Experimental diabetes in rats was induced by intraperitoneal injection of streptozotocin (STZ) (in 0.1 mol/L citrate buffer, Ph 4.5) at dose of 70 mg/kg. Diabetic and age-matched non-diabetic rats were randomly assigned to three groups: untreated diabetic controls (UDC), treated diabetic administrations (TDA), and non-diabetic controls (NDC). Wound Healing Model was prepared by making a round incision (2.0 cm in diameter) in full thickness. Rats from TDA receive 2% sodium bisulfide ointment on wound, and animals from UDC and NDC receive control cream. After treatment of 21 days with sodium bisulfide, blood samples were collected for determination of vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), antioxidant effects. Granulation tissues from the wound were processed for histological examination and analysis of western blot. Results: The study indicated a significant increase in levels of VEGF and ICAM-1 and a decline in activity of coagulation in diabetic rats treated with sodium bisulfide. Sodium bisulfide treatment raised the activity of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein expression, and decreased tumor necrosis factor α (TNF-α) protein expression in diabetic rats. Conclusions: The findings in present study suggested that hydrogen sulfide accelerates the wound healing in rats with diabetes. The beneficial effect of H2S may be associated with formation of granulation, anti-inflammation, antioxidant, and the increased level of vascular endothelial growth factor (VEGF). PMID:26191204

  18. Steps of glucocorticoid action in normal and diabetic rat placenta.

    PubMed

    Heller, C L; Weisenberg, L S; Ortí, E; De Nicola, A F

    1988-07-01

    This investigation examined the effects of Streptozotocin diabetes in pregnancy on several parameters of glucocorticoid action in the rat placenta. Pregnant diabetic rats showed reduced body weight, increased adrenal weight and serum corticosterone concentrations. Glucocorticoid receptors in placental cytosol of labyrinthine zone, measured in the absence of MoO4Na2 were similar in control and diabetic rats, but after addition of MoO4Na2 receptor number were moderately, but significantly reduced in diabetic placentas (P less than 0.01). No changes in affinity were detected in saturation analysis. Furthermore, transformation of the receptor assessed by its capacity for binding to DNA-cellulose, was enhanced in diabetic animals, suggesting increased efficiency of the receptor-bound hormone. Since the function of the glucocorticoid receptor of rat placenta may be the inhibition of local progesterone production (Heller and De Nicola, J. steroid Biochem. 19 (1983) 1339-1343), we determined progesterone synthesis in vitro and found that diabetic placentas synthesized significantly less progesterone than control tissue (P less than 0.05). Lastly, we found that the metabolism of corticosterone to 11-dehydrocorticosterone, while declining in control placentas as pregnancy advanced, it was sustained in diabetic pregnancy. It is suggested that diabetic rat placentas showed increased activity towards the glucocorticoid receptor, resulting in reduction in progesterone synthesis and sustained catabolism of corticosterone. The latter may possibly constitute a compensatory mechanism to protect the fetal compartment from high levels of maternal glucocorticoids.

  19. Chronic cobalt treatment decreases hyperglycemia in streptozotocin-diabetic rats.

    PubMed

    Vasudevan, Harish; McNeill, John H

    2007-04-01

    Diabetes is a metabolic disorder characterized by elevated blood glucose levels. Although conventional treatments such as insulin and other drugs reduce blood glucose, there is still a therapeutic need for effective orally administered drugs. Trace elements like vanadium and tungstate have been successfully demonstrated to reduce blood glucose in experimental diabetes with minimal chronic complications. We investigated the anti-hyperglycemic effects of cobalt in streptozotocin-diabetic rats. Normal and diabetic rats were provided with drinking water containing 3.5 mM cobalt chloride for three weeks followed by 4 mM for four weeks. Body weights and fluid consumption were monitored on a daily basis, while food intake was recorded twice every week. Prior to termination, an oral glucose tolerance test was performed on the animals. Diabetic rats lost significant body weight (357 +/- 2 gm) compared to controls (482 +/- 3 gm). Body weight was further reduced by cobalt treatment (290 +/- 2 gm). Although it was difficult to establish a dosing regimen without weight loss, food and fluid consumption in cobalt-treated diabetic rats improved significantly compared to untreated diabetics. Plasma glucose levels were significantly reduced with reference to diabetic controls (29.3 +/- 0.9 mM) by the fourth week to a lower but still hyperglycemic level (13.6 +/- 3.4 mM). Cobalt-treated diabetic rats demonstrated an enhanced ability to clear a glucose load compared to untreated diabetics. Cobalt treatment neither affected the feeding and drinking patterns nor plasma glucose in normoglycemic animals although body weights decreased compared to untreated controls. We conclude that chronic cobalt treatment decreases plasma glucose levels in STZ-diabetic rats and improves tolerance to glucose.

  20. Oxymatrine attenuates diabetes-associated cognitive deficits in rats

    PubMed Central

    Wang, Suo-bin; Jia, Jian-ping

    2014-01-01

    Aim: Oxymatrine (OMT) is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait (the Chinese herb Kushen) and exhibits diverse pharmacological actions. In this work we investigated the effects of OMT on diabetes-associated cognitive decline (DACD) in a rat model of diabetes and explored the mechanisms of action. Methods: Male Wistar rats were injected with streptozotocin (65 mg/kg, ip) once to induce diabetes. The rats were then treated with vehicle or OMT (60 or 120 mg/kg per day, ip) for 7 weeks. Memory function was assessed using Morris water maze test. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), NF-κB p65 unit, TNF-α, IL-1β and caspase-3 in the cerebral cortex and hippocampus were quantified. Results: The diabetic rats exhibited markedly reduced body weight and increased plasma glucose level. The memory function of the rats assessed using Morris water maze test showed significant reduction in the percentage of time spent in the target quadrant and the number of times crossing the platform, coupled with markedly prolongation of escape latency and mean path length. Moreover, the rats showed oxidative stress (significantly increased MDA, decreased SOD and reduced GSH levels), as well as significant increases of NF-κB p65 unit, TNF-α, IL-1β and caspase-3 levels in the cerebral cortex and hippocampus. Chronic treatment with OMT dose-dependently reversed these behavioral, biochemical and molecular changes in the diabetic rats. However, the swimming speed had no significant difference among the control, diabetic and OMT-treated diabetic rats. Conclusion: Chronic treatment with OMT alleviates diabetes-associated cognitive decline in rats, which is associated with oxidative stress, inflammation and apoptotic cascades. PMID:24442148

  1. Chromium yeast supplementation improves fasting plasma glucose and LDL-cholesterol in streptozotocin-induced diabetic rats.

    PubMed

    Lai, Ming-Hoang; Chen, Ya-Yen; Cheng, Hsing-Hsien

    2006-11-01

    Chromium yeast supplementation has been studied for its ability to improve carbohydrate and lipid abnormalities. There have been some earlier literature-reported studies involving chromium supplementation amongst patients suffering diabetes, but the results would appear to be somewhat varied. Forty male Wistar rats (ten weeks old, 300 g in average body mass) were divided into one of four groups, namely (i) controls; (ii) controls treated with chromium yeast; (iii) diabetic controls; and (iv) diabetic rats treated with chromium yeast. In the present investigation, the effect of a four-week oral administration of chromium yeast (600 microg of Cr/kg body mass/day, by gavage) upon the glucose and lipid metabolism in streptozotocin (STZ)-induced diabetic rats was assessed. Supplemental Cr yeast decreased the fasting blood glucose amongst the STZ-diabetic rats. No significant difference was observed in plasma fructosamine levels of rats treated with chromium yeast compared to control rats. Supplemental Cr yeast did decrease the plasma low-density lipoprotein (LDL)-cholesterol level for the STZ-diabetic rats as compared to controls. We noted no significant effect of chromium supplementation upon plasma high-density lipoprotein (HDL)-cholesterol or triglycerides compared to controls. Treatment with chromium yeast significantly increased the blood and urine chromium levels for both the diabetic and normal rats compared to respective control groups. The results of these studies suggest that Cr yeast decreased the fasting blood glucose and LDL-cholesterol levels in STZ-induced diabetic rats. This raises the possibility that Cr yeast supplementation can be considered to improve carbohydrate and lipid metabolism amongst human patients featuring type 2 diabetes mellitus.

  2. Embelin accelerates cutaneous wound healing in diabetic rats.

    PubMed

    Deshmukh, Pradeep T; Gupta, Vipin B

    2013-01-01

    This study reports the effect of embelin (1) on cutaneous wound in streptozotocin (STZ)-induced diabetic rats. The effect was studied using excision, incision, and dead space models. In diabetic rats, topical application of embelin 5% (w/w) ointment showed a significant increase in wound contraction and better epithelialization, thereby facilitating the healing. Embelin was also active by the oral route (25 and 50 mg/kg) in the incision and dead space wound models. In incision wound model, wound granulation tissues were removed on 8th post-wounding day, and the hydroxyproline, hexosamine, total protein, and DNA contents were determined. In STZ diabetic rats, topical and oral applications of embelin showed an increase in hydroxyproline, hexosamine, total protein, and DNA contents. It also showed a significant increase in wound breaking strength. Embelin significantly increased granuloma tissue weight and breaking strength in dead space model. These results indicated that embelin accelerated wound healing in diabetic rat.

  3. The Effects of Creatine Monohydrate on Permeability of Coronary Artery Endothelium and Level of Blood Lipoprotein in Diabetic Rats.

    PubMed

    Rahmani, Asghar; Asadollahi, Khairollah; Soleimannejad, Kourosh; Khalighi, Zahra; Mohsenzadeh, Yosouf; Hemati, Ruhollah; Moradkhani, Atefeh; Abangah, Ghobad

    2016-09-01

    Creatine monohydrate has beneficial effects on serum glucose. This study aimed to investigate the effects of creatine on serum biochemical markers and permeability of coronary arteries among diabetic rats. 32 Wistar rats, which weighed 150-200 grams were randomly divided into 4 groups including: group I, control; group II, creatine monohydrate; group III, diabetic rats; and group IV, diabetic rats + creatine. Creatine monohydrate was applied by 400 mg/kg/daily for 5 months. Animals' weights and blood samples were taken before and after the study. Endothelial permeability rate was measured by Evans Blue method. Data were analysed by SPSS 16. At the end of fifth month, rats' weights in diabetic group under treatment with creatine, compared to those without, increased significantly (p<0.0001). Also, the serum levels of triglyceride (TG), cholesterol, glucose and low density lipoprotein (LDL)- cholesterol decreased significantly among those under treatment with creatine (p<0.05), but high density lipoprotein (HDL)- cholesterol increased significantly (p<0.002). Permeability rate of coronary arteries was reduced significantly in the diabetic group treated by creatine compared to untreated groups, closed to the intact group (p<0.001). Results of this study showed that creatine monohydrate caused an improvement of serum biochemical markers associated with diabetes and reduced the permeability rate of coronary arteries among diabetic rats. © 2016 by the Association of Clinical Scientists, Inc.

  4. Compromised Wound Healing in Ischemic Type 2 Diabetic Rats

    PubMed Central

    Yu, Tianyi; Chang, Qingxuan; Wang, Di; Gao, Min; Zhang, Xiong; Liu, Yan

    2016-01-01

    Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8weeks high fat diet (HFD) feeding regimen followed by multiple injections of streptozotocin (STZ) at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds. PMID:27028201

  5. Compromised Wound Healing in Ischemic Type 2 Diabetic Rats.

    PubMed

    Yang, Peilang; Pei, Qing; Yu, Tianyi; Chang, Qingxuan; Wang, Di; Gao, Min; Zhang, Xiong; Liu, Yan

    2016-01-01

    Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8 weeks high fat diet (HFD) feeding regimen followed by multiple injections of streptozotocin (STZ) at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds.

  6. Neuroprotective effects of quercetin in diabetic rat retina.

    PubMed

    Ola, Mohammad S; Ahmed, M M; Shams, Shakeeb; Al-Rejaie, Salim S

    2017-09-01

    Diabetic retinopathy (DR) is a severe complication of diabetes and the leading cause of blindness among working adults worldwide. DR is being widely recognized as a neurodegenerative disease of the retina, since, retinal neurons are damaged soon after diabetes onset. Diabetes-induced oxidative stress is considered as central factor that dysregulates neurotrophic factors and activates apoptosis, thereby damages neurons in the diabetic retina. Flavonoids being a powerful antioxidant have been considered to protect neurons in diabetic retina. The purpose of this study was to analyze the beneficial effects of flavonoid, quercetin to protect neurons in the diabetic rat retina. We quantitated the expression levels of BDNF, NGF, TrkB, synaptophysin, Akt, Bcl-2, cytochrome c and caspase-3 using Western blotting techniques in the diabetic retina with and without quercetin treatments and compared with non-diabetic rats. In addition, we employed ELISA techniques to determine the level of BDNF. Caspase-3 activity and the level of glutathione were analyzed by biochemical methods. Our results indicate that quercetin treatment to diabetic rats caused a significant increase in the level of neurotrophic factors and inhibited the level of cytochrome c and caspase-3 activity in the diabetic retina. Furthermore, the level of an anti-apoptotic protein Bcl-2 was augmented in quercetin treated diabetic retina. Thus, quercetin, may protect the neuronal damage in diabetic retina by ameliorating the levels of neurotrophic factors and also by inhibiting the apoptosis of neurons. Therefore, this study suggests that quercetin can be a suitable therapeutic agent to prevent neurodegeneration in diabetic retinopathy.

  7. Remodeling intestinal flora with sleeve gastrectomy in diabetic rats.

    PubMed

    Huang, Xiaofei; Weng, Pan; Zhang, Huixin; Lu, Yingli

    2014-01-01

    As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them underwent sham operation. Meanwhile 10 male normal rats underwent sleeve gastrectomy as control. The animals' weight and FBG had been measured. The composition changes of intestinal flora were detected by 16S rDNA sequence analysis. In diabetic rats, weight and fasting blood glucose decreased significantly after sleeve gastrectomy. However, there was no significant change for weight and blood glucose in normal rats after operation. The intestinal flora of diabetic rats reduced in the proportion of Firmicutes and increased in the proportion of Bacteroidetes after sleeve gastrectomy. The change of dominant microorganisms in intestinal flora might play an important role in the glucose metabolism.

  8. Remodeling Intestinal Flora with Sleeve Gastrectomy in Diabetic Rats

    PubMed Central

    Huang, Xiaofei; Weng, Pan; Zhang, Huixin; Lu, Yingli

    2014-01-01

    Objective. As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats. Methods. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them underwent sham operation. Meanwhile 10 male normal rats underwent sleeve gastrectomy as control. The animals' weight and FBG had been measured. The composition changes of intestinal flora were detected by 16S rDNA sequence analysis. Results. In diabetic rats, weight and fasting blood glucose decreased significantly after sleeve gastrectomy. However, there was no significant change for weight and blood glucose in normal rats after operation. The intestinal flora of diabetic rats reduced in the proportion of Firmicutes and increased in the proportion of Bacteroidetes after sleeve gastrectomy. Conclusion. The change of dominant microorganisms in intestinal flora might play an important role in the glucose metabolism. PMID:25165722

  9. Butea superba (Roxb.) improves penile erection in diabetic rats.

    PubMed

    Tocharus, C; Sooksaen, P; Shimbhu, D; Tocharus, J

    2012-05-01

    The objective of the present study was to investigate the effect of ethanolic extract of Butea superba (Roxb.) on erectile dysfunction in diabetic rats by the measurement of intracavernous pressure (ICP) and on cavernosal smooth muscle relaxation. Male Sprague-Dawley rats were induced to become diabetic by a single intravenous injection of Streptozotocin (55 mg kg(-1) body weight). The ethanolic extract at the concentration of 1, 10 and 100 mg kg(-1) BW was administered orally once a day to diabetic rats in each group for 4 weeks. Diabetic rats showed a significant decrease in both ICP and the relaxation of the cavernosal smooth muscle compared with the normal rats. The extract of B. superba significantly increased the ICP with the effective dose of 10 mg kg(-1) BW (61.00 ± 11.11 mmHg versus 39.61 ± 11.01 mmHg in the diabetic control group). Moreover, the B. superba-treated group also showed enhanced relaxation of the cavernosal smooth muscle with EC(50) of 1.17 mg ml(-1). These results suggest that the extract of B. superba enhanced penile erection in diabetic rats by increasing the ICP. This might be explained by the increased blood flow as a result of the relaxation of the cavernous smooth muscle. © 2011 Blackwell Verlag GmbH.

  10. DEVELOPMENT OF PERIRADICULAR LESIONS IN NORMAL AND DIABETIC RATS

    PubMed Central

    Armada-Dias, Luci; Breda, Jorge; Provenzano, José Claudio; Breitenbach, Marisa; Rôças, Isabela das Neves; Gahyva, Sérgio Márcio Motta; Siqueira, José Freitas

    2006-01-01

    Evidence suggests that diabetic patients are more significantly affected by problems of endodontic origin. This study sought to radiographically and histologically examine the development of periradicular inflammation in control and in diabetic rats after induction of pulpal infection. The pulps of the mandibular first molars of normal and streptozotocin-induced diabetic rats were exposed and left in contact with their oral cavities for 21 and 40 days. Afterwards, the animals were sacrificed, the mandibles were surgically removed, fixed in formalin and then radiographed in a standardized position. The radiographic images of the periradicular lesions were scanned and computerized images were evaluated for the total area of the lesions using a specific software. Representative specimens were also prepared for histopathological analysis. Radiographic analysis revealed that diabetic rats presented significantly larger periradicular lesions when compared with control rats, regardless of the experimental period (p<0.05). Histopathological examination of representative specimens revealed larger periradicular lesions and more severe inflammatory exudate in the group of diabetic rats when compared with the control group. Data from the present study indicated that diabetic rats can be more prone to develop large periradicular lesions, possibly due to reduction in the defense ability against microbial pathogens. PMID:19089060

  11. Nitric oxide dynamics and endothelial dysfunction in type II model of genetic diabetes.

    PubMed

    Bitar, Milad S; Wahid, Sabah; Mustafa, Seham; Al-Saleh, Eyad; Dhaunsi, Gursev S; Al-Mulla, Fahd

    2005-03-21

    Although diabetes is a major risk factor for vascular diseases, e.g., hypertension and atherosclerosis, mechanisms that underlie the "risky" aspects of diabetes remain obscure. The current study is intended to examine the notion that diabetic endothelial dysfunction stems from a heightened state of oxidative stress induced by an imbalance between vascular production and scavenging of reactive oxygen/nitrogen species. Goto-Kakizaki (GK) rats were used as a genetic animal model for non-obese type II diabetes. Nitric oxide (NO) bioavailability and O2- generation in aortic tissues of GK rats were assessed using the Griess reaction and a lucigenin-chemiluminescence-based technique, respectively. Organ chamber-based isometric tension studies revealed that aortas from GK rats had impaired relaxation responses to acetylcholine whereas a rightward shift in the dose-response curve was noticed in the endothelium-independent vasorelaxation exerted by the NO donor sodium nitroprusside. An enhancement in superoxide (O2-) production and a diminuation in NO bioavailability were evident in aortic tissues of GK diabetic rats. Immunoblotting and high-performance liquid chromatography (HPLC)-based techniques revealed, respectively, that the above inverse relationship between O2- and NO was associated with a marked increase in the protein expression of nitric oxide synthase (eNOS) and a decrease in the level of its cofactor tetrahydrobiopterin (BH4) in diabetic aortas. Endothelial denudation by rubbing or the addition of pharmacological inhibitors of eNOS (e.g. N(omega)-nitro-L-arginine methyl ester (L-NAME)), and NAD(P)H oxidase (e.g. diphenyleneiodonium, apocynin) strikingly reduced the diabetes-induced enhancement in vascular O2- production. Aortic contents of key markers of oxidative stress (isoprostane F2alpha III, protein-bound carbonyls, nitrosylated protein) in connection with the protein expression of superoxide generating enzyme NAD(P)H oxidase (e.g. p47phox, pg91phox), a

  12. Insulin modulates inflammatory and repair responses to elastase-induced emphysema in diabetic rats.

    PubMed

    Di Petta, Antonio; Greco, Karin V; Castro, Eveline O; Lopes, Fernanda D T Q S; Martins, Milton A; Capelozzi, Vera L; Moreira, Luiz F P; Sannomiya, Paulina

    2011-12-01

    As pulmonary emphysema and diabetes mellitus are common diseases, concomitance of both is correspondingly expected to occur frequently. To examine whether insulin influences the development of inflammation in the alveolar septa, diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., n = 37) and matching controls (n = 31) were used. Ten days after alloxan injection, diabetic and control rats were instilled with physiologic saline solution containing porcine pancreatic elastase (PPE, 0.25 IU/0.2 ml, right lung) or saline only (left lung). The following analyses were performed: (i) number of leucocytes in the bronchoalveolar lavage (BAL) fluid of the animals, 6 h after PPE/saline instillation (early time point); and (ii) mean alveolar diameter (μm) and quantification of elastic and collagen fibres (%) 50 days after PPE/saline instillation (late time point). Relative to controls, alloxan-induced diabetic rats showed a 42% reduction in the number of neutrophils in BAL fluid, a 20% increase in the mean alveolar diameter and a 33% decrease in elastic fibre density in the alveolar septa. Treatment of diabetic rats with 4 IU neutral protamine Hagedorn (NPH) insulin, 2 h before elastase instillation, restored the number of neutrophils in the BAL fluid. The mean alveolar diameter and elastic fibre content in alveolar septa matched the values observed in control rats if diabetic rats were treated with 4 IU NPH insulin 2 h before instillation followed by 2 IU/day for the next 50 days. Density of collagen fibres did not differ between the various groups. Thus, the data presented suggest that insulin modulates the inflammatory and repair responses in elastase-induced emphysema, and assures normal repair and tissue remodelling.

  13. Increased caspase-3 immunoreactivity of erythrocytes in STZ diabetic rats.

    PubMed

    Fırat, Uğur; Kaya, Savaş; Cim, Abdullah; Büyükbayram, Hüseyin; Gökalp, Osman; Dal, Mehmet Sinan; Tamer, Mehmet Numan

    2012-01-01

    Eryptosis is a term to define apoptosis of erythrocytes. Oxidative stress and hyperglycemia, both of which exist in the diabetic intravascular environment, can trigger eryptosis of erythrocytes. In this experimental study, it is presented that the majority of erythrocytes shows caspase-3 immunoreactivity in streptozocin- (STZ)-induced diabetic rats. Besides that, caspase-3 positive erythrocytes are aggregated and attached to vascular endothelium. In conclusion, these results may start a debate that eryptosis could have a role in the diabetic complications.

  14. Effect of dragon fruit extract on oxidative stress and aortic stiffness in streptozotocin-induced diabetes in rats

    PubMed Central

    Anand Swarup, Kolla R. L.; Sattar, Munavvar A.; Abdullah, Nor A.; Abdulla, Mohammed H.; Salman, Ibrahim M.; Rathore, Hassaan A.; Johns, Edward J.

    2010-01-01

    Cardiovascular complications are consistently observed in diabetic patients across all age groups. The objective of the present study was to investigate the effect of aqueous extract of the fruit pulp of Hylocereus undatus (DFE) on aortic stiffness and oxidative stress in streptozotocin (STZ)-induced diabetes in rats. Twenty-four male, Sprague-Dawley rats were randomized into four groups: I (control), II (diabetic), III (DFE, 250 mg/kg) and IV (DFE 500 mg/kg). Diabetes was induced in groups II, III and IV by intraperitoneal (i.p.) injection of STZ (40 mg/kg). After confirmation of diabetes, group III and IV received DFE for 5 weeks. Pulse wave velocity (PWV) was used as a marker of aortic stiffness and was determined at the end of 5 weeks. DFE significantly decreased (P < 0.05) the fasting blood glucose levels in diabetic rats, but not to normal levels. Systolic blood pressure, pulse pressure and PWV were significantly increased (P < 0.05) in diabetic rats at the end of 5 weeks in comparison with control group. DFE treatment significantly decreased (P < 0.05) these elevations. Oxidative damage was observed in group II after 5 weeks. Plasma malondialdehyde levels significantly decreased (P < 0.05), while superoxide dismutase and total antioxidant capacity significantly increased (P < 0.05) with DFE treatment in comparison with group II. These data demonstrate that DFE treatment was effective in controlling oxidative damage and decreasing the aortic stiffness measured by PWV in STZ-induced diabetes in rats. PMID:21808536

  15. Effect of dragon fruit extract on oxidative stress and aortic stiffness in streptozotocin-induced diabetes in rats.

    PubMed

    Anand Swarup, Kolla R L; Sattar, Munavvar A; Abdullah, Nor A; Abdulla, Mohammed H; Salman, Ibrahim M; Rathore, Hassaan A; Johns, Edward J

    2010-01-01

    Cardiovascular complications are consistently observed in diabetic patients across all age groups. The objective of the present study was to investigate the effect of aqueous extract of the fruit pulp of Hylocereus undatus (DFE) on aortic stiffness and oxidative stress in streptozotocin (STZ)-induced diabetes in rats. Twenty-four male, Sprague-Dawley rats were randomized into four groups: I (control), II (diabetic), III (DFE, 250 mg/kg) and IV (DFE 500 mg/kg). Diabetes was induced in groups II, III and IV by intraperitoneal (i.p.) injection of STZ (40 mg/kg). After confirmation of diabetes, group III and IV received DFE for 5 weeks. Pulse wave velocity (PWV) was used as a marker of aortic stiffness and was determined at the end of 5 weeks. DFE significantly decreased (P < 0.05) the fasting blood glucose levels in diabetic rats, but not to normal levels. Systolic blood pressure, pulse pressure and PWV were significantly increased (P < 0.05) in diabetic rats at the end of 5 weeks in comparison with control group. DFE treatment significantly decreased (P < 0.05) these elevations. Oxidative damage was observed in group II after 5 weeks. Plasma malondialdehyde levels significantly decreased (P < 0.05), while superoxide dismutase and total antioxidant capacity significantly increased (P < 0.05) with DFE treatment in comparison with group II. These data demonstrate that DFE treatment was effective in controlling oxidative damage and decreasing the aortic stiffness measured by PWV in STZ-induced diabetes in rats.

  16. Skin changes in streptozotocin-induced diabetic rats.

    PubMed

    Andrade, Thiago Antônio Moretti; Masson-Meyers, Daniela Santos; Caetano, Guilherme Ferreira; Terra, Vânia Aparecida; Ovidio, Paula Payão; Jordão-Júnior, Alceu Afonso; Frade, Marco Andrey Cipriani

    2017-09-02

    Diabetes can cause serious health complications, which can affect every organ of the body, including the skin. The molecular etiology has not yet been clarified for all diabetic skin conditions. Thus, this study aimed to investigate the changes of diabetes in skin compared to non-diabetic skin in rats. Fifteen days after establishing the diabetic status, skin samples from the dorsum-cervical region were harvested for subsequent analysis of alterations caused by diabetes. Our results demonstrate that diabetes stimulated higher inflammation and oxidative stress in skin, but antioxidant defense levels were lower compared to the non-diabetic group (p < 0.05). This could have been related to a decreased number of blood vessels and low expression of VEGF, eNOS and TGF-β1. Finally, insulin signaling proteins IRS, Akt, Shc and ERK showed a low expression in the diabetic group. Thus, our study shows that the pathology of diabetes induced immunohistopathological and biochemical skin changes compared to non-diabetic skin in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin.

    PubMed

    Wu, Duo; Wen, Wei; Qi, Chun-Li; Zhao, Ru-Xia; Lü, Jun-Hua; Zhong, Chun-Yan; Chen, Yi-Yu

    2012-06-15

    Berberine (BBR) is one of the main constituents in Rhizoma coptidis and it has widely been used for the treatment of diabetic nephropathy. The aims of the study were to investigate the effects and mechanism of action of berberine on renal damage in diabetic rats. Diabetes and hyperglycaemia were induced in rats by a high-fat diet and intraperitoneal injection of 40 mg/kg streptozotocin (STZ). Rats were randomly divided into 5 groups, such as i) control rats, ii) untreated diabetic rats iii) 250 mg/kg metformin-treated, iv and v) 100 and 200 mg/kg berberine-treated diabetic rats and treated separately for 8 weeks. The fasting blood glucose, insulin, total cholesterol, triglyceride, glycosylated hemoglobin were measured in rats. Kidneys were isolated at the end of the treatment for histology, Western blot analysis and estimation of malonaldehyde (MDA), superoxide dismutase (SOD) and renal advanced glycation endproducts (AGEs). The results revealed that berberine significantly decreased fasting blood glucose, insulin levels, total cholesterol, triglyceride levels, urinary protein excretion, serum creatinine (Scr) and blood urea nitrogen (BUN) in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following treatment with berberine. In addition, the protein expressions of nephrin and podocin were significantly increased. It seems likely that in rats berberine exerts an ameliorative effect on renal damage in diabetes induced by high-fat diet and streptozotocin. The possible mechanisms for the renoprotective effects of berberine may be related to inhibition of glycosylation and improvement of antioxidation that in turn upregulate the expressions of renal nephrin and podocin.

  18. Cardioprotective effect of pioglitazone in diabetic and non-diabetic rats subjected to acute myocardial infarction involves suppression of AGE-RAGE axis and inhibition of apoptosis.

    PubMed

    Khodeer, Dina M; Zaitone, Sawsan A; Farag, Noha E; Moustafa, Yasser M

    2016-05-01

    Insulin resistance increases risk of cardiovascular diseases. This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery. Male rats were divided into 2 experiments: experiment I and II (non-diabetic and diabetic rats) were assigned as saline, MI (isoproterenol, 85 mg/kg, daily), and MI+pioglitazone (5, 10, and 20 mg/kg). Injection of isoproterenol in diabetic rats produced greater ECG disturbances compared to non-diabetic rats. Treatment with pioglitazone (5 mg/kg) reduced the infarct size and improved some ECG findings. Pioglitazone (10 mg/kg) enhanced ECG findings, improved the histopathological picture and downregulated apoptosis in cardiac tissues. Whereas the higher dose of pioglitazone (20 mg/kg) did not improve most of the measured parameters but rather worsened some of them, such as proapoptotic markers. Importantly, a positive correlation was found between serum AGEs and cardiac AGE receptors (RAGEs) versus caspase 3 expression in the two experiments. Therefore, the current effect of pioglitazone was, at least in part, mediated through downregulation of AGE-RAGE axis and inhibition of apoptosis. Consequently, these data suggest that pioglitazone, at optimized doses, may have utility in protection from acute MI.

  19. Glomerular filtration rate determinations in conscious type II diabetic mice

    PubMed Central

    Bivona, Benjamin J.; Park, Sungmi

    2011-01-01

    Diabetic nephropathy is a major cause of end-stage renal disease worldwide. The current studies were performed to determine the later stages of the progression of renal disease in type II diabetic mice (BKS; db/db). Methodology was developed for determining glomerular filtration rate (GFR) in conscious, chronically instrumented mice using continuous intravenous infusion of FITC-labeled inulin to achieve a steady-state plasma inulin concentration. Obese diabetic mice exhibited increased GFR compared with control mice. GFR averaged 0.313 ± 0.018 and 0.278 ± 0.007 ml/min in 18-wk-old obese diabetic (n = 11) and control (n = 13) mice, respectively (P < 0.05). In 28-wk-old obese diabetic (n = 10) and control (n = 15) mice, GFR averaged 0.348 ± 0.030 and 0.279 ± 0.009 ml/min, respectively (P < 0.05). GFR expressed per gram BW was significantly reduced in 18- and 28-wk-old obese diabetic compared with control mice (5.9 ± 0.3 vs. 9.0 ± 0.3; 6.6 ± 0.6 vs. 7.8 ± 0.3 μl·min−1·g body wt−1), respectively (P < 0.05). However, older nonobese type II diabetic mice had significantly reduced GFR (0.179 ± 0.023 ml/min; n = 6) and elevated urinary albumin excretion (811 ± 127 μg/day) compared with obese diabetic and control mice (514 ± 54, 171 ± 18 μg/day), which are consistent with the advanced stages of renal disease. These studies suggest that hyperfiltration contributes to the progression of renal disease in type II diabetic mice. PMID:21147841

  20. Neuroprotective effects of octreotide on diabetic neuropathy in rats.

    PubMed

    Solmaz, Volkan; Çınar, Bilge Piri; Yiğittürk, Gürkan; Özlece, Hatice Köse; Avni Eroglu, Hüseyin; Tekatas, Aslan; Erbaş, Oytun; Taşkıran, Dilek

    2017-02-26

    The purpose of the present study is to investigate the possible healing effects of octreotide (OCT) on motor performance, electrophysiological and histopathological findings of diabetic neuropathy in a rat model of diabetes mellitus (DM). To induce diabetes, rats were administered a single dose (60mg/kg) of streptozotocin (STZ). Diabetic rats were treated either with saline (1ml/kg/day, n=7) or OCT (0.1mg/kg/day, n=7) for four weeks. Seven rats served as control group and received no treatment. At the end of the study, electromyography (EMG), gross motor function (inclined plate test), general histology and the perineural thickness of sciatic nerve were evaluated. At the end of study, weight loss was significantly lower in OCT treated rats than that of saline treated ones (p<0.001). Electrophysiologically, compound muscle action potential (CMAP) amplitudes of the saline treated DM group were significantly reduced than those of controls (p<0.0001). Also, distal latency and CMAP durations were significantly prolonged in saline treated DM group (p<0.05) compared to control. However, treatment of diabetic rats with OCT significantly counteracted these alterations in EMG. Furthermore, OCT significantly improved the motor performance scores in diabetic rats (p<0.05). Histomorphometric assessment of the sciatic nerve demonstrated a significant reduction in perineural thickness in OCT treated group compared to saline group. In conclusion, OCT possesses beneficial effects against STZ-induced diabetic neuropathy, which promisingly support the use of OCT as a neuroprotective agent in patients with diabetic neuropathy.

  1. Topical embryonic stem cells enhance wound healing in diabetic rats.

    PubMed

    Lee, Keun-Bae; Choi, Jin; Cho, Seong-Beom; Chung, Jae-Yoon; Moon, Eun-Sun; Kim, Nack-Sung; Han, Ho-Jae

    2011-10-01

    The effects of embryonic stem cells (ESCs) on diabetic wound healing were investigated using an excisional skin wound model in 110 diabetes-induced rats. We transplanted a clonal population of ESCs (5 × 10(6)) by topical injection into full thickness skin wounds. Four study groups were used; nondiabetic rats as a control, non-insulin controlled diabetic rats not treated with ESCs, insulin controlled diabetic rats not treated with ESCs, and insulin controlled diabetic rats treated with ESCs. Five rats in each experimental group were sacrificed on days 1, 5, 10, 15, and 20 after wounding. Wounds images were acquired daily and wound sizes were calculated. We measured the mRNA levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), and fibronectin levels in extracellular matrix, and assessed wound healing by assessing histological parameters of epidermal regeneration, granulation tissue thickness, and angiogenesis. In the ESC-treated group, wound sizes were significantly smaller than in the insulin controlled diabetic group not treated with ESCs on days 5 and 10 (p < 0.05), and EGF and VEGF levels were markedly higher on days 5 and 10, fibronectin levels on day 5 after injection. All histological scores in the ESC-treated group were significantly higher than those of the insulin controlled diabetic group on day 5 (p < 0.05). Our results shows that topical ESCs enhance diabetic wound healing during the early stage, and suggest that ESCs transplantation offers a novel therapeutic modality for the treatment of diabetic wounds.

  2. Hepcidin and iron metabolism in non-diabetic obese and type 2 diabetic rats.

    PubMed

    Chen, Yue; Yin, Hui-qing; Liu, Hao-ling; Xiu, Lei; Peng, Xiao-yu

    2015-12-01

    The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats were divided into 3 groups: control group, non-diabetic obese group and type 2 diabetic group (n=20 each). The rats were evaluated physiologically and biochemically. The hepatic histopathological changes were observed using haematoxylin and eosin (HE) staining. The mRNA expression patterns of hepcidin, interleukin-6 (IL-6), hypoxia-inducible factor (HIF) and ferroportin (Fpn) in the rat liver in control group, non-diabetic obese group and type 2 diabetic group were analyzed by real-time RT-PCR. The protein expression patterns of hepcidin in liver of each group were further analyzed by immunohistochemistry and Western blotting. As compared with control group, the ferritin in non-diabetic obese group and type 2 diabetic group was increased significantly (P<0.001). However, there was no significant difference in soluble transferring receptor (sTfR):ferritin ratio among the three groups (P>0.05). The real-time RT-PCR, immunohistochemistry and Western blotting results all revealed that the expression levels of hepcidin in non-diabetic obese group and type 2 diabetic group were elevated significantly as compared with those in control group (P<0.001). The expression levels of hepcidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant difference (P>0.05). However, the protein expression levels of hepcidin in type 2 diabetic group were significantly higher than those in non-diabetic obese group (P<0.05). Compared to control group, the expression levels of IL-6 mRNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels of Fpn mRNA decreased (P<0.05). However, the expression levels of HIF mRNA had no significant difference among three groups. It is suggested that iron metabolism is

  3. Duration effect of Acacia nilotica leaves extract and glibenclamide as hypolipidaemic and hypoglycaemic activity in alloxan induced diabetic rats.

    PubMed

    Asad, Munazza; Munir, Tahir Ahmad; Farid, Sadaf; Aslam, Muhammad; Shah, Syed Shoaib

    2015-12-01

    To compare the duration and effects of aqueous methanol Acacia-nilotica leaves extract and glibenclamide as hypoglycaemic and hypolipidaemic activity in diabetic rats. The experimental study was conducted at Shifa International Hospital in collaboration with National Institute of Health, Islamabad, from September 2010 to August 2011.Male Sprague Dawley albino rats were taken and divided into 8 equal groups. Groups I and II were the normal and diabetic control rats. Diabetes mellitus was induced in group II to VIII by administering 110 mg/kg body weight alloxanand at day 4, fasting blood glucose level of >200 mg/dl confirmed diabetes. Acacia-nilotica leaves extract was given to group III, IV and V and glibenclamide to group VI to VIII for a period of 1-3 weeks. Blood samples were analysed for lipid profile using enzymatic calorimetric method and serum insulin by enzyme-linked immunosorbent assay on days 0, 7, 14, and 21. There were 64 rats in the study, with 8(12.5%) in each group. Statistically significant decreases in fasting blood glucose, total cholesterol, triglyceride, phospholipids, low density lipoprotein, very low density lipoprotein and an increase in high density lipoprotein and serum insulin levels were observed in diabetic rats compared to diabetic controls after 2 weeks of treatment with plant extract and glibenclamide (p<0.05 each).When plant extract and drug treated diabetic rats were compared, a significant difference in the levels of blood glucose, insulin, total cholesterol and triglyceride levels were noted after 2 and 3 weeks of treatment. Acacia-nilotica leaves extract resulted in hypoglycaemic and hypolipidaemic effect in alloxan-induced diabetic rats similar to glibenclamide.

  4. Dietary avocado oil supplementation attenuates the alterations induced by type I diabetes and oxidative stress in electron transfer at the complex II-complex III segment of the electron transport chain in rat kidney mitochondria.

    PubMed

    Ortiz-Avila, Omar; Sámano-García, Carlos Alberto; Calderón-Cortés, Elizabeth; Pérez-Hernández, Ismael H; Mejía-Zepeda, Ricardo; Rodríguez-Orozco, Alain R; Saavedra-Molina, Alfredo; Cortés-Rojo, Christian

    2013-06-01

    Impaired complex III activity and reactive oxygen species (ROS) generation in mitochondria have been identified as key events leading to renal damage during diabetes. Due to its high content of oleic acid and antioxidants, we aimed to test whether avocado oil may attenuate the alterations in electron transfer at complex III induced by diabetes by a mechanism related with increased resistance to lipid peroxidation. 90 days of avocado oil administration prevented the impairment in succinate-cytochrome c oxidoreductase activity caused by streptozotocin-induced diabetes in kidney mitochondria. This was associated with a protection against decreased electron transfer through high potential chain in complex III related to cytochromes c + c1 loss. During Fe(2+)-induced oxidative stress, avocado oil improved the activities of complexes II and III and enhanced the protection conferred by a lipophilic antioxidant against damage by Fe(2+). Avocado oil also decreased ROS generation in Fe(2+)-damaged mitochondria. Alterations in the ratio of C20:4/C18:2 fatty acids were observed in mitochondria from diabetic animals that not were corrected by avocado oil treatment, which yielded lower peroxidizability indexes only in diabetic mitochondria although avocado oil caused an augment in the total content of monounsaturated fatty acids. Moreover, a protective effect of avocado oil against lipid peroxidation was observed consistently only in control mitochondria. Since the beneficial effects of avocado oil in diabetic mitochondria were not related to increased resistance to lipid peroxidation, these effects were discussed in terms of the antioxidant activity of both C18:1 and the carotenoids reported to be contained in avocado oil.

  5. Glucose Intolerance and Hyperlipidemia Prior to Diabetes Onset in Female Spontaneously Diabetic Torii (SDT) Rats

    PubMed Central

    Oikawa, Toshihiro; Sato, Kahei; Kanazawa, Yasunori

    2004-01-01

    The Spontaneously Diabetic Torii (SDT) rat, a newly established animal model for diabetes mellitus, presents nonobese type 2 diabetes with ocular complications. In the present study, oral glucose tolerance tests and biochemical and histopathological examinations were performed in female SDT rats at 16 and/or 25 weeks of age, before the onset of diabetes. At 25 weeks of age, glucose tolerance was significantly impaired, and plasma immunoreactive insulin levels at 120 min after glucose loading were significantly higher (P < 0.05). Body weight and fasting levels of plasma triglycerides and nonesterified fatty acids were significantly higher than those in control animals. Histopathologically, inflammatory cell infiltration and fibrosis were observed in and around the pancreatic islets. These results strongly suggest that female SDT rats are useful as a model to investigate impairment of glucose tolerance and hyperlipidemia prior to the onset of diabetes. PMID:15763939

  6. The protective effect of vanadium against diabetic cataracts in diabetic rat model.

    PubMed

    Sun, Lei; Shi, De-Jing; Gao, Xiang-Chun; Mi, Shu-Yong; Yu, Ying; Han, Qing

    2014-05-01

    The present study was designed to investigate the effect of vanadium in alloxan-induced diabetes and cataract in rats. Different doses of vanadium was administered once daily for 8 weeks to alloxan-induced diabetic rats. To know the mechanism of action of vanadium, lens malondialdehyde (MDA), protein carbonyl content, activity of superoxide dismutase (SOD), activities of aldose reductase (AR), and sorbitol levels were assayed, respectively. Supplementation of vanadium to alloxan-induced diabetic rats decreased the blood glucose levels due to hyperglycemia, inhibited the AR activity, and delayed cataract progression in a dose-dependent manner. The observed beneficial effects may be attributed to polyol pathway activation but not decreased oxidative stress. Overall, the results of this study demonstrate that vanadium could effectively reduce the alloxan-induced hyperglycemia and diabetic cataracts in rats.

  7. Febuxostat ameliorates diabetic renal injury in a streptozotocin-induced diabetic rat model.

    PubMed

    Lee, Hong-Joo; Jeong, Kyung Hwan; Kim, Yang Gyun; Moon, Joo Young; Lee, Sang Ho; Ihm, Chun Gyoo; Sung, Ji Youn; Lee, Tae Won

    2014-01-01

    Oxidative stress and inflammation are known to play central roles in the development of diabetic nephropathy (DN). Febuxostat is a novel non-purine xanthine oxidase (XO)-specific inhibitor developed to treat hyperuricemia. In this study, we investigated whether febuxostat could ameliorate DN via renoprotective mechanisms such as alleviation of oxidative stress and anti-inflammatory actions. Male Sprague-Dawley rats were divided into three groups: a normal group, a diabetes group (DM group), and a febuxostat-treated diabetes group (DM+Fx group). We administered 5 mg/kg of febuxostat to experimental rats for 7 weeks and evaluated clinical and biochemical parameters and XO and xanthine dehydrogenase (XDH) activity in hepatic tissue. The degree of oxidative stress and extent of inflammation were evaluated from urine samples and renal tissue collected from each group. Diabetic rats (DM and DM+Fx groups) had higher blood glucose and kidney weight relative to body weight than normal rats. Albuminuria was significantly reduced in febuxostat-treated diabetic rats compared with untreated diabetic rats. Quantitative analysis showed that hepatic XO and XDH activities were higher in the DM groups, but decreased after treatment with febuxostat. Urinary 8-OHdG concentrations and renal cortical nitrotyrosine also indicated reduced oxidative stress in the DM+Fx group relative to the DM group. The number of ED-1-stained cells in the glomerulus and tubule of diabetic renal tissue decreased in febuxostat-treated diabetic rats relative to that of non-treated diabetic rats. Diabetic rats also expressed higher transcript levels of inflammatory genes (E-selectin and VCAM-1), an inflammation-induced enzyme (COX-2), and inflammatory mediators (ED-1 and NF-κB) than control rats; expression of these genes was significantly reduced by treatment with febuxostat. Febuxostat prevents diabetic renal injury such as albuminuria. This renoprotective effect appears to be due to attenuation of the

  8. Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase.

    PubMed

    Winiarska, Katarzyna; Dzik, Jolanta M; Labudda, Mateusz; Focht, Dorota; Sierakowski, Bartosz; Owczarek, Aleksandra; Komorowski, Lukasz; Bielecki, Wojciech

    2016-01-01

    Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of animals: (i) untreated lean (?/+) Zucker diabetic fatty (ZDF) rats; (ii) untreated obese diabetic (fa/fa) ZDF rats; and (iii) ZDF fa/fa rats treated with melatonin (20 mg/L) in drinking water. Urinary albumin excretion was measured weekly. After 4 wk of the treatment, the following parameters were determined in kidney cortex: Nox activity, expression of subunits of the enzyme, their phosphorylation and subcellular distribution. Histological studies were also performed. Compared to ?/+ controls, ZDF fa/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47(phox) subunits, elevated level of p47(phox) phosphorylation, and enlarged phospho-p47(phox) and p67(phox) content in membrane. Melatonin administration to ZDF fa/fa rats resulted in the improvement of renal functions, as manifested by considerable attenuation of albuminuria and some amelioration of structural abnormalities. The treatment turned out to nearly normalize Nox activity, which was accompanied by considerably lowered expression and diminished membrane distribution of regulatory subunits, that is, phospho-p47(phox) and p67(phox) . Thus, it is concluded that: (i) melatonin beneficial action against diabetic nephropathy involves attenuation of the excessive activity of Nox; and (ii) the mechanism of melatonin inhibitory effect on Nox is based on the mitigation of expression and membrane translocation of its regulatory subunits.

  9. Diabetic foot ulcers: Part II. Management.

    PubMed

    Alavi, Afsaneh; Sibbald, R Gary; Mayer, Dieter; Goodman, Laurie; Botros, Mariam; Armstrong, David G; Woo, Kevin; Boeni, Thomas; Ayello, Elizabeth A; Kirsner, Robert S

    2014-01-01

    The management of diabetic foot ulcers can be optimized by using an interdisciplinary team approach addressing the correctable risk factors (ie, poor vascular supply, infection control and treatment, and plantar pressure redistribution) along with optimizing local wound care. Dermatologists can initiate diabetic foot care. The first step is recognizing that a loss of skin integrity (ie, a callus, blister, or ulcer) considerably increases the risk of preventable amputations. A holistic approach to wound assessment is required. Early detection and effective management of these ulcers can reduce complications, including preventable amputations and possible mortality. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  10. Elevated glutamine metabolism in splenocytes from spontaneously diabetic BB rats.

    PubMed

    Wu, G Y; Field, C J; Marliss, E B

    1991-02-15

    To investigate the metabolic fates of glutamine in splenocytes from the BB rat with spontaneous immunologically mediated insulin-dependent diabetes, freshly isolated cells were incubated in Krebs-Ringer Hepes buffer with 1.0 mM-[U-14C]glutamine and 0, 4 mM- or 15 mM-glucose. (1) The major products of glutamine metabolism in splenocytes from normal and diabetic rats were ammonia, glutamate, aspartate and CO2. (2) The addition of glucose increased (P less than 0.01) glutamate production, but decreased (P less than 0.01) aspartate and CO2 production from glutamine, as compared with the values obtained in the absence of glucose. However, there were no differences in these metabolites of glutamine at 4 mM- and 15 mM-glucose. (3) At all glucose concentrations used, the productions of ammonia, glutamate, aspartate and CO2 from glutamine were all markedly increased (P less than 0.01) in splenocytes from diabetic rats. (4) Potential ATP production from glutamine in the splenocytes was similar to that from glucose, and was increased in cells from the diabetic rat. (5) ATP concentrations were increased (P less than 0.01) in diabetic-rat splenocytes in the presence of glutamine with or without glucose. (6) Our results demonstrate that glutamine is an important energy substrate for splenocytes and suggest that the increased glutamine metabolism may be associated with the activation of certain subsets of splenocytes in the immunologically mediated diabetic syndrome.

  11. Effects of Atorvastatin on Nitrate Tolerance in Diabetic Rats

    PubMed Central

    Imenshahidi, Mohsen; Karimi, Gholamreza; Kazemzadeh, Ehsan

    2010-01-01

    Statins have been reported to show preventive effect on nitrate tolerance in normal rats, but there are no reports on their effect in diabetic animals. In this study, diabetes was induced in male wistar rats by a single intraperitoneal injection of streptozotocin (45 mg/kg). Five groups of diabetic and five groups of normal rats were treated; groups 1 (of normal and diabetic rats) received atorvastatin (10 mg/kg/d p.o. for 8 weeks) and groups 2 received atorvastatin (10 mg/kg/d p.o. for last 3 days). Groups 3 and groups 4 were similar to groups 1 and 2 respectively, except that they received nitroglycerin (50 mg/kg/d, b.i.d. for last 3 days of the study). Groups 5 received neither atorvastatin nor nitroglycerin. After 8 weeks, relaxations to nitroglycerin (0.01 to 10 nM) and nitroprusside (0.01 to 10 nM) were determined on phenylephrine-preconstricted aortic rings. The relaxation response to nitroglycerin in diabetic and normal aorta were not significantly different. The results showed that 8 weeks treatment with atorvastatin prevents nitrate tolerance in diabetic and normal rats, but in nitrate tolerant animals, 3 days treatment with atorvastatin was not effective on protection against nitrate tolerance. PMID:24363707

  12. Timing behavior in streptozotocin-induced diabetic rats.

    PubMed

    Orduña, Vladimir; Hong, Enrique; Bouzas, Arturo

    2011-10-10

    There is evidence of deterioration of spatial cognition in streptozotocin (STZ)-induced diabetic rats. Here, we evaluate a possible dissociation in the cognitive deficits due to diabetes by examining another crucial aspect of animal cognition: temporal perception. Timing behavior and temporal memory were evaluated in STZ-induced diabetic rats employing two timing tasks: the peak-interval procedure, with its Gap variant, and the interval bisection task. A spatial memory task, rewarded alternation in the T-maze, was also evaluated to explore spatial cognition. The two timing tasks employed coincide in the finding of a normal timing performance in STZ-induced diabetic rats. The peak-interval procedure provided results that suggest that the timing behavior is equally accurate and precise than in control subjects; in the Gap procedure, an equal change in peak time in both groups indicates that temporal working memory is also intact. In the interval bisection task, we analyzed the acquisition of a temporal discrimination and the sensitivity to changes in the duration of the stimulus; no differences were found in either the acquisition process or the sensitivity index. In contrast, in the rewarded alternation task, STZ-induced diabetic rats exhibited a significant deficit in spatial cognition. The cognitive processes involved in timing behavior and temporal memory are not deteriorated as a consequence of diabetes; the cognitive deficits associated to diabetes thus seem to be restricted to the spatial domain.

  13. Hemodynamic alterations in chronically conscious unrestrained diabetic rats.

    PubMed

    Carbonell, L F; Salom, M G; Garcia-Estañ, J; Salazar, F J; Ubeda, M; Quesada, T

    1987-05-01

    Important cardiovascular dysfunctions have been described in streptozotocin (STZ)-diabetic rats. To determine the influence of these changes on the hemodynamic state and whether insulin treatment can avoid them, different hemodynamic parameters, obtained by the thermodilution method, were studied in STZ-induced (65 mg/kg) diabetic male Wistar rats, as well as in age-control, weight-control, and insulin-treated diabetic ones. All rats were examined in the conscious, unrestrained state 12 wk after induction of diabetes or acidified saline (pH 4.5) injection. At 12 wk of diabetic state most important findings were normotension, high blood volume, bradycardia, increase in stroke volume, cardiac output, and cardiosomatic ratio, and decrease in total peripheral resistance and cardiac contractility and relaxation (dP/dtmax and dP/dtmin of left ventricular pressure curves). The insulin-treated diabetic rats did not show any hemodynamic differences when compared with the control animals. These results suggest that important hemodynamic alterations are present in the chronic diabetic state, possibly conditioning congestive heart failure. These alterations can be prevented by insulin treatment.

  14. Effect of diabetes on glycogen metabolism in rat retina.

    PubMed

    Sánchez-Chávez, Gustavo; Hernández-Berrones, Jethro; Luna-Ulloa, Luis Bernardo; Coffe, Víctor; Salceda, Rocío

    2008-07-01

    Glucose is the main fuel for energy metabolism in retina. The regulatory mechanisms that maintain glucose homeostasis in retina could include hormonal action. Retinopathy is one of the chemical manifestations of long-standing diabetes mellitus. In order to better understand the effect of hyperglycemia in retina, we studied glycogen content as well as glycogen synthase and phosphorylase activities in both normal and streptozotocin-induced diabetic rat retina and compared them with other tissues. Glycogen levels in normal rat retina are low (46 +/- 4.0 nmol glucosyl residues/mg protein). However, high specific activity of glycogen synthase was found in retina, indicating a substantial capacity for glycogen synthesis. In diabetic rats, glycogen synthase activity increased between 50% and 100% in retina, brain cortex and liver of diabetic rats, but only retina exhibited an increase in glycogen content. Although, total and phosphorylated glycogen synthase levels were similar in normal and diabetic retina, activation of glycogen synthase by glucose-6-P was remarkable increased. Glycogen phosphorylase activity decreased 50% in the liver of diabetic animals; it was not modified in the other tissues examined. We conclude that the increase in glycogen levels in diabetic retina was due to alterations in glycogen synthase regulation.

  15. Influence of streptozotocin-induced diabetes and insulin treatment on the pituitary-testicular axis during sexual maturation in rats.

    PubMed

    Sudha, S; Valli, G; Julie, P M; Arunakaran, J; Govindarajulu, P; Balasubramanian, K

    2000-01-01

    Effects of streptozotocin (STZ)-diabetes and insulin treatment on the functioning of pituitary-testicular axis during sexual maturation was studied. Prepubertal (30 days old) and pubertal (50 days old) male Wistar rats were made diabetic by a single injection of STZ. A group of diabetic rats was given insulin (3U/100 g b.wt./day in 2 equally divided doses), 3 days after STZ treatment. Prepubertal and pubertal rats of all groups were killed on postnatal days 51 and 71, respectively. STZ-diabetes caused marked reduction in serum LH, FSH, prolactin, testosterone and testicular interstitial fluid testosterone as well as the activities of Leydig cellular steroidogenic enzymes (3beta-and 17beta-hydroxysteroid dehydrogenases). Insulin treatment to diabetic rats maintained these changes at control range except FSH and prolactin in prepubertal rats. The results indicate that (i) diabetes-induced steroidogenic lesions in Leydig cells represent a direct consequence of dysfunctioning of pituitary-testicular axis, (ii) the adverse effects of diabetes on pituitary-testicular functions are influenced by age of its induction and (iii) optimum insulin level is essential for the acquisition of Leydig cellular steroidogenic efficacy during sexual development.

  16. The effect of dietary Cu and diabetes on indices of Cu nutriture in the rat

    SciTech Connect

    Rucker, R.B.; Uriu-Hare, J.Y.; Tinker, D.; Keen, C.L. )

    1991-03-11

    The uptake-retention of 67Cu is affected by dietary Cu and diabetes. Consequently, the functional activities of select enzymes and tissue Cu status were assessed. STZ-diabetic and control rats were fed Cu suppl. or def. diets. Rats were gavaged with 28 {mu}Ci 67Cu, and killed 8, 16, 24, 32, 64, or 128 h later. Diabetic rats were hyperphagic, hyperglycemic and hypoinsulinemic; with no effect of diet. Plasma ceruloplasmin activity (Cp) was lower in Cu def. rats; diabetic rats tended to have higher Cp than controls. Cu def. rats had low Cu levels in liver, kidney and plasma. Cu suppl. diabetic rats had higher liver and kidney Cu compared to Cu def. diabetic rats. Gel chromatography of liver showed that with time, there was a transfer of 67Cu from low to higher MW ligands. In nondiabetic rats, more 67Cu was associated with the higher MW ligands. The converse was observed for diabetic rats. There was no effect of diabetes on liver 67Cu localization. Diabetic rats had higher metallothionein (MT) concentrations in liver and kidney compared to controls Cu deficiency lowered MT values in both diabetic and control rats. CuZn SOD Cu activity was lowered with Cu def. and diabetes, while Mn SOD activity was similar among groups. Plasma lipid peroxide levels were lower in diabetic rats than controls. The results show that Cu metabolism is affected in diabetes, and the changes are functionally significant.

  17. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    PubMed Central

    Okamura, Tadashi; Pei, Xiang Yuan; Miyoshi, Ichiro; Shimizu, Yukiko; Takanashi-Yanobu, Rieko; Mototani, Yasumasa; Kanai, Takao; Satoh, Jo; Kimura, Noriko; Kasai, Noriyuki

    2013-01-01

    Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus. PMID:23691528

  18. Arginase II Deletion Increases Corpora Cavernosa Relaxation in Diabetic Mice

    PubMed Central

    Toque, Haroldo; Tostes, Rita; Yao, Lin; Xu, Zhimin; Webb, Clinton R.; Caldwell, Ruth; Caldwell, Robert

    2010-01-01

    Introduction Diabetes-induced erectile dysfunction involves elevated arginase (Arg) activity and expression. Because nitric oxide (NO) synthase and Arg share and compete for their substrate L-arginine, NO production is likely linked to regulation of Arg. Arg is highly expressed and implicated in erectile dysfunction. Aim It was hypothesized that Arg-II isoform deletion enhances relaxation function of corpora cavernosal (CC) smooth muscle in a streptozotocin (STZ) diabetic model. Methods Eight weeks after STZ-induced diabetes, vascular functional studies, Arg activity assay, and protein expression levels of Arg and constitutive NOS (using western blots) were assessed in CC tissues from non-diabetic wild type (WT), diabetic (D) WT (WT+D), Arg-II knockout (KO) and Arg-II KO+D mice (N=8–10 per group). Main Outcome Measures Inhibition or lack of arginase results in facilitation of CC relaxation in diabetic CC. Results Strips of CC from Arg-II KO mice exhibited an enhanced maximum endothelium-dependent relaxation (from 70+3% to 84+4%) and increased nitrergic relaxation (by 55%, 71%, 42%, 42%, and 24% for 1, 2, 4, 8 and 16 Hz, respectively) compared to WT mice. WT+D mice showed a significant reduction of endothelium-dependent maximum relaxation (44+8%), but this impairment of relaxation was significantly prevented in Arg-II KO+D mice (69+4%). Sympathetic-mediated and alpha-adrenergic agent-induced contractile responses also were increased in CC strips from D compared to non-D controls. Contractile responses were significantly lower in Arg-II KO control and D versus the WT groups. WT+D mice increased Arg activity (1.5-fold) and Arg-II protein expression and decreased total and phospho-eNOS at Ser-1177, and nNOS levels. These alterations were not seen in Arg-II KO mice. Additionally, the Arg inhibitor BEC (50 μM) enhanced nitrergic and endothelium-dependent relaxation in CC of WT+D mice. Conclusion These studies show for the first time that Arg-II deletion improves CC

  19. Cytoprotective effect of silymarin against diabetes-induced cardiomyocyte apoptosis in diabetic rats.

    PubMed

    Tuorkey, Muobarak J; El-Desouki, Nabila I; Kamel, Rabab A

    2015-01-01

    The beneficial effects of silymarin have been extensively studied in the context of inflammation and cancer treatment, yet much less is known about its therapeutic effect on diabetes. The present study was aimed to investigate the cytoprotective activity of silymarin against diabetes-induced cardiomyocyte apoptosis. Rats were randomly divided into: control group, untreated diabetes group and diabetes group treated with silymarin (120 mg/kg•d) for 10 d. Rats were sacrificed, and the cardiac muscle specimens and blood samples were collected. The immunoreactivity of caspase-3 and Bcl-2 in the cardiomyocytes was measured. Total proteins, glucose, insulin, creatinine, AST, ALT, cholesterol, and triglycerides levels were estimated. Unlike the treated diabetes group, cardiomyocyte apoptosis increased in the untreated rats, as evidenced by enhanced caspase-3 and declined Bcl-2 activities. The levels of glucose, creatinine, AST, ALT, cholesterol, and triglycerides declined in the treated rats. The declined levels of insulin were enhanced again after treatment of diabetic rats with silymarin, reflecting a restoration of the pancreatic β-cells activity. The findings of this study are of great importance, which confirmed for the first time that treatment of diabetic subjects with silymarin may protect cardiomyocytes against apoptosis and promote survival-restoration of the pancreatic β-cells. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  20. Serum markers for type II diabetes mellitus

    DOEpatents

    Metz, Thomas O; Qian, Wei-Jun; Jacobs, Jon M; Polpitiya, Ashoka D; Camp, II, David G; Smith, Richard D

    2014-03-18

    A method for identifying persons with increased risk of developing type 2 diabetes mellitus utilizing selected biomarkers described hereafter either alone or in combination. The present invention allows for broad based, reliable, screening of large population bases and provides other advantages, including the formulation of effective strategies for characterizing, archiving, and contrasting data from multiple sample types under varying conditions.

  1. Ileal brake failure in streptozotocin-induced diabetic rat.

    PubMed

    Martín, M T; Azpiroz, F; Malagelada, J R

    2004-05-01

    Diabetes mellitus frequently alters gastrointestinal function, but the pathophysiology of the diabetic gut has not been fully elucidated. Our aim was to characterize the enterogastric modulation of gastric emptying in an experimental model of diabetic rat and to determine the putative consequences of impaired regulation on glycaemic control. Studies were performed in streptozotozin-induced diabetic and control groups of male Sprague-Dawley rats. In rats fitted with chronic ileal cannulae, gastric emptying of a peptide meal was measured during ileal infusion of either lipids (ileal brake) or saline. The influence of the ileal brake mechanism on blood glucose levels after oral administration of a glucose solution was also evaluated. Diabetic rats exhibited a precipitous gastric emptying (80% +/- 3% versus 57% +/- 3% in controls; P < 0.05). Ileal lipids delayed gastric emptying in control (38 +/- 4%; P < 0.05 versus ileal saline) but not in diabetic animals (77 +/- 5%; N.S. versus ileal saline). As the ileal brake contributes to the management of postprandial blood glucose levels (114 +/- 4.9 mg/dL after ileal lipids versus 134 +/- 7.8 mg/dL after ileal saline in control rats; P < 0.05), the failure of this mechanism in diabetic rats worsens glycaemic control after feeding (455 +/- 20.4 mg/dL after ileal lipids versus 399 +/- 8.7 mg/dL after ileal saline; P < 0.05). Experimental diabetes impairs the ileal brake mechanism and disturbs gastric emptying. These abnormalities may contribute to difficult glycaemic control.

  2. Cardiovascular effects of endomorphins in alloxan-induced diabetic rats.

    PubMed

    Liu, Jing; Yu, Ye; Fan, Ying-zhe; Chang, Hui; Liu, Hong-mei; Cui, Yun; Chen, Qiang; Wang, Rui

    2005-04-01

    Endomorphins, the endogenous, potent and selective mu-opioid receptor agonists, have been shown to decrease systemic arterial pressure (SAP) in rats. In the present study, responses to endomorphins were investigated in systemic vascular bed of alloxan-induced diabetic rats and in non-diabetic rats. Diabetes was induced by alloxan (220 mg/kg, i.p.) in male Wistar rats. At 4-5 weeks after the onset of diabetes, intravenous injections of endomorphins (1-30 nmol/kg) led to an increase of SAP and heart rate (HR) consistently and dosed-dependently. SAP increased 7.68+/-3.73, 11.19+/-4.55, 21.19+/-2.94 and 27.48+/-6.21% from the baseline at the 1, 3, 10 and 30 nmol/kg dose, respectively, of endomorphin 1 (n=4; p<0.05), and similar changes were observed in response to endomorphin 2. The hypertension could be antagonized markedly by i.p. 2 mg/kg of naloxone. On the other hand, bilateral vagotomy would attenuate the effects of hypertension and diminished the changes of HR in response to endomorphins. With diabetic rats, 6-10 weeks after the induction of diabetes, intravenous injections of endomorphins produced non-dose-related various changes in SAP, such as a single decrease, or a single increase, or biphasic changes characterized by an initial decrease followed by a secondary increase, or no change at all. These results suggest that diabetes may lead to the dysfunction of the cardiovascular system in response to endomorphins. Furthermore, the diabetic rats of 4-5 weeks after alloxan-treatment, the increase in SAP and HR caused by i.v. endomorphins might be explained by a changed effect of vagus and by a naloxone-sensitive mechanism.

  3. Prevention of diabetes in rats by bone marrow transplantation.

    PubMed

    Alinaji; Silvers, W K; Bellgrau, D; Anderson, A O; Plotkin, S; Barker, C F

    1981-09-01

    Hyperglycemia, hypoinsulinemia and ketonemia often develop abruptly in previously normal young "BB" rats. The syndrome mimics human juvenile diabetes closely and is, thus, appropriate for assessing pancreatic transplantation. Transplantation of islet cells from closely histocompatible Wistar Furth (WF) donor resulted in permanent normoglycemia when immunosuppression with ALS was given. However, when islet cells from nondiabetic "BB" donors were transplanted to nonimmunosuppressed diabetic "BB" recipients, only transient normoglycemia followed. Transplantation of WF islets cells also failed in diabetic "BB" rats which were tolerant of WF antigens, again suggesting destruction of transplanted islet cells by the original disease process-possibly autoimmunity. Evidence for autoimmunity was strengthened by the finding that newly diabetic "BB" rats could be rendered normoglycemic by immunosuppression. Since genetic susceptibility to spontaneous autoimmune diabetes is unique to some members of the "BB" stock, an attempt was made to alter their vulnerability by modifying their cellular immune system. Accordingly, 50 million bone marrow cells from WF donors were inoculated into half the newborn members of "BB" litters, leaving the littermates as unmodified controls. Most bone marrow recipients were protected, only four of 37 (10.8%) ever becoming diabetic, while the incidence of diabetes in noninoculated littermates was 22 of 39 (56.4%). The ultimate goal in human diabetes, which also seems very likely to be an autoimmune disease, may not be replacement of destroyed islet cells but identification of potentially susceptible children and prevention of islet destruction by immunologic manipulation.

  4. Cardioprotective Effect of Sodium Ferulate in Diabetic Rats

    PubMed Central

    Xu, Xiaohong; Xiao, Haijuan; Zhao, Jiangpei; Zhao, Tongfeng

    2012-01-01

    Reactive oxygen species (ROS) play important roles in the occurrence and development in diabetic cardiomyopathy (DC). Ferulic acid is one of the ubiquitous compounds in diet. Sodium ferulate (SF) is its sodium salt. SF has potent free radical scavenging activity and can effectively scavenge ROS. The study investigated the effect of SF on cardioprotection in diabetic rats. The diabetic rats induced by streptozotocin (STZ) were treated with SF (110mg/kg) by gavage per day for 12 weeks. Results showed that the levels of nitric oxide (NO) and superoxide dismutase (SOD) activity in plasma and myocardium in SF-treated group were significantly higher than those in diabetic control group. The levels of malondialdehyde (MDA) in plasma and myocardium in SF-treated group were significantly lower than those in diabetic control group. Expression of connective tissue growth factor (CTGF) in myocardium in SF-treated group was apparently lower than that in diabetic control group. Compared with normal control group, electron micrographs of myocardium in diabetic control group showed apparently abnormality, while that was significantly ameliorated in SF-treated group. The study demonstrated that SF has a cardioprotective effect via increasing SOD activity and NO levels in plasma and myocardium, inhibiting oxidative stress in plasma and myocardium, and inhibiting the expression of CTGF in myocardium in diabetes rats. PMID:22701336

  5. Anti-Diabetic Effect of Portulaca oleracea L. Polysaccharideandits Mechanism in Diabetic Rats

    PubMed Central

    Bai, Yu; Zang, Xueli; Ma, Jinshu; Xu, Guangyu

    2016-01-01

    Diabetes mellitus (DM) is a metabolic syndrome caused by multiple genetic and environmental factors. Traditional Chinese medicine preparations have shown a comprehensive and function-regulating characteristic. Purslane (Portulaca oleracea L.) is an annual succulent herb. Currently, there have been some related reports on the treatment of diabetes with purslane. The current study was designed to separate and purify the polysaccharide, a systematic study of its physical and chemical properties, antioxidant activity, and anti-diabetic mechanism, in order to provide a theoretical basis for the development of drugs of purslane. A crude water soluble polysaccharide extracted from purslane was named CPOP (crude Portulaca oleracea L. polysaccharide). Effects of CPOP on bodyweight, glucose tolerance test (GTT), fasting blood glucose (FBG), fasting serum insulin (FINS), insulin sensitivity index (ISI), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), methane dicarboxylic aldehyde (MDA), and superoxygen dehydrogenises (SOD) were investigated. The results indicate that the oral administration of CPOP could significantly increase the body weight and significantly improve the glucose tolerance in diabetic rats. Meanwhile, CPOP could significantly reduce the FBG level, and elevate the FINS level and ISI value in diabetic rats. In addition, CPOP could significantly reduce TNF-α and IL-6 levels in diabetic rats; CPOP could also reduce MDA and SOD activities in the liver tissue of diabetic rats. These results suggest that the anti-diabetic effect of CPOP may be associated with its antioxidant and anti-inflammatory effects. PMID:27463713

  6. Aminoguanidine prevents impaired healing and deficient angiogenesis in diabetic rats.

    PubMed

    Teixeira, A S; Caliari, M V; Rocha, O A; Machado, R D; Andrade, S P

    1999-12-01

    The diabetic organism is unable to produce normal amount of granulation tissue which results in delayed wound healing, a significant clinical problem. In the present study, the effect of oral administration of aminoguanidine (AG), in the diabetes-induced inhibition of angiogenesis and granulation tissue formation was tested. Subcutaneous implantation of sponge discs in nondiabetic rats induced a wound repair response as determined by the amount of hemoglobin (vascular index) and granulation tissue formation (morphometric analysis) of the implants. In the streptozotocin-induced diabetic rats the predominant response indicative of healing was inhibitory. Aminoguanidine was effective in preventing in 50% the diabetes-induced inhibition of fibrovascular tissue growth in the implants, as indicated by the values of hemoglobin content and vascular growth areas of the implants. These results indicate that AG holds potential therapeutic value in the management of healing impairment of the diabetic condition.

  7. Effects of experimental diabetes on the responsiveness of rat aorta.

    PubMed Central

    Mulhern, M.; Docherty, J. R.

    1989-01-01

    1. Vascular responsiveness was examined in aortic ring preparations, with or without endothelium, from rats with experimental diabetes induced by streptozotocin and from vehicle-treated (control) rats. 2. There were no significant differences between diabetic tissues and control tissues in the responsiveness to the vasoconstrictors noradrenaline, 5-hydroxytryptamine and KCl, and to the vasodilators sodium nitroprusside, isoprenaline and acetylcholine. 3. When maximum contractions to vasoconstrictors was expressed relative to tissue weight, maximum contractions were significantly greater in diabetic tissues. 4. When expressed in terms of the KCl contraction, there were no significant differences between diabetic and control tissues in the maximum contraction to vasoconstrictors. 5. These results demonstrate that diabetic-induced changes in vascular responsiveness, if any, do not occur at the receptor level. PMID:2790373

  8. Macrovascular complications in Mexican Americans with type II diabetes.

    PubMed

    Haffner, S M; Mitchell, B D; Stern, M P; Hazuda, H P

    1991-07-01

    Mexican Americans have a threefold greater prevalence of non-insulin-dependent (type II) diabetes mellitus than non-Hispanic whites in the San Antonio Heart Study, a population-based study of diabetes. In addition, Mexican-American diabetic subjects (n = 365) have greater fasting glycemia than non-Hispanic white diabetic subjects (P less than 0.001). Despite these findings, and despite a higher prevalence of microvascular complications among Mexican Americans, there does not appear to be a marked difference in prevalence of macrovascular complications between Mexican-American and non-Hispanic white diabetic subjects. Mexican-American diabetic subjects have only a moderate excess of peripheral vascular disease (as judged by ankle-arm blood pressure ratios) relative to non-Hispanic white diabetic subjects (sex-adjusted Mantel-Haenszel odds ratio 1.84, 95% confidence interval 0.75-4.49). Mexican-American diabetic subjects actually reported fewer myocardial infarctions than non-Hispanic white diabetic subjects (sex-adjusted Mantel-Haenszel odds ratio 0.73, 95% confidence interval 0.31-1.71). Duration was not associated with either peripheral vascular disease or myocardial infarction. Severity of glycemia was only mildly associated with presence of peripheral vascular disease and negatively associated with self-reported myocardial infarction. This latter finding may represent a survival bias in that more severe diabetic subjects have already died and are not ascertained in a prevalence study. The absence of an ethnic difference in the prevalence of macrovascular disease contrasts with our previous reports from the San Antonio Heart Study, in which the prevalence of both retinopathy and proteinuria was observed to be higher in Mexican-American diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats.

    PubMed

    Kurtz, M; Capobianco, E; Careaga, V; Martinez, N; Mazzucco, M B; Maier, M; Jawerbaum, A

    2014-03-01

    Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4 (LTB4, PPARα ligand) or 15deoxyΔ(12,14)prostaglandin J2 (15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4 and partially restored by 15dPGJ2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

  10. Targeting heme oxygenase-1 in early diabetic nephropathy in streptozotocin-induced diabetic rats.

    PubMed

    Abo El Gheit, R; Emam, M N

    2016-12-01

    Diabetic nephropathy (DN) is one of the most common microvascular diabetic complications. This study was designed to evaluate the possible protective effect and underlying mechanisms of HO-1 induction in streptozotocin (STZ)-induced early DN in rats. The diabetic rats were divided into three groups: STZ-diabetic, cobalt protoporphyrin (CoPP)-treated diabetic, and zinc protoporphyrin IX (ZnPP)-treated diabetic groups. Compared to the STZ-diabetic group, CoPP-induced HO-1 upregulation improved the diabetic state and renal functional parameters, suppressed the renal proinflammatory marker, NF-κB, abrogated the elevated renal hydroxyprolin, and decreased the enhanced renal nicotinamide adenine dinucleotide phosphate oxidase activity with parallel reduction of urinary oxidative stress markers. On the contrary, treatment with ZnPP abrogated HO-1 levels, aggravated the diabetic condition with further increases in renal oxidative stress, fibrotic and inflammatory markers, and exacerbated renal dysfunction in diabetic animals. These findings suggest that the reduced diabetic renal injury upon HO-1 induction implicates the role of HO-1 induction as a potential treatment for DN.

  11. Angiotensin II induces differential insulin action in rat skeletal muscle.

    PubMed

    Surapongchai, Juthamard; Prasannarong, Mujalin; Bupha-Intr, Tepmanas; Saengsirisuwan, Vitoon

    2017-03-01

    Angiotensin II (ANGII) is reportedly involved in the development of skeletal muscle insulin resistance. The present investigation evaluated the effects of two ANGII doses on the phenotypic characteristics of insulin resistance syndrome and insulin action and signaling in rat skeletal muscle. Male Sprague-Dawley rats were infused with either saline (SHAM) or ANGII at a commonly used pressor dose (100 ng/kg/min; ANGII-100) or a higher pressor dose (500 ng/kg/min; ANGII-500) via osmotic minipumps for 14 days. We demonstrated that ANGII-100-infused rats exhibited the phenotypic features of non-obese insulin resistance syndrome, including hypertension, impaired glucose tolerance and insulin resistance of glucose uptake in the soleus muscle, whereas ANGII-500-treated rats exhibited diabetes-like symptoms, such as post-prandial hyperglycemia, impaired insulin secretion and hypertriglyceridemia. At the cellular level, insulin-stimulated glucose uptake in the soleus muscle of the ANGII-100 group was 33% lower (P < 0.05) than that in the SHAM group and was associated with increased insulin-stimulated IRS-1 Ser(307) and decreased Akt Ser(473) and AS160 Thr(642) phosphorylation and GLUT-4 expression. However, ANGII-500 infusion did not induce skeletal muscle insulin resistance or impair insulin signaling elements as initially anticipated. Moreover, we found that insulin-stimulated glucose uptake in the ANGII-500 group was accompanied by the enhanced expression of ACE2 and MasR proteins, which are the key elements in the non-classical pathway of the renin-angiotensin system. Collectively, this study demonstrates for the first time that chronic infusion with these two pressor doses of ANGII induced differential metabolic responses at both the systemic and skeletal muscle levels. © 2017 Society for Endocrinology.

  12. Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Kant, Vinay; Kumar, Dinesh; Kumar, Dhirendra; Prasad, Raju; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surender K

    2015-05-01

    Substance P (SP) is known to stimulate angiogenesis, fibroblasts proliferation and expressions of cytokines and growth factors involved in wound healing. However, SP level reduces in dermis in diabetics and, hence, it was hypothesized that exogenously applied SP could be helpful in improving wound healing in diabetic rats. Excision skin wound was created on the back of diabetic rats and rats were divided into three groups i.e. (i) saline-, (ii) gel- and (iii) SP-treated. Normal saline, pluronic gel and SP (10(-6)M) in gel were topically applied once daily for 19days. SP treatment significantly increased the wound closure, levels of interleukin-10, and expressions of vascular endothelial growth factor, transforming growth factor-beta1, heme oxygenase-1 and endothelial nitric oxide synthase, whereas it significantly decreased the expression of tumor necrosis factor-alpha, interleukin-1beta and matrix metalloproteinases-9 in the granulation/healing tissue. The inflammatory cells were present for long time in normal saline-treated group. Histological evaluation revealed better extracellular matrix formation with marked fibroblast proliferation and collagen deposition in SP-treated group. Early epithelial layer formation, increased microvessel density and greater growth associated protein-43 positive nerve fibers were also evidenced in SP-treated group. In conclusion, SP treatment markedly accelerated cutaneous wound healing in diabetic rats.

  13. Foreign Body Response to Subcutaneous Implants in Diabetic Rats

    PubMed Central

    Socarrás, Teresa Oviedo; Vasconcelos, Anilton C.; Campos, Paula P.; Pereira, Nubia B.; Souza, Jessica P. C.; Andrade, Silvia P.

    2014-01-01

    Implantation of synthetic matrices and biomedical devices in diabetic individuals has become a common procedure to repair and/or replace biological tissues. However, an adverse foreign body reaction that invariably occurs adjacent to implant devices impairing their function is poorly characterized in the diabetic environment. We investigated the influence of this condition on the abnormal tissue healing response in implants placed subcutaneously in normoglycemic and streptozotocin-induced diabetes in rats. In polyether-polyurethane sponge discs removed 10 days after implantation, the components of the fibrovascular tissue (angiogenesis, inflammation, fibrogenesis, and apoptosis) were assessed. Intra-implant levels of hemoglobin and vascular endothelial growth factor were not different after diabetes when compared with normoglycemic counterparts. However, there were a lower number of vessels in the fibrovascular tissue from diabetic rats when compared with vessel numbers in implants from non-diabetic animals. Overall, the inflammatory parameters (neutrophil accumulation - myeloperoxidase activity, tumor necrosis factor alpha, and monocyte chemotactic protein-1 levels and mast cell counting) increased in subcutaneous implants after diabetes induction. However, macrophage activation (N-acetyl-β-D-glucosaminidase activity) was lower in implants from diabetic rats when compared with those from normoglycemic animals. All fibrogenic markers (transforming growth factor beta 1 levels, collagen deposition, fibrous capsule thickness, and foreign body giant cells) decreased after diabetes, whereas apoptosis (TUNEL) increased. Our results showing that hyperglycemia down regulates the main features of the foreign body reaction induced by subcutaneous implants in rats may be relevant in understanding biomaterial integration and performance in diabetes. PMID:25372281

  14. Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats.

    PubMed

    Jin, Heung Yong; Lee, Kyung Ae; Song, Sun Kyung; Liu, Wei Jing; Choi, Ji Hae; Song, Chang Ho; Baek, Hong Sun; Park, Tae Sun

    2012-01-15

    We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, P<0.05) and skin blood flow was improved (10.90 ± 0.67 vs 8.85 ± 0.49 TPU, P<0.05) in the diabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6 ± 2.2 vs 49.8 ± 2.7 μm(2), P<0.05) and the intraepidermal nerve fiber density was significantly less reduced (6.27 ± 0.24 vs 5.40 ± 0.25/mm, P<0.05) in the diabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy.

  15. Effects of Cinnamomum zeylanicum (Ceylon cinnamon) on blood glucose and lipids in a diabetic and healthy rat model.

    PubMed

    Ranasinghe, Priyanga; Perera, Sanja; Gunatilake, Mangala; Abeywardene, Eranga; Gunapala, Nuwan; Premakumara, Sirimal; Perera, Kamal; Lokuhetty, Dilani; Katulanda, Prasad

    2012-04-01

    To evaluate short- and long-term effects of Cinnamomum zeylanicum on food consumption, body weight, glycemic control, and lipids in healthy and diabetes-induced rats. The study was conducted in two phases (Phase I and Phase II), using Sprague-Dawley rats in four groups. Phase I evaluated acute effects on fasting blood glucose (FBG) (Groups 1 and 2) and on post-oral glucose (Groups 3 and 4) blood glucose. Groups 1 and 3 received distilled-water and Groups 2 and 4 received cinnamon-extracts. Phase II evaluated effects on food consumption, body weight, blood glucose, and lipids over 1 month. Group A (n = 8, distilled-water) and Group B (n = 8, cinnamon-extracts) were healthy rats, while Group C (n = 5, distilled-water) and Group D (n = 5, cinnamon-extracts) were diabetes-induced rats. Serum lipid profile and HbA1c were measured on D-0 and D-30. FBG, 2-h post-prandial blood glucose, body weight, and food consumption were measured on every fifth day. There was no significant difference in serial blood glucose values in cinnamon-treated group from time 0 (P > 0.05). Following oral glucose, the cinnamon group demonstrated a faster decline in blood glucose compared to controls (P < 0.05). Phase II: Between D0 and D30, the difference in food consumption was shown only in diabetes-induced rats (P < 0.001). Similarly, the significant difference following cinnamon-extracts in FBG and 2-h post-prandial blood glucose from D0 to D30 was shown only in diabetes-induced rats. In cinnamon-extracts administered groups, total and LDL cholesterol levels were lower on D30 in both healthy and diabetes-induced animals (P < 0.001). C. zeylanicum lowered blood glucose, reduced food intake, and improved lipid parameters in diabetes-induced rats.

  16. The synergistic effect of antiglycating agents (MB-92) on inhibition of protein glycation, misfolding and diabetic complications in diabetic-atherosclerotic rat.

    PubMed

    Mahdavifard, S; Bathaie, S Z; Nakhjavani, M; Taghikhani, M

    2016-10-04

    Protein glycation due to hyperglycemia resulting in misfolding and aggregation, which is known as one of the most important reasons of diabetes complications. We previously showed the beneficial effects of some antiglycating agents in diabetic rats. Here, the effect of MB-92, a combination of some amino acids and crocetin (Crt, a saffron carotenoid), was studied in the prevention of diabetic complications in diabetic-atherosclerotic rats. In addition, the inhibitory effect of these treatments on glycation intermediates, aggregation and misfolding of proteins was investigated both in vivo and in vitro. Thus, the streptozotocin-induced diabetic rats that underwent an atherogenic diet were treated with Crt, N-acetylcyctein and MB-92. Then, glycated products and markers of oxidation and inflammation, in addition to other markers of diabetes complications were studied. The results of the in vivo study indicated that the mentioned treatments prevented the atheromatos formation, reduced the increased blood glucose; inhibited the formation of various glycation products, induced glyoxalase system (I and II), diminished oxidation and inflammatory markers, and improved lipid profile and atherosclerotic index in the diabetic-atherosclerotic rats; but MB-92 was the most effective treatment. In vitro results also confirmed that MB-92 was the most effective treatment to inhibit protein glycation and misfolding in comparison with the other treatments. In conclusion, MB-92 showed the greatest potential for inhibition of glycation and oxidation products, atheromatose plaque formation and inflammation in diabetic-atherosclerotic rats, and to control protein glycation, misfolding and aggregation in high glucose concentration; thus, it can be suggested as a new drug to prevent diabetic complications.

  17. Type 2 diabetic rats are sensitive to thioacetamide hepatotoxicity

    SciTech Connect

    Sawant, Sharmilee P.; Dnyanmote, Ankur V.; Warbritton, Alan; Latendresse, John R.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-03-15

    Previously, we reported high hepatotoxic sensitivity of type 2 diabetic (DB) rats to three dissimilar hepatotoxicants. Additional work revealed that a normally nonlethal dose of CCl{sub 4} was lethal in DB rats due to inhibited compensatory tissue repair. The present study was conducted to investigate the importance of compensatory tissue repair in determining the final outcome of hepatotoxicity in diabetes, using another structurally and mechanistically dissimilar hepatotoxicant, thioacetamide (TA), to initiate liver injury. A normally nonlethal dose of TA (300 mg/kg, ip), caused 100% mortality in DB rats. Time course studies (0 to 96 h) showed that in the non-DB rats, liver injury initiated by TA as assessed by plasma alanine or aspartate aminotransferase and hepatic necrosis progressed up to 48 h and regressed to normal at 96 h resulting in 100% survival. In the DB rats, liver injury rapidly progressed resulting in progressively deteriorating liver due to rapidly expanding injury, hepatic failure, and 100% mortality between 24 and 48 h post-TA treatment. Covalent binding of {sup 14}C-TA-derived radiolabel to liver tissue did not differ from that observed in the non-DB rats, indicating similar bioactivation-based initiation of hepatotoxicity. S-phase DNA synthesis measured by [{sup 3}H]-thymidine incorporation, and advancement of cells through the cell division cycle measured by PCNA immunohistochemistry, were substantially inhibited in the DB rats compared to the non-DB rats challenged with TA. Thus, inhibited cell division and compromised tissue repair in the DB rats resulted in progressive expansion of liver injury culminating in mortality. In conclusion, it appears that similar to type 1 diabetes, type 2 diabetes also increases sensitivity to dissimilar hepatotoxicants due to inhibited compensatory tissue repair, suggesting that sensitivity to hepatotoxicity in diabetes occurs in the absence as well as presence of insulin.

  18. Effects of acute diabetes on rat cutaneous wound healing.

    PubMed

    Komesu, Marilena Chinali; Tanga, Marcelo Benetti; Buttros, Kemli Raquel; Nakao, Cristiano

    2004-10-01

    INTRODUCTION:: Diabetes mellitus is a chronic hyperglycaemic disorder. Complicated metabolic mechanisms and increased incidence of infections are clinical hallmarks, mostly associated with its chronicity. There is little information about the early pathological processes in diabetes. The objective of our study was to evaluate the healing process during early phases of experimental diabetes on rat skin. METHODS:: Alloxan induced diabetic rats were used. Non-injected animals were used as control. Punch byopsies on dorsal skin had histopathological evaluation of the healing areas made on days 1, 3 and 7 post-surgery. RESULTS:: The results showed that: (1) in diabetics, the inflammation, the initial healing phase, has a slow beginning and tends to last longer; and (2) diabetic animals showed lower density of neutrophils in healing areas up to 3 days after surgery, and in addition, after day 3, when the neutrophils should leave the healing area, and be replaced by macrophages, compared to controls, diabetic animals showed higher numbers of neutrophils. PRINCIPAL CONCLUSION:: Although diabetes is a chronic progressive disease, acute diabetes can be associated to subclinical alterations, and responsible for deficiencies in defense cells and in repair tissue failures.

  19. [Effect of extracts of Geranium ayavacense W. (Pasuchaca) on glycemia on rats with experimental diabetes mellitus].

    PubMed

    Aranda-Ventura, José; Villacrés, Jorge; Mego, Rosario; Delgado, Henry

    2014-04-01

    To determine if the lyophilized aqueous extract of Geranium ayavacense (Pasuchaca) has any effect on glycemia in rats with experimental diabetes mellitus. Experimental diabetes was induced with alloxan. Rats included in the study met the following criteria: glycemia greater than 200 mg/dL post administration of alloxan, and with a weight greater than 200 g. Rats with experimental diabetes were divided into six groups of eight rats each. Group I received 3 mL of distilled water (control); group II received Geranium ayavacense 12.7 mg/kg; group III received Geranium ayavacense 100 mg/kg; group IV received Geranium ayavacense 200 mg/kg; group V received Geranium ayavacense 300 mg/kg; group VI received Geranium ayavacense 500 mg/kg. Basal glycemia was determined. Glycemia evaluations were performed at the 1st, 3rd, 6th, 12th and 24th hour after administrating the different interventions. Geranium ayavacense groups of 300 and 500 mg/kg decreased glycemia significantly (p <0.01) in every hour assessed after administration of the extract, when compared with the control group. Geranium ayavacense group of 300 mg/kg decreased their blood glucose 8.14; 10.68; 14.87; 19.36 and 23.7% in the 1st, 3rd, 6th, 12th and 24th hour respectively. Under experimental conditions, the aqueous extract of Geranium ayavacense has hypoglycemic effects in rats.

  20. Topical erythropoietin promotes wound repair in diabetic rats.

    PubMed

    Hamed, Saher; Ullmann, Yehuda; Masoud, Muhannad; Hellou, Elias; Khamaysi, Ziad; Teot, Luc

    2010-01-01

    Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds.

  1. Sweet taste and diet in type II diabetes.

    PubMed

    Tepper, B J; Hartfiel, L M; Schneider, S H

    1996-07-01

    The relationship between sweet taste function and dietary intake was studied in 21 patients with type II diabetes mellitus and 16 age-, weight-, and sex-matched controls. Subjects rated the sweetness intensity and pleasantness of a series of beverage samples sweetened with sucrose: 1.5-24%, fructose: 1-18%, or aspartame: 0.25-4%. They also kept 7-day food records. No group differences were found in sweet taste perception, pleasantness ratings, daily energy intakes, or macronutrient composition of the diets. However, subjects with diabetes consumed less sucrose but 3.5 times more alternative sweeteners than did controls. Peak pleasantness ratings for the beverage samples were positively correlated with dietary sweetness content in the subjects with diabetes but not the controls. These findings suggest that in diabetes, hedonic ratings for a sweetened beverage were related to dietary sweetness intake rather than changes in sweet taste perception.

  2. Chlorogenic acid decreases retinal vascular hyperpermeability in diabetic rat model.

    PubMed

    Shin, Joo Young; Sohn, Joonhong; Park, Kyu Hyung

    2013-04-01

    To evaluate the effect of chlorogenic acid (CGA), a polyphenol abundant in coffee, on retinal vascular leakage in the rat model of diabetic retinopathy, Sprague-Dawley rats were divided into four groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with 10 and 20 mg/kg chlorogenic acid intraperitoneally daily for 14 days, respectively. Blood-retinal barrier (BRB) breakdown was evaluated using FITC-dextran. Vascular endothelial growth factor (VEGF) distribution and expression level was evaluated with immunohistochemistry and Western blot analysis. Expression of tight junction proteins, occludin and claudin-5, and zonula occludens protein, ZO-1 was also evaluated with immunohistochemistry and Western blot analysis. BRB breakdown and increased vascular leakage was found in diabetic rats, with increased VEGF expression and down-regulation of occludin, claudin-5, and ZO-1. CGA treatment effectively preserved the expression of occludin, and decreased VEGF levels, leading to less BRB breakdown and less vascular leakage. CGA may have a preventive role in BRB breakdown in diabetic retinopathy by preserving tight junction protein levels and low VEGF levels.

  3. Berberine attenuates intestinal disaccharidases in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Li; Deng, Yuanxiong; Yu, Sen; Lu, Shousi; Xie, Lin; Liu, Xiaodong

    2008-05-01

    Previous studies demonstrated anti-diabetic effects of berberine. However, the facts that berberine had low bioavailability and poor absorption through the gut wall indicated that berberine might exert its antihyperglycaemic effect in the intestinal tract before absorption. The purpose of this study was to investigate whether berberine attenuates disaccharidase activities and beta-glucuronidase activity in the small intestine of streptozotocin (STZ)-induced diabetic rats. Two groups of STZ-induced diabetic rats were treated with protamine zinc insulin (10 U/Kg) subcutaneously twice daily and berberine (100 mg/Kg) orally once daily for 4 weeks, respectively. Both age-matched normal rats and diabetic control rats received physiological saline only. Fasting blood glucose levels, body weight, intestinal disaccharidase and beta-glucuronidase activities in duodenum, jejunum and ileum were assessed for changes. Our findings suggested that berberine treatment significantly decreases the activities of intestinal disaccharidases and beta-glucuronidase in STZ-induced diabetic rats. The results demonstrated that the inhibitory effect on intestinal disaccharidases and beta-glucuronidase of berberine might be one of the mechanisms for berberine as an antihyperglycaemic agent.

  4. Expression of aquaporins in the retina of diabetic rats.

    PubMed

    Hollborn, Margrit; Dukic-Stefanovic, Sladjana; Pannicke, Thomas; Ulbricht, Elke; Reichenbach, Andreas; Wiedemann, Peter; Bringmann, Andreas; Kohen, Leon

    2011-09-01

    The development of retinal edema is the main reason of impaired vision in non-proliferative diabetic retinopathy. Water transport through aquaporins (AQPs) has been suggested to facilitate the development of ischemic edema in the retina. Here, we investigated whether experimental diabetic retinopathy in rats results in alterations of the AQP expression in the neural retina and retinal pigment epithelium (RPE). Experimental diabetes in rats was induced by a single intravenous injection of streptozotocin (65 mg/kg body weight). The gene expression of AQPs in tissues from control and diabetic rats was examined by real-time RT-PCR. Retinal cryosections were immunostained against AQP5, 6, and 9. The total RNAs extracted from the neural retina and RPE contained gene transcripts for AQP0, 1, 3, 4, 5, 6, 8, 9, 11, and 12. Experimental diabetes was associated with an upregulation of AQP1 in the neural retina, and of AQP5, 9, 11, and 12 in the RPE. Furthermore, diabetes was associated with a downregulation of AQP6 and AQP11 in the neural retina, and of AQP0 in the RPE. AQP5 and AQP9 immunolabelings of the RPE were increased, and AQP6 labeling of the outer plexiform layer was decreased in retinal slices from diabetic rats in comparison to slices from control rats. The data suggest that experimental diabetic retinopathy is associated with a complex pattern of alteration in the retinal AQP expression. These alterations might be involved in the adaptation of retinal cells to hyperglycemic conditions and the development and/or resolution of retinal edema.

  5. Electrophysiological changes in optic neuropathy of streptozotocin induced diabetic rats

    PubMed Central

    Ghita, AM; Parvu, D; Sava, R; Georgescu, L; Zagrean, L

    2013-01-01

    The visually evoked potentials are electrical signals generated by the occipital cortex due to electrical stimulus. The clinical importance of VEP is to diagnose the functional changes of the optic nerve in different diseases such as diabetic mellitus. Our study sought latency of VEP changes depending on glycemic value and duration of diabetes in Wistar rats. Methods: this study evaluated the VEP of 25 rats in three groups: control group, diabetic group 1 with glycemic values between 200-400mg/dl and diabetic group 2 with glycemic values between 400 and 600mg/dl. These rats from diabetic group 2 were followed for 4 months and the ones in control group and diabetic group 1 for 5 months. Results: the latency of VEP shows slight changes without any statistical significance in the control group. In diabetic group 1 and 2 similar changes occurred, with statistical significance and the amplitude of the changes was proportional with the glycemic value. The rats had a rapid increase of VEP latency after the induction of diabetes and returned to a normal range in the first month. After a time, when the latencies of VEP were in normal range, a new growth appeared faster and larger as the glycemic values were higher. Conclusion: diabetes brings changes to the visual signal transmission and to the central processing, this being revealed by the examination of the visually evoked potential. Increased VEP latency is statistically correlated with the changes that occur at the level of the values of glucose in blood. A rapid growth in blood sugar lowers the visual signal transmission. This change is temporary despite the persistence of elevated blood glucose values, probably by adjusting to the new condition. However, maintaining high glycemic values remotely produces a progressive increase of the delay of the visual signal. This progressive increase is faster as blood glucose levels are higher. PMID:24155786

  6. Hypoglycemic and hypolipidemic effects of methanol seed extract of Citrus paradisi Macfad (Rutaceae) in alloxan-induced diabetic Wistar rats.

    PubMed

    Adeneye, A A

    2008-01-01

    Alcohol decoction of Citrus paradisi Macfad (Rutaceae) seed is reputed for the local management of array of human diseases including, anemia, diabetes mellitus and obesity by some Yoruba herbalists (SouthWest, Nigeria). Despite its historic use, scientific evaluation of its folkloric use in the management of diabetes mellitus is scarce. The present study was designed at investigating the glucose and lipid lowering effects of methanol seed extract of Citrus paradisi Macfad (MECP) in alloxan-induced diabetic rats. In addition, the phytochemical analysis of the extract was also conducted using standard procedures. Young adult, male, alloxan-induced diabetic rats were randomly divided into groups I - VI with 12 rats in each group. Group I rats were the normal untreated rats while group II rats served as the diabetic untreated rats while Rats in groups III - VI served as diabetic rats treated with 100, 300 and 600 mg/kg/day MECP and 20 mg/kg/ day metformin, respectively, for 30 days. On the 15th and respectively, 31st day, blood samples from the fasted rats were obtained for fasting plasma glucose (FPG), plasma triglycerides (TG), total cholesterol (TC), high density lipoprotein- cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c) and very low density lipoprotein-cholesterol (VLDL-c) from the sacrificed rats. Oral treatment with 100 - 600 mg/kg/day MECP, for 30 days, resulted in significant (p < 0.05, p < 0.01, p < 0.001) reductions in FPG, TG, TC, LDL-c, VLDL-c in the diabetic rats, effects which were comparable to that of metformin. The extract also caused significant (p < 0.05, p < 0.01) rise in HDL-c values in the alloxan diabetic rats. Phytochemical result showed the presence of alkaloids, flavonoids, cardiac glycosides, tannins and saponin in varying concentrations. The biological effects recorded for the extract could be due to any or a combination of these phytochemical constituents. Results of this study lend support to the traditional use of

  7. Topical effects of nebivolol on wounds in diabetic rats.

    PubMed

    Gulcan, Erim; Kuçuk, Ayşegul; Çayci, Kasim; Tosun, Murat; Emre, Habib; Koral, Lokman; Aktan, Yasemin; Avsar, Umit

    2012-09-29

    Recently, it has reported that nebivolol might be useful in the treatment of diabetes mellitus foot ulcers. The aim of this study was to examine treatment of the wounds in streptozotocin-induced diabetic rats with topical nebivolol. Two 15 × 15 mm-sized wounds were created in 56 streptozotocin-induced rats. A total of 56 diabetic wounds were studied in eight groups (n=7). No treatment was administered to the first and second groups. The third and fourth groups consisted of diabetic rats that were administered 1:1 mixture of lanolin and vaseline for 7 and 14 days, respectively. Five percent nebivolol plus 1:1 mixture of lanolin and vaseline was administered to rats in the fifth and sixth groups for 7 and 14 days, respectively, and 10% nebivolol plus 1:1 mixture of lanolin and vaseline was administered to rats in the seventh and eighth groups for 7 and 14 days, respectively. On days 7 and 14, wound healing was observed, and the percent of wound healing was determined by measuring its size and histopathologic examination. The ratio was calculated by the formula, healing ratio (%)=100 ×(1-wound area/initial wound area). Statistical analysis was performed by ANOVA with Tukey's HSD test and Mann-Whitney U test, using SPSS 15.0 software. On days 7 and 14, rates of wound healing in the fifth, sixth, seventh, and eighth groups were 57.42%, 89.16%, 60.80%, and 91.80%, respectively. Multiple comparison showed that rates of wound healing were significantly higher in rats administered 5% and 10% nebivolol than those in rats administered a mixture of lanolin and vaseline and in the untreated group (P<0.05). Topical nebivolol therapy may be useful for wound healing in diabetic rats. Further studies are needed to support these data. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Explorative study on diabetes neuropathy among type II diabetic patients in Universiti Sains Malaysia Hospital.

    PubMed

    Abougalambou, Salwa Selim Ibrahim; Abougalambou, Ayman Selim

    2012-01-01

    The aim of this study was to determine risk factors and prevalence of diabetic neuropathy (DN) among type II diabetic patients in Malaysian hospital setting. a observational prospective longitudinal follow up study design was selected, total no of respondents were 1077 type 2 diabetes mellitus outpatients recruited via attended the diabetes clinics at Hospital Universiti Sains Malaysia (HUSM) in Kelantan. The diagnosis of neuropathy was confirmed by nerve conduction studies. Logistic regression analysis was used to assess the independent variables that affect the development of neuropathy. The prevalence of nephropathy is 54.3%. Longitudinal logistic regression identified four predictive variables on the development and progression of diabetic neuropathy that are: duration of diabetes, retinopathy, HbA1c at second visit, and creatinine clearance third visit. Findings of this study show high prevalence of diabetic neuropathy. HbA1c and creatinine clearance are two modifiable risk factors for the development of diabetic neuropathy. Copyright © 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  9. Danhong Huayu Koufuye combined with metformin attenuated diabetic retinopathy in Zucker diabetic fatty rats

    PubMed Central

    Chen, Wen-Pei; Wang, Yan-Dong; Ma, Yan; Zhang, Zi-Yang; Hu, Lu-Yun; Lin, Jun-Li; Lin, Bao-Qin

    2015-01-01

    AIM To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type-2 diabetes, and then to investigate the mechanisms. METHODS ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism. PMID:26682154

  10. Enhanced nitric oxide generation from nitric oxide synthases as the cause of increased peroxynitrite formation during acute restraint stress: Effects on carotid responsiveness to angiotensinergic stimuli in type-1 diabetic rats.

    PubMed

    Moreira, Josimar D; Pernomian, Larissa; Gomes, Mayara S; Moreira, Rafael P; do Prado, Alejandro F; da Silva, Carlos H T P; de Oliveira, Ana M

    2016-07-15

    Diabetes mellitus is associated with reactive oxygen and nitrogen species accumulation. Behavioral stress increases nitric oxide production, which may trigger a massive impact on vascular cells and accelerate cardiovascular complications under oxidative stress conditions such as Diabetes. For this study, type-1 Diabetes mellitus was induced in Wistar rats by intraperitoneal injection of streptozotocin. After 28 days, cumulative concentration-response curves for angiotensin II were obtained in endothelium-intact carotid rings from diabetic rats that underwent to acute restraint stress for 3h. The contractile response evoked by angiotensin II was increased in carotid arteries from diabetic rats. Acute restraint stress did not alter angiotensin II-induced contraction in carotid arteries from normoglycaemic rats. However acute stress combined with Diabetes increased angiotensin II-induced contraction in carotid rings. Western blot experiments and the inhibition of nitric oxide synthases in functional assays showed that neuronal, endothelial and inducible nitric oxide synthase isoforms contribute to the increased formation of peroxynitrite and contractile hyperreactivity to angiotensin II in carotid rings from stressed diabetic rats. In summary, these findings suggest that the increased superoxide anion generation in carotid arteries from diabetic rats associated to the increased local nitric oxide synthases expression and activity induced by acute restrain stress were responsible for exacerbating the local formation of peroxynitrite and the contraction induced by angiotensin II. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Metabolomic analysis of rat serum in streptozotocin-induced diabetes and after treatment with oral triethylenetetramine (TETA)

    PubMed Central

    2012-01-01

    Background The prevalence, and associated healthcare burden, of diabetes mellitus is increasing worldwide. Mortality and morbidity are associated with diabetic complications in multiple organs and tissues, including the eye, kidney and cardiovascular system, and new therapeutics to treat these complications are required urgently. Triethylenetetramine (TETA) is one such experimental therapeutic that acts to chelate excess copper (II) in diabetic tissues and reduce oxidative stress and cellular damage. Methods Here we have performed two independent metabolomic studies of serum to assess the suitability of the streptozotocin (STZ)-induced rat model for studying diabetes and to define metabolite-related changes associated with TETA treatment. Ultraperformance liquid chromatography-mass spectrometry studies of serum from non-diabetic/untreated, non-diabetic/TETA-treated, STZ-induced diabetic/untreated and STZ-induced diabetic/TETA-treated rats were performed followed by univariate and multivariate analysis of data. Results Multiple metabolic changes related to STZ-induced diabetes, some of which have been reported previously in other animal and human studies, were observed, including changes in amino acid, fatty acid, glycerophospholipid and bile acid metabolism. Correlation analysis suggested that treatment with TETA led to a reversal of diabetes-associated changes in bile acid, fatty acid, steroid, sphingolipid and glycerophospholipid metabolism and proteolysis. Conclusions Metabolomic studies have shown that the STZ-induced rat model of diabetes is an appropriate model system to undertake research into diabetes and potential therapies as several metabolic changes observed in humans and other animal models were also observed in this study. Metabolomics has also identified several biological processes and metabolic pathways implicated in diabetic complications and reversed following treatment with the experimental therapeutic TETA. PMID:22546713

  12. Role of AT1 receptors in permeability of the blood-brain barrier in diabetic hypertensive rats.

    PubMed

    Awad, Azza S

    2006-09-01

    The precise mechanisms of vascular diseases in patients with diabetic hypertensive are not clearly understood. There are evidences of alteration in permeability of blood-brain barrier (BBB) in diabetic hypertensive rats. This study sought to examine the effect of candesartan on the systolic blood pressure and the brain endothelial barrier function and antioxidant enzymes in rat brain. Five groups of eight male Sprague-Dawley rats include: control group (gpI), diabetic hypertensive group (gpII), diabetic hypertensive group treated with candesartan (gpIII), diabetic hypertensive rats with epinephrine (gpIV) and diabetic hypertensive rats with epinephrine treated with candesartan (gpV). Diabetes was induced by single injection of 55 mg kg(-1) streptozotocin (STZ) i.p. Blood glucose was measured, rats with blood glucose higher than 300 mg/dl were identified as diabetic. After induction of diabetes, rats received L-NAME (0.5 mg/ml in drinking water for 1 week) starting on the day 4 after STZ injection. Systolic blood pressure (SBP) was recorded two times, at day 0 (before starting L-NAME) and at day 7 (after L-NAME treatment). Also, body weight was measured two times, at initial time (before STZ injection) and terminal (at the last day in the experiment). On the day of acute experiment, rats were anesthetized with sodium pentobarbital (35 mg/kg, i.p.). The integrity of the BBB was investigated using Evans blue (EB) dye (4 ml/kg, 2%). Epinephrine was used (40 micro g/kg) to increase the permeability of the brain. After decapitation, first the brain was removed, next homogenized and then the content of EB dye in the brain was measured. Another five groups of rats manipulated with the same manner except EB dye injection. These second group to evaluate antioxidant enzymes, reduced glutathione (GSH), lipid peroxides and superoxide dismutase (SOD) in brain homogenate. This study indicates that, in diabetic hypertensive rats, epinephrine administration leads to increase in

  13. Berberine chloride improved synaptic plasticity in STZ induced diabetic rats.

    PubMed

    Moghaddam, Hamid Kalalian; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Goshadrou, Fatemeh; Ronaghi, Abdolaziz

    2013-09-01

    Previous studies indicated that diabetes affects synaptic transmission in the hippocampus, leading to impairments of synaptic plasticity and defects in learning and memory. Although berberine treatment ameliorates memory impairment and improves synaptic plasticity in streptozotocin (STZ) induced diabetic rats, it is not clear if the effects are pre- or post-synaptic or both. The aim of this study was to evaluate the effects of berberine chloride on short-term plasticity in inhibitory interneurons in the dentate gyrus of STZ-induced diabetic rats. Experimental groups included: The control, control berberine treated (100 mg/kg), diabetic and diabetic berberine treated (50,100 mg/kg/day for 12 weeks) groups. The paired pulse paradigm was used to stimulate the perforant pathway and field excitatory post-synaptic potentials (fEPSP) were recorded in dentate gyrus (DG). In comparison with control, paired pulse facilitation in the diabetic group was significantly increased (P < 0.01) and this effect prevented by chronic berberine treatment (50,100 mg/kg). However, there were no differences between responses of the control berberine 100 mg/kg treated and diabetes berberine treated (50 and 100 mg/kg) groups as compared to the control group. The present results suggest that the pre-synaptic component of synaptic plasticity in the dentate gyrus is affected under diabetic conditions and that berberine prevents this effect.

  14. Intracavernous Injection of Human Umbilical Cord Blood Mononuclear Cells Improves Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Cengiz, Tugba; Kaya, Ecem; Oral, Didem Yilmaz; Ozakca, Isil; Bayatli, Nur; Karabay, Arzu Zeynep; Ensari, Tugba Altun; Karahan, Tuna; Yilmaz, Enis; Gur, Serap

    2017-01-01

    Erectile dysfunction (ED) worsens in men with diabetes. Human umbilical cord blood (HUCB), because of its widespread availability and low immunogenicity, is a valuable source for stem cell-based therapies. To determine the effect of intracavernous injection of HUCB mononuclear cells (MNCs) on ED in rats with diabetes induced by streptozotocin. Thirty adult male Sprague-Dawley rats were equally divided into three groups: (i) control, (ii) diabetes induced by streptozotocin (35 mg/kg intravenously for 8 weeks), and (iii) diabetic rats treated with MNCs (1 × 10(6) cells by intracavernosal injection). The HUCB-MNCs isolated by the Ficoll-Hypaque technique were obtained from eight healthy donors and administered to diabetic rats after 4 weeks. The ratio of intracavernosal pressure to mean arterial pressure ratio; the protein expression of endothelial and neuronal markers, such as von Willebrand factor, neuronal nitric oxide synthase, hypoxia-inducible factor-1α, and vascular endothelium growth factor; and the relative area of smooth muscle to collagen using western blotting and Masson trichrome staining were determined. Diabetic rats demonstrated a significantly decreased ratio of intracavernosal pressure to mean arterial pressure (0.26 ± 0.04; P < .01) and treatment with MNCs restored erectile function in diabetic rats (0.67 ± 0.05) compared with control rats (0.56 ± 0.02). In bath studies, neurogenic relaxant and contractile responses were significantly decreased in diabetic cavernosal tissues, which were restored by treatment. The ratio of smooth muscle to collagen was partly recovered by treatment, whereas von Willebrand factor levels were not altered in any group. Neuronal nitric oxide synthase and vascular endothelium growth factor levels were decreased, which were not restored by treatment. Increased hypoxia-inducible factor-1α protein expression in the diabetic group was completely normalized in MNC-treated diabetic samples. These results suggest that

  15. Protein turnover in adipose tissue from fasted or diabetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.; Ost, Alan H.; Coffman, Julia

    1986-01-01

    Protein synthesis and degradation in vitro were compared in epididymal fat pads from animals deprived of food for 48 h or treated 6 or 12 days prior with streptozotocin to induce diabetes. Although both fasting and diabetes led to depressed (-24 to -57 percent) protein synthesis, the diminution in protein degradation (-63 to -72 percent) was even greater, so that net in vitro protein balance improved dramatically. Insulin failed to inhibit protein degradation in fat pads of these rats as it does for fed animals. Although insulin stimulated protein synthesis in fat pads of fasted and 12 day diabetic rats, the absolute change was much smaller than that seen in the fed state. The inhibition of protein degradation by leucine also seems to be less in fasted animals, probably because leucine catabolism is slower in fasting. These results show that fasting and diabetes may improve protein balance in adipose tissue but diminish the regulatory effects of insulin.

  16. Protein turnover in adipose tissue from fasted or diabetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.; Ost, Alan H.; Coffman, Julia

    1986-01-01

    Protein synthesis and degradation in vitro were compared in epididymal fat pads from animals deprived of food for 48 h or treated 6 or 12 days prior with streptozotocin to induce diabetes. Although both fasting and diabetes led to depressed (-24 to -57 percent) protein synthesis, the diminution in protein degradation (-63 to -72 percent) was even greater, so that net in vitro protein balance improved dramatically. Insulin failed to inhibit protein degradation in fat pads of these rats as it does for fed animals. Although insulin stimulated protein synthesis in fat pads of fasted and 12 day diabetic rats, the absolute change was much smaller than that seen in the fed state. The inhibition of protein degradation by leucine also seems to be less in fasted animals, probably because leucine catabolism is slower in fasting. These results show that fasting and diabetes may improve protein balance in adipose tissue but diminish the regulatory effects of insulin.

  17. Attenuation of Diabetic Conditions by Sida rhombifolia in Moderately Diabetic Rats and Inability to Produce Similar Effects in Severely Diabetic in Rats

    PubMed Central

    Chaturvedi, Padmaja; Kwape, Tebogo Elvis

    2015-01-01

    Objectives: This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. Methods: SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). Results: OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. Conclusion: The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes. PMID:26998385

  18. Attenuation of Diabetic Conditions by Sida rhombifolia in Moderately Diabetic Rats and Inability to Produce Similar Effects in Severely Diabetic in Rats.

    PubMed

    Chaturvedi, Padmaja; Kwape, Tebogo Elvis

    2015-12-01

    This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes.

  19. Combination therapy with losartan and L-carnitine protects against endothelial dysfunction of streptozotocin-induced diabetic rats.

    PubMed

    Sleem, Mostafa; Taye, Ashraf; El-Moselhy, Mohamed A; Mangoura, Safwat A

    2014-12-05

    Endothelial dysfunction is a critical factor during the initiation of diabetic cardiovascular complications and angiotensin II appears to play a pivotal role in this setting. The present study aimed to investigate whether the combination therapy with losartan and the nutritional supplement, L-carnitine can provide an additional protection against diabetes-associated endothelial dysfunction and elucidate the possible mechanism(s) underlying this effect. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) in rat. Effects of losartan (20 mg/kg, orally, 3 months) and L-carnitine (200 mg/kg, orally, 3 months) on tumor necrosis factor (TNF)-α, oxidative stress parameters, endothelial nitric oxide synthase expression (eNOS), and vascular function were evaluated. Our results showed a marked increase in aortic superoxide anion (O2(-)) production and serum malondialdehyde (MDA) level alongside attenuating antioxidant enzyme capacities in diabetic rats. This was associated with a significant increase in anigiotensin II type 1 receptor gene expression and TNF-α serum level of diabetic rats alongside reducing aortic eNOS gene expression and nitric oxide (NO) bioavailability. The single or combined administration of losartan and L-carnitine significantly inhibited these changes. Additionally, the vascular endothelium-dependent relaxation with acetylcholine (ACh) in aortic diabetic rat was significantly ameliorated by the single and combined administration of losartan or L-carnitine. Noteworthy, the combination therapy exhibited a more profound response over the monotherapy. Collectively, our results demonstrate that the combined therapy of losartan and L-carnitine affords additive beneficial effects against diabetes-associated endothelial dysfunction, possibly via normalizing the dysregulated eNOS and reducing the inflammation and oxidative stress in diabetic rats.

  20. Advanced glycation end products and diabetic nephropathy: a comparative study using diabetic and normal rats with methylglyoxal-induced glycation.

    PubMed

    Rodrigues, Lisa; Matafome, Paulo; Crisóstomo, Joana; Santos-Silva, Daniela; Sena, Cristina; Pereira, Paulo; Seiça, Raquel

    2014-03-01

    Hyperglycemia-related advanced glycation end product (AGE) formation is a key mechanism in diabetic nephropathy. Since methylglyoxal (MG) is a potent AGE precursor, we aimed to assess the role of MG-related AGE formation in the progression of renal damages. A comparative study between Wistar (W, normal) and Goto-Kakizaki (GK, nonobese type 2 diabetic) rats was performed at 6 and 14 months old and after 14 weeks of MG administration to 6-month-old rats. Diabetic rats showed progressive structural, biochemical, and functional alterations, including AGE, albuminuria, and tissue hypoxia, which were partially mimicked by MG administration to young GK rats. Aged Wistar rats had an impairment of some parameters, whereas MG administration caused a phenotype similar to young GK rats, including oxidative stress, impaired apoptotic and angiogenic markers, and structural lesions. MG accumulation specifically impaired several of the renal disease markers progressively observed in diabetic rats, and thus, it contributes to the progression of diabetic nephropathy.

  1. Hypoglycaemic effect of galactooligosaccharides in alloxan-induced diabetic rats.

    PubMed

    Sangwan, Vikas; Tomar, Sudhir K; Ali, Babar; Singh, Ram R B; Singh, Ashish K

    2015-02-01

    This study was conducted to assess the effect of prebiotic galactooligosaccharides (GOS) on alloxan-induced diabetes in male Sprague-Dawley (SD) rats. Diabetes was induced by administration of alloxan (100 mg/kg) and rats were divided in 4 groups: normal control group (NCG), prebiotic control group (PCG), diabetic control group (DCG) and diabetic prebiotic group (DPG). While PCG and DPG were fed with GOS supplemented (10% w/w) diet, NCG and DCG were administered with basal diet. Rats were sacrificed after 42 d for collection of blood and liver. Faecal samples were collected at the interval of 7 d throughout the study for measurement of lactobacilli and coliform count. Feeding of GOS decreased or delayed the severity of diabetes by amelioration of diabetes associated markers including fasting blood glucose, haemoglobin, glycosylated haemoglobin triglycerides, total cholesterol, low density lipoproteins, creatinine and urea. GOS was also found to improve the levels of antioxidative enzymes (superoxide dismutase, catalase and glutathione peroxidase) in liver and blood. Improvement in lactobacilli count along with a concomitant decrease in coliform count was observed in GOS fed groups.

  2. Diabetes-induced changes in specific lipid molecular species in rat myocardium.

    PubMed Central

    Han, X; Abendschein, D R; Kelley, J G; Gross, R W

    2000-01-01

    Intrinsic cardiac dysfunction during the diabetic state has been causally linked to changes in myocardial lipid metabolism. However, the precise alterations in the molecular species of myocardial polar and non-polar lipids during the diabetic state and their responses to insulin have not been investigated. Herein we demonstrate four specific alterations in rat myocardial lipid molecular species after induction of the diabetic state by streptozotocin treatment: (i) a massive remodelling of triacylglycerol molecular species including a >5-fold increase in tripalmitin mass and a 60% decrease in polyunsaturated triacylglycerol molecular species mass (i.e. triacylglycerols containing at least one acyl residue with more than two double bonds); (ii) a 46% increase in myocardial phosphatidylinositol mass; (iii) a 44% increase in myocardial plasmenylethanolamine mass and (iv) a 22% decrease in 1-stearoyl-2-arachidonoyl phosphatidylethanolamine content. Each of the changes in phospholipid classes, subclasses and individual molecular species were prevented by insulin treatment after induction of the diabetic state. In sharp contrast, the alterations in triacylglycerol molecular species were not preventable by peripheral insulin treatment after induction of the diabetic state. These results segregate diabetes-induced alterations in myocardial lipid metabolism into changes that can be remedied or not by routine peripheral insulin treatment and suggest that peripheral insulin therapy alone may not be sufficient to correct all of the metabolic alterations present in diabetic myocardium. PMID:11062060

  3. Antihyperalgesic Activity of Rhodiola rosea in a Diabetic Rat Model.

    PubMed

    Déciga-Campos, Myrna; González-Trujano, Maria Eva; Ventura-Martínez, Rosa; Montiel-Ruiz, Rosa Mariana; Ángeles-López, Guadalupe Esther; Brindis, Fernando

    2016-02-01

    Preclinical Research Rhodiola rosea L. (Crassulaceae) is used for enhancing physical and mental performance. Recent studies demonstrated that R. rosea had anti-inflammatory activity in animal models, for example, carrageenan- and nystatin-induced edema in rats, possibly by inhibiting phospholipase A2 and cyclooxygenases-1 and -2. In addition, R. rosea had antinociceptive activity in thermal and chemical pain tests as well as mechanical hyperalgesia. The purpose of the present study was to assess the antihyperalgesic effect of an ethanol extract of Rhodiola rosea (R. rosea) in a diabetic rat model. Rats were administered a single dose of streptozotocin (STZ; 50 mg/kg, i.p.) and hyperalgesia was evaluated four weeks later. Formalin-evoked (0.5%) flinching was increased in diabetic rats compared with nondiabetic controls Systemic (1-100 mg/kg, i.p.) and local (0.1-10 mg/paw into the dorsal surface of the right hind paw) administration of R. rosea ethanol extract dose-dependently reduced formalin-induced hyperalgesia in diabetic rats. The antihyperalgesic effect of R. rosea was compared with gabapentin. These results suggest that R. rosea ethanol extract may have potential as a treatment for diabetic hyperalgesia. © 2016 Wiley Periodicals, Inc.

  4. Acute exercise adjustments of cardiovascular autonomic control in diabetic rats.

    PubMed

    Da Pureza, Demilto Yamagushi; Jorge, Luciana; Sanches, Iris Callado; Irigoyen, Maria-Cláudia; De Souza, Romeu Rodrigues; De Angelis, Kátia

    2012-07-01

    We evaluated the role of cardiovascular autonomic changes in hemodynamics at rest and in response to exercise in streptozotocin-induced diabetic rats. Male Wistar rats were divided into nondiabetic (ND, n = 8) and diabetic (D, n = 8) groups. Arterial pressure signals were recorded in the basal state and after atropine or propranolol injections at rest, during exercise and during recovery. At rest, vagal tonus was reduced in D (37 ± 3 bpm) in comparison with the ND group (61 ± 9 bpm). Heart rate during exercise was lower in D in relation to ND rats associated with reduced vagal withdrawal in the D group. The D rats had an increase in vagal tonus in the recovery period (49 ± 6 bpm). Exercise-induced hemodynamic adjustment impairment in diabetic rats was associated with reduced cardiac vagal control. The vagal dysfunction was attenuated after aerobic exercise, reinforcing the positive role of this approach in the management of cardiovascular risk in diabetics. Copyright © 2012 Wiley Periodicals, Inc.

  5. Rice endosperm protein slows progression of fatty liver and diabetic nephropathy in Zucker diabetic fatty rats.

    PubMed

    Kubota, Masatoshi; Watanabe, Reiko; Yamaguchi, Miki; Hosojima, Michihiro; Saito, Akihiko; Fujii, Mikio; Fujimura, Shinobu; Kadowaki, Motoni

    2016-10-01

    We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period. Hepatic lipids and metabolites were measured and renal glomeruli were observed morphologically. HbA1c levels were significantly lower in rats fed REP, compared with C (P<0·05). Compared with C in the liver, REP prevented lipid accumulation (total lipid, TAG and total cholesterol, P<0·01). Liver metabolome analysis indicated that levels of metabolites associated with glycolysis, the pentose phosphate pathway and carnitine metabolism were significantly greater in the REP group than in the C group (P<0·05), suggesting activation of both glucose catabolism and fatty acid oxidation. The metabolite increases promoted by REP may contribute to suppression of liver lipid accumulation. Urinary excretion of albumin and N-acetyl-β-d-glucosaminidase was significantly reduced in rats fed REP for 8 weeks (P<0·01). In addition, there was a distinct suppression of mesangial matrix expansion and glomerular hypertrophy in response to REP (P<0·01). Thus, REP had preventive effects on obese diabetes, fatty liver and diabetic nephropathy.

  6. Microarray analysis of thioacetamide-treated type 1 diabetic rats

    SciTech Connect

    Devi, Sachin S.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-04-01

    It is well known that diabetes imparts high sensitivity to numerous hepatotoxicants. Previously, we have shown that a normally non-lethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats due to inhibited tissue repair allowing progression of liver injury. On the other hand, DB rats exposed to 30 mg TA/kg exhibit delayed tissue repair and delayed recovery from injury. The objective of this study was to investigate the mechanism of impaired tissue repair and progression of liver injury in TA-treated DB rats by using cDNA microarray. Gene expression pattern was examined at 0, 6, and 12 h after TA challenge, and selected mechanistic leads from microarray experiments were confirmed by real-time RT-PCR and further investigated at protein level over the time course of 0 to 36 h after TA treatment. Diabetic condition itself increased gene expression of proteases and decreased gene expression of protease inhibitors. Administration of 300 mg TA/kg to DB rats further elevated gene expression of proteases and suppressed gene expression of protease inhibitors, explaining progression of liver injury in DB rats after TA treatment. Inhibited expression of genes involved in cell division cycle (cyclin D1, IGFBP-1, ras, E2F) was observed after exposure of DB rats to 300 mg TA/kg, explaining inhibited tissue repair in these rats. On the other hand, DB rats receiving 30 mg TA/kg exhibit delayed expression of genes involved in cell division cycle, explaining delayed tissue repair in these rats. In conclusion, impaired cyclin D1 signaling along with increased proteases and decreased protease inhibitors may explain impaired tissue repair that leads to progression of liver injury initiated by TA in DB rats.

  7. Long-term effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki rat.

    PubMed

    Howarth, Frank C; Jacobson, Michael; Shafiullah, Mohamed; Adeghate, Ernest

    2008-03-01

    In vivo biotelemetry studies have demonstrated a variety of heart rhythm disturbances in type 1 diabetes mellitus. In the streptozotocin (STZ)-induced diabetic rat, these disturbances have included reductions in heart rate (HR) and heart rate variability (HRV) and an electrocardiogram that displays prolonged QRS duration and Q-T interval. The aim of this study was to investigate the chronic effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki (GK) rat. Transmitter devices were surgically implanted in the peritoneal cavity of young male GK and age-matched Wistar control rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. Electrocardiogram, physical activity and body temperature data were recorded in rats from age 2 to 15 months. Data were acquired for 2 weeks each month. Non-fasting blood glucose, glucose tolerance and body weight were measured periodically. In GK rats, growth rate and maximal attained body weight were significantly reduced and non-fasting blood glucose was progressively increased compared with age-matched Wistar control animals. Heart rate was significantly lower in GK compared with control rats at 2, 7 and 15 months of age. At 2 months of age, HR was 316 +/- 6 beats min(-1) in GK rats compared with 370 +/- 7 beats min(-1) in Wistar control animals. There was a progressive age-dependent decline in HRV in Wistar control rats; however, HRV in GK rats did not alter significantly with age. Heart rate variability was significantly reduced in GK compared with Wistar control rats at 2 and 7 months. At 2 months of age, HRV was 28 +/- 2 beats min(-1) in GK rats compared with 38 +/- 3 beats min(-1) in Wistar control rats. Reduced HR in GK rats may be an inherited characteristic. The absence of age-dependent reductions in HRV in GK rats may be a consequence of an underlying impairment of autonomic control which manifests at early age.

  8. Losartan reduces oxidative damage to renal DNA and conserves plasma antioxidant capacity in diabetic rats.

    PubMed

    Lodovici, Maura; Bigagli, Elisabetta; Tarantini, Francesca; Di Serio, Claudia; Raimondi, Laura

    2015-11-01

    Increased reactive oxygen species (ROS) levels produced by hyperglycemia and angiotensin-II (AT-II) are considered among the pathogenic factors in the malignant transformation of diabetic renal cells. We aimed to investigate the potential role of AT-II in the increased cancer risk seen in diabetes; measuring oxidative damage to renal DNA and protective antioxidant defenses, including adiponectin (Adp) and plasma antioxidant capacity by the Ferric Reducing Ability of Plasma (FRAP) method. In the kidney of streptozotocin (STZ)-induced (55 mg/kg) diabetic rats either treated or not treated for 3 weeks with losartan, an AT-II type 1 receptor antagonist (20 mg/kg/day); we measured 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels, as an index of oxidative DNA damage, circulating Adp and FRAP. Diabetic rats showed significantly higher 8-oxodGuo levels in renal DNA (8.48 ± 0.98 × 10(-6) dG, mean ± SEM n = 11) than normoglycemic ones (1.18 ± 0.04 × 10(-6) dG, mean ± SEM, n=7) and lower plasma Adp and FRAP levels in comparison to normoglycemics. The treatment of diabetic rats with losartan significantly (P < 0.01) reduced 8-oxodGuo levels (5.4 ± 0.58 × 10(-6) dG, mean ± SEM n=9) in renal DNA and conserved FRAP values. Moreover, an inverse correlation was found between 8-oxodGuo in kidney DNA and circulating Adp levels in normoglycemic and diabetic rats. Losartan treatment preserves FRAP levels, reduces DNA oxidative injury and thus the carcinogenesis risk. Furthermore, our results indicate that Adp plasma levels are a further marker of oxidative injury to the kidney and confirm that it is an important part of the plasma antioxidant defense.

  9. Centella asiatica Attenuates Diabetes Induced Hippocampal Changes in Experimental Diabetic Rats

    PubMed Central

    Srinivasarao, Nelli; Swapna Rekha, Somesula; Muniandy, Sekaran

    2014-01-01

    Diabetes mellitus has been reported to affect functions of the hippocampus. We hypothesized that Centella asiatica, a herb traditionally being used to improve memory, prevents diabetes-related hippocampal dysfunction. Therefore, the aim of this study was to investigate the protective role of C. asiatica on the hippocampus in diabetes. Methods. Streptozotocin- (STZ-) induced adult male diabetic rats received 100 and 200 mg/kg/day body weight (b.w) C. asiatica leaf aqueous extract for four consecutive weeks. Following sacrifice, hippocampus was removed and hippocampal tissue homogenates were analyzed for Na+/K+-, Ca2+- and Mg2+-ATPases activity levels. Levels of the markers of inflammation (tumor necrosis factor, TNF-α; interleukin, IL-6; and interleukin, IL-1β) and oxidative stress (lipid peroxidation product: LPO, superoxide dismutase: SOD, catalase: CAT, and glutathione peroxidase: GPx) were determined. The hippocampal sections were visualized for histopathological changes. Results. Administration of C. asiatica leaf aqueous extract to diabetic rats maintained near normal ATPases activity levels and prevents the increase in the levels of inflammatory and oxidative stress markers in the hippocampus. Lesser signs of histopathological changes were observed in the hippocampus of C. asiatica leaf aqueous extract treated diabetic rats. Conclusions. C. asiatica leaf protects the hippocampus against diabetes-induced dysfunction which could help to preserve memory in this condition. PMID:25161691

  10. Anti-diabetic effect of Capparis spinosa L. root extract in diabetic rats

    PubMed Central

    Kazemian, Mostafa; Abad, Mansur; Haeri, Mohammad reza; Ebrahimi, Mansoor; Heidari, Reza

    2015-01-01

    Objective: Diabetes mellitus is the most common metabolic disorders with severe impact on quality of life. Reducing serum glucose levels and normalization of serum lipid is of great clinical importance for treating diabetes. To our knowledge, there are not any evidences about the anti-diabetic action of capparis spinosa root. In the present study the effects of the C. spinosa root extract on diabetic metabolic disorders have been studied in experimental diabetes. Materials and Methods: Rats were divided into six groups: normal control (NC), diabetic control (DC), diabetic rats receiving 0.2, 0.4 g/kg of plant extract or 0.6 mg/kg glibenclamide (groups D0.2, D0.4 or DG respectively). A normal group of rats was also designed to receive 0.2 g/kg of plant extract (N0.2). Rats were rendered diabetic (streptozotocin 60 mg/kg, i.p.) and treated with 0.2, 0.4 g/ kg of plant extract or glibenclamide for four weeks. At the end of the experiment, blood was drawn through heart puncture under deep anesthesia. Weight was measured weekly, glucose levels were measured at the first and fourth week and lipid profiles, insulin and liver enzymes at the end of the study. Results: Glucose levels significantly decreased after treating with plant extract (p=0.003). However, insulin levels did not increase in any treating groups. Plant extract could significantly raise HDL and reduce levels of LDL and liver enzymes (ALT and ALP). Conclusion: These results showed that C. spinosa root extract could improve diabetic related metabolic derangement such as hyperglycemia, dyslipidemia, and elevated liver markers in an insulin-independent manner. PMID:26445712

  11. Streptozotocin-Induced Diabetic Models in Mice and Rats.

    PubMed

    Furman, Brian L

    2015-09-01

    Streptozotocin (STZ) is an antibiotic that produces pancreatic islet β-cell destruction and is widely used experimentally to produce a model of type 1 diabetes mellitus (T1DM). Detailed in this unit are protocols for producing STZ-induced insulin deficiency and hyperglycemia in mice and rats. Also described are protocols for creating animal models for type 2 diabetes using STZ. These animals are employed for assessing the pathological consequences of diabetes and for screening potential therapies for the treatment of this condition.

  12. Adiponectin trajectories before type 2 diabetes diagnosis: Whitehall II study.

    PubMed

    Tabák, Adam G; Carstensen, Maren; Witte, Daniel R; Brunner, Eric J; Shipley, Martin J; Jokela, Markus; Roden, Michael; Kivimäki, Mika; Herder, Christian

    2012-12-01

    The role of adiponectin in the natural history of diabetes is not well characterized. We set out to characterize prediagnosis trajectories of adiponectin in individuals who develop type 2 diabetes. In a case-cohort study (335 incident diabetes case and 2,474 noncase subjects) nested in the Whitehall II study, serum adiponectin was measured up to three times per participant (1991-1993, 1997-1999, and 2003-2004). Multilevel models adjusted for age and ethnicity were fitted to assess 13-year trajectories of log-transformed adiponectin preceding diabetes diagnosis or a randomly selected time point during follow-up (year(0)) based on 755/5,095 (case/noncase) person-examinations. Adiponectin levels were lower in diabetes case than in noncase subjects (median 7,141 [interquartile range 5,187-10,304] vs. 8,818 [6,535-12,369] ng/mL at baseline, P < 0.0001). Control subjects showed a modest decline in adiponectin throughout follow-up (0.3% per year, P < 0.0001) at higher levels in women than in men (difference at year(0): 5,358 ng/mL, P < 0.0001). Female case and early-onset case (age at diagnosis <52 years) subjects had a steeper decline than control subjects (slope difference -1.1% per year, P = 0.001 in females, -1.6% per year in early-onset case subjects, P = 0.034). In men, adiponectin slopes for case and noncase subjects were parallel. The slope differences by diabetes onset were largely attenuated after adjustment for changes in obesity, whereas the sex-specific slope differences were independent of obesity. Lower adiponectin levels were observed already a decade before the diagnosis of diabetes. The marked sex difference in trajectories suggests that sex-specific mechanisms affect the association between adiponectin levels and diabetes development.

  13. Effects of enalapril, losartan, and verapamil on blood pressure and glucose metabolism in the Cohen-Rosenthal diabetic hypertensive rat.

    PubMed

    Rosenthal, T; Erlich, Y; Rosenmann, E; Cohen, A

    1997-06-01

    We undertook the present study to examine the effect of the angiotensin-converting enzyme inhibitor enalapril, the angiotensin II antagonist losartan, and calcium antagonist verapamil on systolic pressure and spontaneous blood glucose levels in rats from the Cohen-Rosenthal diabetic hypertensive strain. Genetic hypertension and diabetes developed in this strain after crossbreeding of Cohen diabetic and spontaneously hypertensive rats. The new rat strain was fed their usual copper-poor sucrose diet, which is essential for the development of this model, and for 4 weeks received either enalapril, losartan, or verapamil. Systolic pressure was reduced significantly compared with controls in all treated groups. Chronic treatment with enalapril or verapamil, but not with losartan, succeeded in lowering spontaneous blood glucose, indicating improved diabetic control. Data suggest that angiotensin-converting enzyme inhibition by enalapril, but not angiotensin II antagonism by losartan, can improve glucose metabolism in addition to its hypotensive effect in a genetic diabetic hypertensive rat strain. This confirms that the drop in glucose with converting enzyme inhibition is highly dependent on bradykinin accumulation. Data further suggest that calcium channel blockade by verapamil can also improve glucose metabolism. The question remains whether the reduction in glucose by verapamil was a result of inhibition of glucogenesis.

  14. Sex-specific programming of hypertension in offspring of late-gestation diabetic rats.

    PubMed

    Katkhuda, Ragheed; Peterson, Emily S; Roghair, Robert D; Norris, Andrew W; Scholz, Thomas D; Segar, Jeffrey L

    2012-10-01

    The intrauterine environment strongly influences adult disease susceptibility. We used a rat model of third-trimester maternal diabetes to test the hypothesis that adult offspring exposed to hyperglycemia in utero display increased blood pressure and alterations in vascular responsiveness. Diabetes was induced by streptozotocin injection to pregnant rats on gestation day 13 (term 21 d) and partially controlled with insulin injections. Hemodynamic function was evaluated in 6-12-mo-old offspring. Male but not female offspring of diabetic mothers (ODM) had significantly increased blood pressure as compared with controls; heart rate (HR) was similar. For both sexes, HR baroreflex responses were similar as were in vivo hemodynamic responses to angiotensin II, nitric oxide synthase inhibition, and ganglionic blockade. Aortic contractility to angiotensin II was similar in the two groups. Nitric oxide synthase inhibition and the Cu/Zn superoxide dismutase inhibitor diethyldithiocarbamate, but not the superoxide dismutase-mimetic Tempol, significantly increased contractile responses to angiotensin II in controls but not ODM. Reduced nicotinamide adenine dinucleotide phosphate-stimulated superoxide production was greater in male ODM than in controls (P < 0.05). Exposure to hyperglycemia in utero results in sex-specific cardiovascular changes in adult offspring. Impaired nitric oxide-reactive oxygen species signaling may play a significant role in the hemodynamic phenotype of ODM.

  15. Sex-Specific Programming of Hypertension in Offspring of Late Gestation Diabetic Rats

    PubMed Central

    Katkhuda, Ragheed; Peterson, Emily S.; Roghair, Robert D.; Norris, Andrew W.; Scholz, Thomas D.; Segar, Jeffrey L.

    2013-01-01

    Background The intrauterine environment strongly influences adult disease susceptibility. We utilized a rat model of third trimester maternal diabetes to test the hypothesis that adult offspring exposed to hyperglycemia in utero display increased blood pressure and alterations in vascular responsiveness. Methods Diabetes was induced by streptozotocin injection to pregnant rats on gestation day 13 (term 21 day) and partially controlled with insulin injections. Hemodynamic function was evaluated in 6–12 month old offspring. Results Male but not female offspring of diabetic mothers (ODM) had significantly increased blood pressure compared to controls, heart rate was similar. For both sexes, heart rate baroreflex responses were similar as were in vivo hemodynamic responses to angiotensin II, NOS inhibition and ganglionic blockade. Aortic contractility to angiotensin II was similar in both groups. NOS inhibition and the Cu/Zn superoxide dismutase (SOD) inhibitor diethyldithiocarbamate but not the SOD-mimetic Tempol significantly increased contractile responses to angiotensin II in controls but not ODM. NADPH stimulated superoxide production was greater in male ODM than controls (p<0.05). Conclusions Exposure to hyperglycemia in utero results in sex specific cardiovascular changes in adult offspring. Impaired NO - reactive oxygen species signaling may play a significant role in the hemodynamic phenotype of ODM. PMID:22805998

  16. Diabetes mellitus effect on rat corneal dielectric properties.

    PubMed

    Olszewski, J; Marzec, E; Florek, E; Kulza, M

    2012-03-01

    In the course of the study, we carried out a dielectric examination to determine the effect of diabetes mellitus on the rat corneal function. Measurements were performed over the frequency range of 500 Hz-100 kHz in air and at the temperatures from 25 to 150°C. The frequency dependencies of the loss tangent for the healthy and the diabetic cornea exhibit two peaks at 2 kHz and 16 kHz in the α-dispersion region. The amplitude of these both peaks is smaller for the diabetic cornea than that for the healthy one. The temperature dependencies of the loss tangent for the healthy and the diabetic cornea reveal β-relaxation in the range of 30-70°C and 50-90°C, respectively. The present study exhibits that the dielectric spectroscopy is useful in detection of the effect of diabetes mellitus on the corneal molecular behavior.

  17. Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells from a Diabetic Rat Model

    PubMed Central

    Keller, Amy C.; Knaub, Leslie A.; McClatchey, P. Mason; Connon, Chelsea A.; Bouchard, Ron; Miller, Matthew W.; Geary, Kate E.; Walker, Lori A.; Klemm, Dwight J.; Reusch, Jane E. B.

    2016-01-01

    Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs) from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK) and the Wistar control rat were exposed to high glucose (25 mM). At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR) were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (p < 0.05). Mitochondrial superoxide increased with high glucose in Wistar SMCs (p < 0.05) with no change in the GK beyond elevated baseline concentrations. Baseline comparisons show persistent metabolic perturbations in a diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets. PMID:27034743

  18. Diabetic cardiomyopathy: effects of fenofibrate and metformin in an experimental model – the Zucker diabetic rat

    PubMed Central

    Forcheron, Fabien; Basset, Alexandra; Abdallah, Pauline; Del Carmine, Peggy; Gadot, Nicolas; Beylot, Michel

    2009-01-01

    Background Diabetic cardiomyopathy (DCM) contributes to cardiac failure in diabetic patients. It is characterized by excessive lipids accumulation, with increased triacylglycerol (TAG) stores, and fibrosis in left ventricle (LV). The mechanisms responsible are incompletely known and no specific treatment is presently defined. We evaluated the possible usefulness of two molecules promoting lipid oxidation, fenofibrate and metformin, in an experimental model of DCM, the Zucker diabetic rat (ZDF). Methods ZDF and controls (C) rats were studied at 7, 14 and 21 weeks. After an initial study at 7 weeks, ZDF rats received no treatment, metformin or fenofibrate until final studies (at 14 or 21 weeks). C rats received no treatment. Each study comprised measurements of metabolic parameters (plasma glucose, TAG, insulin levels) and sampling of heart for histology and measurements of TAG content and relevant mRNA concentration. Results ZDF rats were insulin-resistant at 7 weeks, type 2 diabetic at 14 weeks and diabetic with insulin deficiency at 21 weeks. Their plasma TAG levels were increased. ZDF rats had at 7 weeks an increased LV TAG content with some fibrosis. LV TAG content increased in untreated ZDF rats at 14 and 21 weeks and was always higher than in C. Fibrosis increased also moderately in untreated ZDF rats. Metformin and fenofibrate decreased plasma TAG concentrations. LV TAG content was decreased by metformin (14 and 21 weeks) and by fenofibrate (14 weeks). Fibrosis was reduced by fenofibrate only and was increased by metformin. Among the mRNA measured, fenofibrate increased Acyl-CoA Oxidase mRNA level, metformin decreased Acyl-CoA Synthase and increased AdipoR1 and pro-inflammatory mRNA levels. Conclusion Fenofibrate had favourable actions on DCM. Metformin had beneficial effect on TAG content but not on fibrosis. PPARα agonists could be useful for the prevention and treatment of DCM. PMID:19317897

  19. Effects of Momordica charantia on pancreatic histopathological changes associated with streptozotocin-induced diabetes in neonatal rats.

    PubMed

    Abdollahi, M; Zuki, A B Z; Goh, Y M; Rezaeizadeh, A; Noordin, M M

    2011-01-01

    The aim of this research was to determine the effects of Momordica charantia (MC) fruit aqueous extract on pancreatic histopathological changes in neonatal STZ-induced type-II diabetic rats. Diabetes mellitus was induced in one day Sprague-Dawley neonatal rats using a single intrapretoneal injection of streptozotocin (STZ) (85 mg/kg body weight) and monitored for 12 weeks thereafter. The diabetic rats were separated into three groups, as follows: the diabetic control group (i.e. nSTZ), the diabetic group (i.e. nSTZ/M) - which was orally given 20 mg/kg of MC fruit extract, and the diabetic group (i.e. nSTZ/G) - that was treated with glibenclamide, 0.1 mg/kg for a period of four weeks. At the end of treatment, the animals were sacrificed and blood samples were collected from the saphenous vein to measure the blood glucose and serum insulin level. The pancreatic specimens were removed and processed for light microscopy, electron microscopy examination and immunohistochemical study. The results of this study showed that MC fruit aqueous extract reduced the blood glucose level as well as glibenclamide and increased the serum insulin level in the treated diabetic rats (P<0.05). The fruit extract of MC alleviated pancreatic damage and increased the number of β-cells in the diabetic treated rats (P<0.05). Our results suggest that oral feeding of MC fruit extract may have a significant role in the renewal of pancreatic β-cells in the nSTZ rats.

  20. Lipidemic effects of common edible oils and risk of atherosclerosis in diabetic Wistar rats

    PubMed Central

    Oladapo, Olulola Olutoyin; Ojora, Kehinde Adeyemi; Quadri, Oluwafemi Majeed; Ajani, Rotimi Sunday

    2017-01-01

    BACKGROUND Diabetic state potentiates atherosclerosis and the type of edible oil consumed by the individual may affect this further. This study aimed to determine if the common edible oils in Nigeria have any effects on the lipid profiles and arteries of alloxan-induced diabetic male Wistar rats. METHODS Thirty male Wistar rats were randomly divided into five groups of normal control, diabetic control, animals on diet enriched with refined, bleached deodorized palm oil (RBD-PO), animals on diet enriched with soya oil, and animals on diet enriched with olive oil. At the end of 8 weeks, the lipid profiles of the animals were determined before sacrificing them. Their aortas were subsequently harvested for histological examination. RESULTS The olive oil fed group had the highest level of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), lowest HDL-C, and highest artherogenic index (AI). Diabetic animals fed on RBD-PO had a lower non-HDL-C, higher HDL-C, and lower AI than diabetic animals fed on olive oil or soya oil. However, the diabetic animals fed on RBD-PO had the highest triglyceride level. When the aortas were examined histologically, there were no atherosclerotic lesions in all the control and experimental groups except those fed on 10% soya oil enriched diet that had type II atherosclerotic lesions according to American Heart Association (AHA). CONCLUSION The result of our study showed that RBD-PO appears to offer a better lipid profile in the diabetic animals compared with olive oil and soya oil. Soya oil appears to cause the development of atherosclerosis in diabetic state. PMID:28761450

  1. Lipidemic effects of common edible oils and risk of atherosclerosis in diabetic Wistar rats.

    PubMed

    Oladapo, Olulola Olutoyin; Ojora, Kehinde Adeyemi; Quadri, Oluwafemi Majeed; Ajani, Rotimi Sunday

    2017-01-01

    Diabetic state potentiates atherosclerosis and the type of edible oil consumed by the individual may affect this further. This study aimed to determine if the common edible oils in Nigeria have any effects on the lipid profiles and arteries of alloxan-induced diabetic male Wistar rats. Thirty male Wistar rats were randomly divided into five groups of normal control, diabetic control, animals on diet enriched with refined, bleached deodorized palm oil (RBD-PO), animals on diet enriched with soya oil, and animals on diet enriched with olive oil. At the end of 8 weeks, the lipid profiles of the animals were determined before sacrificing them. Their aortas were subsequently harvested for histological examination. The olive oil fed group had the highest level of total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), lowest HDL-C, and highest artherogenic index (AI). Diabetic animals fed on RBD-PO had a lower non-HDL-C, higher HDL-C, and lower AI than diabetic animals fed on olive oil or soya oil. However, the diabetic animals fed on RBD-PO had the highest triglyceride level. When the aortas were examined histologically, there were no atherosclerotic lesions in all the control and experimental groups except those fed on 10% soya oil enriched diet that had type II atherosclerotic lesions according to American Heart Association (AHA). The result of our study showed that RBD-PO appears to offer a better lipid profile in the diabetic animals compared with olive oil and soya oil. Soya oil appears to cause the development of atherosclerosis in diabetic state.

  2. Antinociceptive Effect of Mirtazapine in Rats with Diabetic Neuropathy

    PubMed Central

    İNAL, Ahmet; BÜYÜKŞEKERCİ, Murat; ULUSOY, Hasan Basri

    2016-01-01

    Introduction To evaluate the antinociceptive effect of mirtazapine and the mechanisms mediating this effect in neuropathic pain in rats with diabetes. Methods The experiments were performed in Sprague Dawley rats using a hot-plate device. Streptozotocin (STZ) was administered to the rats after taking control measurements. Rats with a blood glucose level of 240 mg/dL or above in the blood specimen obtained from the tail vein 3 days after STZ administration were considered as being diabetic. Three weeks after STZ administration, the hot-plate test was performed. Compared with the control measurements, rats that exhibited >20% decrease in the second hot-plate test measurements were considered to have developed neuropathy. Drugs [mirtazapine, naloxone (opioidergic antagonist), metergoline (serotonergic antagonist), and BRL44408 (adrenergic antagonist)] and drug combinations were administered to those rats that developed neuropathy. After administrating the drugs or drug combinations, the third hot-plate test was performed. Results Mirtazapine at doses of 10 and 15 mg/kg exhibited a significant antinociceptive effect. Naloxone, metergoline, or BRL44408 alone did not cause an antinociceptive effect. However, combinations of these drugs with mirtazapine (15 mg/kg) significantly decreased the antinociceptive effect of mirtazapine. Conclusion It is suggested that mirtazapine has a significant antinociceptive effect in diabetic neuropathy and that opioidergic, serotonergic, and adrenergic systems have roles to play in this effect. PMID:28360759

  3. Type II Diabetes Mellitus in Arabic-Speaking Countries

    PubMed Central

    Badran, Mohammad; Laher, Ismail

    2012-01-01

    The global epidemic of diabetes has not spared the Arabic-speaking countries, which have some of the highest prevalence of type II diabetes. This is particularly true of the Arab Gulf, a conglomerate of high income, oil-producing countries where prevalence rates are the highest. The prevalence rates among adults of the Arabic speaking countries as a whole range between 4%–21%, with the lowest being in Somalia and the highest in Kuwait. As economic growth has accelerated, so has the movement of the populations to urban centers where people are more likely to adopt lifestyles that embrace increased high-calorie food consumption and sedentary lifestyles. These factors likely contribute to the increased prevalence of obesity and diabetes in the Arabic speaking countries. PMID:22851968

  4. Renal fibrosis in diabetic and aortic-constricted hypertensive rats.

    PubMed

    Gallego, B; Arévalo, M A; Flores, O; López-Novoa, J M; Pérez-Barriocanal, F

    2001-06-01

    To assess if the renal damage observed in rats with diabetes and hypertension is due to hemodynamic or metabolic changes, a progressive aortic constriction between the two renal arteries has been done in streptozotocin-induced diabetic rats (constriction + diabetes group) and in nondiabetic rats (constriction group). This model allows us to study two kidneys subjected to different perfusion pressure (PP) in the same metabolic environment. One-month-old rats (100-120 g body wt) were subjected to the aortic constriction procedure. Three months after constriction, glomerular filtration rate and renal plasma flow were similar in both kidneys of the two groups. PP was greater in the kidney placed over the ligature [constriction high-pressure kidney (CH) or constriction + diabetic high-pressure kidney (DH)] than in the one placed below the ligature [constriction low pressure (CL) or constriction + diabetic low pressure (DL)]. Proteinuria was higher in the CH than in the CL kidneys (512 +/- 61 vs. 361 +/- 38 microg/30 min, respectively) and much higher in the DH kidney (770 +/- 106 microg/30 min). Renal fibrosis was measured in tissue sections stained with Syrius red using a computer-assisted image analysis system. DH and DL kidneys showed higher corpuscular cross-sectional and capillary tuft areas than the CH and CL ones. The DH kidney showed slight mesangial expansion and thickening of the capillary walls, which were more pronounced in the former. Most renal corpuscles from CH and DH groups were nearly normal in morphology appearance, and only in some instances a slight increment in mesangium was observed. Transforming growth factor-beta1 (TGF-beta1) immunostaining revealed that DH kidneys showed the highest glomerular expression. We concluded that 1) diabetic animals develop glomerular but not interstitial fibrosis to a greater extent than nondiabetic animals and that this lesion principally occurs in the hypertensive kidney (DH), and 2) increased TGF-beta expression

  5. The variation of macro- and micro-minerals of tissues in diabetic and non-diabetic rats.

    PubMed

    Presley, Tennille D; Duncan, A'ja V; Jeffers, Anne B; Fakayode, Sayo O

    2017-01-01

    This study determined the levels of Ca, Mg, Fe, Zn, Cu, and Na in various tissues samples (liver, brain, kidney, intestines, muscle and hair) of diabetic and non-diabetic rats by flame atomic absorption spectroscopy, in order to assess the role of element levels during T2DM. The ratios of Ca/Mg, Zn/Cu, Ca/Zn, and Mg/Zn in diabetic and non-diabetic rat tissues were also calculated. The determined element levels were further subjected to a student-t test statistical analysis and multiple-linear-regression in order to evaluate similarities, differences, and an inter-element association in tissues of diabetic and non-diabetic rats. The results of the study showed high variability in element levels and Ca/Mg Zn/Cu Mg/Zn Ca/Zn ratios in the tissues of diabetic and non-diabetic rats, but are tissue- and element-dependent, suggesting differences in the accumulation of the elements in tissues of diabetics and non-diabetics. The obtained significant differences in the levels of elements and Ca/Mg Zn/Cu Mg/Zn Ca/Zn ratios in several tissues of diabetic and non-diabetic rats in this study suggest that the investigated elements play considerable roles in the T2DM disease process. Strong inter-element associations (R(2)≥0.9) were observed for some elements in tissues of diabetic and non-diabetics rats. However, poor inter-elemental associations were obtained for some elements in the tissues of diabetic and non-diabetic rats. Published by Elsevier GmbH.

  6. Ibuprofen attenuates nephropathy in streptozotocin‑induced diabetic rats.

    PubMed

    Liu, Yao-Wu; Zhu, Xia; Cheng, Ya-Qin; Lu, Qian; Zhang, Fan; Guo, Hao; Yin, Xiao-Xing

    2016-06-01

    Ibuprofen, a commonly administered nonsteroidal anti‑inflammatory therapeutic agent, is also a partial agonist of peroxisome proliferator‑activated receptor γ (PPARγ). The present study investigated the effects of ibuprofen on type 1 diabetic nephropathy (DN) in rats, and the potential mechanisms associated with the activation of PPARγ. Diabetic rats were induced through a single intraperitoneal injection of streptozotocin before oral treatment with ibuprofen or pioglitazone for 8 weeks. The 24‑h urine collection was performed for measurement of total protein content. The kidney was fixed in 10% formalin for periodic acid‑Schiff and Masson's trichrome staining. Blood and residual kidney tissue samples were collected to measure the associated biochemical parameters. Chronic ibuprofen treatment decreased urinary protein excretion, blood urea nitrogen, glomerular basement membrane thickening and renal fibrosis, which were accompanied by increases in PPARγ protein expression, glutathione (GSH) level, and superoxide dismutase (SOD) activity, decreases in cyclooxygenase 2 and inducible nitric oxide synthase protein expressions, as well as a decreased interleukin 1β (IL‑1β) level in the renal cortex of DN rats. Furthermore, the reduced IL‑1β level, increased GSH quantities and stronger SOD activity in the rat serum were evaluated in ibuprofen‑treated diabetic rats and were compared with untreated diabetic rats. Regarding GSH and IL‑1β levels, ibuprofen was identified to be superior to the positive control, pioglitazone, while levels of the other indices were identified to be similar. Thus, ibuprofen was observed to prevent the development of DN, caused by type 1 diabetes, by anti‑inflammatory and anti‑oxidative action, potentially via PPARγ activation.

  7. [Ameliorative effects on retinal disorder in diabetic SHRSP (stroke-prone spontaneously hypertensive rat)].

    PubMed

    Nagisa, Yasutaka; Shintani, Asae; Nakagawa, Shizue

    2002-10-01

    The results of the EUCLID highlighted the importance of the renin-angiotensin system in the pathogenesis of diabetic retinopathy. We aimed to evaluate the effectiveness of candesartan cilexetil(TCV-116), a potent angiotensin II receptor antagonist, in ameliorating retinal disorders in stroke-prone spontaneously hypertensive rats(SHRSP) with storeptozotocin(STZ)-induced diabetes. Retinal VEGF mRNA expression was significantly higher and the latencies of oscillatory potentials were significantly elongated in STZ-treated SHRSP compared with a non-treated SHRSP group matched for age. Treatment with TCV-116(3 mg/kg) significantly diminished retinal VEGF mRNA expression and the latencies of oscillatory potentials, but had no effect on plasma glucose concentrations. These results suggest that TCV-116 is effective in preventing the development of diabetic retinopathy already in the early stages.

  8. Saengshik, a formulated health food, decreases blood glucose and increases survival rate in streptozotocin-induced diabetic rats.

    PubMed

    Kim, Meesook; Kim, Eul-Sang; Park, Mi-Hyoun; Hwang, Sung-Joo; Jeong, Yoonhwa

    2004-01-01

    Saengshik is a Korean "non-cooked food" that is commercially produced and marketed. Ingredients in commercial Saengshik include grains, vegetables, fruits, mushrooms, sea plants, and various functional botanicals. This study investigated the effects of Saengshik on the survival rate of streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats weighing around 190 g were randomly assigned to one of the three experimental groups: a healthy normal group (NC) and two groups with STZ-induced diabetes and fed either control diet (DC) or Saengshik diet (DS). Rats in all groups were supplied with a diet of equal energy. The animals were maintained on an experimental diet for 168 days in experiment I and for 42 days in experiment II. The body weight in the DS rats decreased less than in the DC rats in both experiments I and II. There was a trend for blood glucose level in the DS group to decrease during the experimental period in both experiments I and II. A survival rate of 50% was reached on day 49 in the DC group and on day 118 in the DS group. All rats in the DC group died by day 140, while 50% of the rats in the DS group were still alive on day 168, when experiment I was terminated. In experiment II, 50% of the DC group and 90% of the DS group survived at day 42. Saengshik did not have any influence on cholesterol levels, thiobarbituric acid-reactive substances, and activities of superoxide dismutase and glutathione peroxidase. These results suggest that blood glucose concentrations and the survival rate are positively affected by Saengshik feeding in diabetic rats.

  9. Studies on the antidiabetic activities of Momordica charantia fruit juice in streptozotocin-induced diabetic rats.

    PubMed

    Mahmoud, Mona F; El Ashry, Fatma El Zahraa Z; El Maraghy, Nabila N; Fahmy, Ahmed

    2017-12-01

    Momordica charantia Linn (Cucurbitaceae) (MC) is used in folk medicine to treat various diseases including diabetes mellitus. This study investigates the antidiabetic activities of Momordica charantia (bitter gourd) on streptozotocin-induced type 2 diabetes mellitus in rats. Male Wister rats were randomly assigned to 4 groups. Group I, Normal control; Group II, STZ diabetic; Group III and IV, Momordica charantia fruit juice was orally administered to diabetic rats (10 mL/kg/day either as prophylaxis for 14 days before induction of diabetes then 21 days treatment, or as treatment given for 21 days after induction of diabetes). The effects of MC juice were studied both in vivo and in vitro by studying the glucose uptake of isolated rat diaphragm muscles in the presence and absence of insulin. Histopathological examination of pancreas was also performed. This study showed that MC caused a significant reduction of serum glucose (135.99 ± 6.27 and 149.79 ± 1.90 vs. 253.40* ± 8.18) for prophylaxis and treatment respectively, fructosamine (0.99 ± 0.01 and 1.01 ± 0.04 vs. 3.04 ± 0.07), total cholesterol, triglycerides levels, insulin resistance index (1.13 ± 0.08 and 1.19 ± 0.05 vs. 1.48 ± 1.47) and pancreatic malondialdehyde content (p < 0.05). While it induced a significant increase of serum insulin (3.41 ± 0.08 and 3.28 ± 0.08 vs. 2.39 ± 0.27), HDL-cholesterol, total antioxidant capacity levels, β cell function percent, and pancreatic reduced glutathione (GSH) content (p < 0.05) and improved histopathological changes of the pancreas. It also increased glucose uptake by diaphragms of normal (12.17 ± 0.60 vs. 9.07 ± 0.66) and diabetic rats (8.37 ± 0.28 vs. 4.29 ± 0.51) in the absence and presence of insulin (p < 0.05). Momordica charantia presents excellent antidiabetic and antioxidant activities and thus has great potential as a new source for diabetes treatment whether it is

  10. [Diabetes insipidus in infancy. II. Study of eleven cases (author's transl)].

    PubMed

    de Yturriaga, R; Barrio, R; Nieto, J A; Rabadán, B; Lledó, G; Gracia, R

    1977-01-01

    Eleven cases of diabetes insipidus are revised and distributed in the following four groups: I. Idiopathic diabetes insipidus, three. II. Secondary diabetes insipidus, four. III. Nephrogenic diabetes insipidus, two. IV. Psychogenic diabetes insipidus, two. In all these cases, clinical parameters, general analysis, hydric metabolism (static and dinamic), are studied. The precocious beginning of psychogenic diabetes insipidus, and some conclusions, on a difficult case of hard diagnosis are emphasized.

  11. Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Kant, Vinay; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surendra K; Kumar, Dinesh

    2014-06-01

    Prolonged inflammation and increased oxidative stress impairs healing in diabetics and application of curcumin, a well known antioxidant and anti-inflammatory agent, could be an important strategy in improving impaired healing in diabetics. So, the present study was conducted to evaluate the cutaneous wound healing potential of topically applied curcumin in diabetic rats. Open excision skin wound was created in streptozotocin induced diabetic rats and wounded rats were divided into three groups; i) control, ii) gel-treated and iii) curcumin-treated. Pluronic F-127 gel (25%) and curcumin (0.3%) in pluronic gel were topically applied in the gel- and curcumin-treated groups, respectively, once daily for 19 days. Curcumin application increased the wound contraction and decreased the expressions of inflammatory cytokines/enzymes i.e. tumor necrosis factor-alpha, interleukin (IL)-1beta and matrix metalloproteinase-9. Curcumin also increased the levels of anti-inflammatory cytokine i.e. IL-10 and antioxidant enzymes i.e. superoxide dismutase, catalase and glutathione peroxidase. Histopathologically, the curcumin-treated wounds showed better granulation tissue dominated by marked fibroblast proliferation and collagen deposition, and wounds were covered by thick regenerated epithelial layer. These findings reveal that the anti-inflammatory and antioxidant potential of curcumin caused faster and better wound healing in diabetic rats and curcumin could be an additional novel therapeutic agent in the management of impaired wound healing in diabetics.

  12. The protective effects of DA-9801 (Dioscorea extract) on the peripheral nerves in streptozotocin-induced diabetic rats.

    PubMed

    Lee, Kyung Ae; Jin, Heung Yong; Baek, Hong Sun; Park, Tae Sun

    2013-01-01

    It has been reported that DA-9801, an extract mixture of Dioscorea japonica Thunb and Dioscorea nipponica Makino, produces a neurotrophic activity. Therefore, this study was conducted to examine the neuroprotective effects of DA-9801 in streptozotocin-induced diabetic rats. The experimental rats were divided into six groups: the control group, Group I (non-diabetic rats treated with DA-9801), Group II (diabetic, non-treated rats) and Groups III, IV, and V (diabetic rats treated with DA-9801 at doses of 10, 50 or 100 mg/kg/d). Following a 16-wk course of oral treatment with DA-9801, functional parameters (von Frey filament test, hot plate test), biochemical parameters (nerve growth factor (NGF), tumor necrosis factor (TNF)-α, interleukin (IL)-6) were measured. An immunohistochemical staining was done to assess the neuroprotective effects of DA-9081 in the skin, sciatic nerve, gastric mucosa and renal cortex. In Week 8, pain was evoked by either tactile or thermal stimuli, whose threshold was significantly higher in Group III, IV and V than Group II. Western blot analysis showed a more significant increase in NGF and decrease in TNF-α and IL-6 in Group III, IV and V than in Group II (p<0.05). Moreover, following the treatment with DA-9801, a loss of intraepidermal nerve fibers (IENFs) was inhibited to a significant level in the skin, myelinated axonal fibers of the sciatic nerve and small nerve fibers innervating the gastric mucosa or renal cortex (p<0.05). Our results demonstrated that DA-9801 is a beneficial agent that protects the peripheral nerves in diabetic rats.

  13. The angiotensin II receptor antagonist candesartan cilexetil (TCV-116) ameliorates retinal disorders in rats.

    PubMed

    Nagisa, Y; Shintani, A; Nakagawa, S

    2001-07-01

    The results of the EUCLID trial (EURODIAB Controlled Trial of Lisinopril in Insulin-dependent Diabetes Mellitus) highlighted the importance of the renin-angiotensin system in the pathogenesis of diabetic retinopathy. Candesartan cilexetil (TCV-116), a potent angiotensin II (AII) receptor antagonist, has beneficial effects on hypertension as well as on heart, renal and cerebrovascular disease. We aimed to evaluate the effectiveness of candesarten cilexetil in ameliorating retinal disorders induced by hyperglycaemia. We compared retinal vascular endothelial growth factor (VEGF) mRNA expression and the latencies of retinal oscillatory potentials in TCV-116-treated and control groups of stroke-prone spontaneously hypertensive rats with streptozocin (STZ)-induced diabetes. Retinal VEGF mRNA expression was significantly higher and the latencies of oscillatory potentials were significantly elongated in STZ-treated spontaneously hypertensive rats compared with a non-treated spontaneously hypertensive rat group matched for age. These changes were dependent on hyperglycaemia but independent of hypertension. Treatment with TCV-116 (3 mg/kg) significantly diminished retinal VEGF mRNA expression and the latencies of oscillatory potential peaks, but had no effect on plasma glucose concentrations. These results suggest that TCV-116 is effective in preventing the development of diabetic retinopathy already in the early stages.

  14. Antioxidant potential of bilirubin-accelerated wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Ram, Mahendra; Singh, Vishakha; Kumar, Dhirendra; Kumawat, Sanjay; Gopalakrishnan, Anu; Lingaraju, Madhu C; Gupta, Priyanka; Tandan, Surendra Kumar; Kumar, Dinesh

    2014-10-01

    Oxidative injury is markedly responsible for wound complications in diabetes mellitus. The biological actions of bilirubin may be relevant to prevent oxidant-mediated cell death, as bilirubin application at a low concentration scavenges reactive oxygen species. Hence, we hypothesized that topical bilirubin application might improve wound healing in diabetic rats. Diabetes was induced in adult male Wistar rats, which were divided into two groups, i.e., diabetic control and diabetic treated. Non-diabetic healthy rats were also taken as healthy control group. Wound area was measured on days 3, 7, 14, and 19 post-wounding. The levels of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in the granulation tissue. There was a significant increase in percent wound closure in healthy control and diabetic treated rats on days 7, 14, and 19, as compared to diabetic control rats on days 7, 14, and 19. There was significant decrease in MDA levels on days 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. Levels of GSH were significantly increased on days 3, 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. GPx, SOD, and CAT activities were significantly higher on days 3, 7, and 14 in diabetic treated rats, as compared to diabetic control rats. The findings indicate that bilirubin is effective in reducing the oxidant status in wounds of diabetic rats which might have accelerated wound healing in these rats.

  15. Tolerance to beta,beta'-iminodipropionitrile (IDPN)-induced neurobehavioural and vestibular toxicity in diabetic rats.

    PubMed

    Tariq, M; Khan, H A; Moutaery, K A; Deeb, S A

    1999-01-01

    The present investigation was undertaken to study the neurotoxic effects of beta,beta'-iminodipropionitrile (IDPN) in normal, diabetic and insulin-treated diabetic rats. Sprague-Dawley male rats were divided into five groups: control, IDPN, diabetes, diabetes plus IDPN and diabetes plus insulin plus IDPN. The diabetes was induced with a single i.p. injection of streptozotocin (50 mg kg(-1)). One month after the induction of diabetes, the rats were treated with IDPN (100 mg kg(-1), i.p.) daily for 11 days. One of the diabetic groups treated with IDPN also received daily injection of insulin (25 U kg(-1), s.c.), 1 h before IDPN. The rats were observed daily for abnormal head movements and circling. The grip strength of the forelimbs was also measured. In the IDPN group the dyskinetic symptoms appeared on the 8th day, whereas the onset of dyskinesia was on the 12th day in IDPN-treated diabetic rats. The incidence and severity of dyskinesia were significantly higher in IDPN-treated normal (non-diabetic) rats as compared to IDPN-treated diabetic rats. The treatment of diabetic rats with insulin normalized striatal dopamine (DA) turnover but partially reversed diabetes-induced protection against IDPN dyskinesia. There was severe degeneration of sensory hair cells in crista ampullaris of IDPN-treated normal rats, whereas the diabetic rats showed significant protection against IDPN-induced vestibular hair cell degeneration. In conclusion, our study clearly demonstrates that diabetic rats are resistant to IDPN-induced neurobehavioural and vestibular toxicity. The results also show that diabetes-induced protection against IDPN-induced dyskinesia can be partially reversed by insulin. The mechanism behind the decreased vulnerability of diabetic animals to IDPN remains to be resolved. Further studies are warranted to investigate this paradoxical phenomenon.

  16. Combating Combination of Hypertension and Diabetes in Different Rat Models

    PubMed Central

    Rosenthal, Talma; Younis, Firas; Alter, Ariela

    2010-01-01

    Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD), and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH) rats. The use of various drugs, such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs), various angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs), to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment. PMID:27713282

  17. Mallotus roxburghianus modulates antioxidant responses in pancreas of diabetic rats.

    PubMed

    Roy, V K; Chenkual, L; Gurusubramanian, G

    2016-03-01

    Mallotus roxburghianus has long been used by Mizo tribal people for the treatment of diabetes. Scientific validation at known doses may provide information about its safety and efficacy. Methanolic leaf extract of M. roxburghianus (MRME 100 and 400mg/kg) was tested in comparison with normal and alloxan diabetic rats for 28 days p.o. in terms of body and pancreatic weight, blood glucose level, antioxidant enzymes, expression of visfatin and PCNA, histopathology and histomorphometric measurements of pancreas. The results were evaluated statistically using ANOVA, correlation and regression and Principal component analysis (PCO). MRME (100 and 400mg/kg) treatment significantly (p<0.0001) decreased the body weight, blood glucose level, improved the mass and size of pancreas, elevated the levels of antioxidant enzymes and up regulate the expression of visfatin and PCNA. PCO analysis was good to fitness and prediction distinguishes the therapeutic effects of M. roxburghianus from the alloxan induced diabetic rats. MRME has significant role in protecting animals from alloxan-induced diabetic oxidative stress in pancreas and exhibited promising antihyperglycaemic and antioxidant activities along with significant reversal of disturbed antioxidant status and lipid peroxidative damage. Pancreatic architecture and physiology under diabetic oxidative stress have been significantly modulated by MRME and validated as a drug candidate for antidiabetic treatment. M. roxburghianus treatment restores the antioxidant enzyme system and rejuvenates the islets mass in alloxanized rat by accelerating visfatin and PCNA expression in pancreatic tissue.

  18. Evaluation of Chromosomal Instability in Diabetic Rats Treated with Naringin

    PubMed Central

    A. Bakheet, Saleh; M. Attia, Sabry

    2011-01-01

    We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte chromosomal aberrations, and sperm characteristic assays to investigate the chromosomal instability in somatic and germinal cells of diabetic rats treated with multiple doses of naringin. The obtained results revealed that naringin was neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover, naringin significantly reduced the diabetes-induced chromosomal instability in somatic and germinal cells in a dose-dependent manner. In addition, diabetes induced marked biochemical alterations characteristic of oxidative stress including enhanced lipid peroxidation, accumulation of oxidized glutathione, reduction in reduced glutathione, and accumulation of intracellular reactive oxygen species. Treatment with naringin ameliorated these biochemical markers dose-dependently. In conclusion, naringin confers an appealing protective effect against diabetes-induced chromosomal instability towards rat somatic and germinal cells which might be explained partially via diminishing the de novo free radical generation induced by hyperglycemia. Thus, naringin might be a good candidate to reduce genotoxic risk associated with hyperglycemia and may provide decreases in the development of secondary malignancy and abnormal reproductive outcomes risks, which seems especially important for diabetic patients. PMID:21941606

  19. Topical fentanyl stimulates healing of ischemic wounds in diabetic rats

    PubMed Central

    FAROOQUI, Mariya; ERICSON, Marna E; GUPTA, Kalpna

    2016-01-01

    Background Topically applied opioids promote angiogenesis and healing of ischemic wounds in rats. We examined if topical fentanyl stimulates wound healing in diabetic rats by stimulating growth-promoting signaling, angiogenesis, lymphangiogenesis and nerve regeneration. Methods We used Zucker diabetic fatty rats that develop obesity and diabetes on a high fat diet due to a mutation in the Leptin receptor. Fentanyl blended with hydrocream was applied topically on ischemic wounds twice daily, and wound closure was analyzed regularly. Wound histology was analyzed by hematoxylin and eosin staining. Angiogenesis, lymphangiogenesis, nerve fibers and phospho-PDGFR-β were visualized by CD31-, lymphatic vessel endothelium-1, protein gene product 9.5- and anti-phospho PDGFR-β-immunoreactivity, respectively. Nitric oxide synthase (NOS) and PDGFR-β signaling were analyzed using Western immunoblotting. Results Fentanyl significantly promoted wound closure as compared to PBS. Histology scores were significantly higher in fentanyl-treated wounds, indicative of increased granulation tissue formation, reduced edema and inflammation, and increased matrix deposition. Fentanyl treatment resulted in increased wound angiogenesis, lymphatic vasculature, nerve fibers, nitric oxide, NOS and PDGFR-β signaling as compared to PBS. Phospho PDGFR-β co-localized with CD31 co-staining for vasculature. Conclusions Topically applied fentanyl promotes closure of ischemic wounds in diabetic rats. Increased angiogenesis, lymphangiogenesis, peripheral nerve regeneration, NO and PDGFR-β signaling are associated with fentanyl-induced tissue remodeling and wound healing. PMID:25266258

  20. Carvedilol Ameliorates Early Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Morsy, Mohamed A.; Ibrahim, Salwa A.; Amin, Entesar F.; Kamel, Maha Y.; Abdelwahab, Soha A.; Hassan, Magdy K.

    2014-01-01

    Diabetic nephropathy results in end-stage renal disease. On the other hand, carvedilol has been reported to have various pharmacological properties. The aim of this study therefore is to evaluate the possible protective effect of carvedilol on streptozotocin-induced early diabetic nephropathy and various mechanisms underlie this effect in rats. Single i.p. injection of streptozotocin (65 mg/kg) was administered to induce early diabetic nephropathy in Wistar rats. Oral administration of carvedilol at a dose level of 1 and 10 mg/kg daily for 4 weeks resulted in nephroprotective effect as evident by significant decrease in serum creatinine level, urinary albumin/creatinine ratio, and kidney index as well as renal levels of malondialdehyde, nitric oxide, tumor necrosis factor-α, and cyclooxygenase-2 with a concurrent increase in creatinine clearance and renal reduced glutathione level compared to diabetic untreated rats. The protective effect of carvedilol was confirmed by renal histopathological examination. The electron microscopic examination indicated that carvedilol could effectively ameliorate glomerular basement membrane thickening and podocyte injury. In conclusion, carvedilol protects rats against streptozotocin-induced early diabetic nephropathy possibly, in part, through its antioxidant as well as anti-inflammatory activities, and ameliorating podocyte injury. PMID:24991534

  1. Effect of All-Trans Retinoic Acid on the Pancreas of Streptozotocin-Induced Diabetic Rat.

    PubMed

    Eltony, Sohair A; Elmottaleb, Nashwa A; Gomaa, Asmaa M; Anwar, Mamdouh M; El-Metwally, Tarek H

    2016-03-01

    All-trans Retinoic acid (atRA) is instructive for the development of endocrine pancreas and is an integral component of β-cell induction protocols. We showed that atRA induces glucose-responsive endocrine transdifferentiation of pleomorphic pancreatic ductal adenocarcinoma cells in vitro. This study aimed to detect the role of atRA in improving the histological changes of the pancreas in diabetic rats. Forty young male Wistar rats were used and divided into three groups. Group I: normal vehicle control (N = 5). Group II: streptozotocin-induced diabetic rats (N = 20) were followed up at 0.0, 1, 2, and 4 weeks. Group III: streptozotocin-induced diabetic rats (N = 15) treated with atRA (2.5 mg/kg/day), were followed up at 1, 2, and 4 weeks. Specimens from the pancreas were processed for light, electron microscopy and pancreatic insulin mRNA expression. Blood samples were assayed for the levels of glucose, insulin, and total peroxides. In the atRA-treated group, the number of the islets and the islet area significantly increased. Strong insulin-immunoreactive endocrine-like cells were observed nearby the pancreatic acini and the interlobular ducts. Interestingly, insulin-positive cells seemed to arise from pancreatic acinar and ductal epithelium. Ultrastructurally, ß-cells, acinar, and ductal cells restored their normal appearance. Pancreatic insulin mRNA and blood indices were almost normalized. AtRA improved the histological changes of the pancreas and the blood indices in diabetic rats. © 2015 Wiley Periodicals, Inc.

  2. Effect of Urtica dioica Leaf Alcoholic and Aqueous Extracts on the Number and the Diameter of the Islets in Diabetic Rats

    PubMed Central

    Qujeq, Durdi; Tatar, Mohsen; Feizi, Farideh; Parsian, Hadi; Sohan Faraji, Alieh; Halalkhor, Sohrab

    2013-01-01

    Urtica dioica has been known as a plant that decreases blood glucose. Despite the importance of this plant in herbal medicine, relatively little research has been down on effects of this plant on islets yet. The objective of the current study was to evaluate the effect of dried Urtica dioica leaf alcoholic and aqueous extracts on the number and the diameter of the islets and histological parameters in streptozocin-induced diabetic rats. Six rats were used in each group. Group I: Normal rats were administered saline daily for 8 weeks. Group II: Diabetic rats were administered streptozotocin, 50 mg/kg of body weight; Group III: Diabetic rats were administered dried Urtica dioica leaf aqueous extracts for 8 weeks; Group IV: Diabetic rats were administered dried Urtica dioica leaf alcoholic extracts for 8 weeks. The animals, groups of diabetic and normal, were sacrificed by ether anaesthesia. Whole pancreas was dissected. The tissue samples were formalin fixed and paraffin embedded for microscopic examination. Histologic examination and grading were carried out on hematoxylin-eosin stained sections. The effects of administration of dried Urtica dioica leaf alcoholic and aqueous extracts to diabetic rats were determined by histopathologic examination. The pancreas from control rats showed normal pancreatic islets histoarchitecture. Our results also, indicate that the pancreas from diabetic rats show injury of pancreas tissue while the pancreas from diabetic rats treated with dried Urtica dioica leaf alcoholic and aqueous extracts show slight to moderate rearrangement of islets. According to our findings, dried Urtica dioica leaf alcoholic and aqueous extracts can cause a suitable repair of pancreatic tissue in streptozocin-induced diabetic experimental model. PMID:24551786

  3. Effect of Urtica dioica Leaf Alcoholic and Aqueous Extracts on the Number and the Diameter of the Islets in Diabetic Rats.

    PubMed

    Qujeq, Durdi; Tatar, Mohsen; Feizi, Farideh; Parsian, Hadi; Sohan Faraji, Alieh; Halalkhor, Sohrab

    2013-01-01

    Urtica dioica has been known as a plant that decreases blood glucose. Despite the importance of this plant in herbal medicine, relatively little research has been down on effects of this plant on islets yet. The objective of the current study was to evaluate the effect of dried Urtica dioica leaf alcoholic and aqueous extracts on the number and the diameter of the islets and histological parameters in streptozocin-induced diabetic rats. Six rats were used in each group. Group I: Normal rats were administered saline daily for 8 weeks. Group II: Diabetic rats were administered streptozotocin, 50 mg/kg of body weight; Group III: Diabetic rats were administered dried Urtica dioica leaf aqueous extracts for 8 weeks; Group IV: Diabetic rats were administered dried Urtica dioica leaf alcoholic extracts for 8 weeks. The animals, groups of diabetic and normal, were sacrificed by ether anaesthesia. Whole pancreas was dissected. The tissue samples were formalin fixed and paraffin embedded for microscopic examination. Histologic examination and grading were carried out on hematoxylin-eosin stained sections. The effects of administration of dried Urtica dioica leaf alcoholic and aqueous extracts to diabetic rats were determined by histopathologic examination. The pancreas from control rats showed normal pancreatic islets histoarchitecture. Our results also, indicate that the pancreas from diabetic rats show injury of pancreas tissue while the pancreas from diabetic rats treated with dried Urtica dioica leaf alcoholic and aqueous extracts show slight to moderate rearrangement of islets. According to our findings, dried Urtica dioica leaf alcoholic and aqueous extracts can cause a suitable repair of pancreatic tissue in streptozocin-induced diabetic experimental model.

  4. [Effects of lisinopril on diabetic peripheral neuropathy: experiment with rats].

    PubMed

    Han, Li-Ping; Yu, De-Min; Xie, Yun

    2008-09-16

    To investigate the effects of lisinopril, an angiotensin-converting enzyme inhibitor, on diabetic peripheral neuropathy (DNP). Twenty-five Wistar rats underwent intravenous injection of streptozocin to establish diabetes models and 10 rats were injected with sodium citrate solution as normal controls. The diabetic rats were randomly divided into 2 groups: lisinopril group treated with gastric perfusion of lisinopril daily for 8 weeks, and diabetic control group. The diabetic controls and normal controls were treated with gastric perfusion of water. Sciatic nerve electrode penetration method was used to measure the motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV). Light and heat pain measuring apparatus was used to measure the pain threshold. Then the sciatic nerves were isolated. Electron microscopy was used to observe the ultra-structure. The contents of superoxide dismutase (SOD) and malonyldialdehyde (MDA), and Na(+)K(+)-ATPase activity were detected by chemical colorimetry. Immunohistochemistry was used to detect the CD34 in the sciatic nerve. The capillary density of sciatic nerve was calculated. The MNCV and SNCV levels of the lisinopril group were both lower than those of the 2 control groups (all P < 0.01). The potency of heat pain leg retraction response of the lisinopril group was significantly shorter than that pf the diabetic control group (P < 0.05). The pathological changes of the lisinopril group were milder than those of the other groups. The SOD level and the Na(+)K(+)-ATPase activity of the diabetic group were significantly lower than those of the normal control group, and the MDA of the diabetic group was significantly higher than those of the other 2 groups (all P < 0.05). And the SOD level and Na(+)K(+)-ATPase activity of the lisinopril group were significantly higher than those of the diabetic control group, and the MDA level of the lisinopril group was significantly lower than that of the diabetic control

  5. Sulfur amino acid metabolism in Zucker diabetic fatty rats.

    PubMed

    Kwak, Hui Chan; Kim, Young-Mi; Oh, Soo Jin; Kim, Sang Kyum

    2015-08-01

    The present study was aimed to investigate the metabolomics of sulfur amino acids in Zucker diabetic fatty (ZDF) rats, an obese type 2 diabetic animal model. Plasma levels of total cysteine, homocysteine and methionine, but not glutathione (GSH) were markedly decreased in ZDF rats. Hepatic methionine, homocysteine, cysteine, betaine, taurine, spermidine and spermine were also decreased. There are no significant difference in hepatic S-adenosylmethionine, S-adenosylhomocysteine, GSH, GSH disulfide, hypotaurine and putrescine between control and ZDF rats. Hepatic SAH hydrolase, betaine-homocysteine methyltransferase and methylene tetrahydrofolate reductase were up-regulated while activities of gamma-glutamylcysteine ligase and methionine synthase were decreased. The area under the curve (AUC) of methionine and methionine-d4 was not significantly different in control and ZDF rats treated with a mixture of methionine (60mg/kg) and methionine-d4 (20mg/kg). Moreover, the AUC of the increase in plasma total homocysteine was comparable between two groups, although the homocysteine concentration curve was shifted leftward in ZDF rats, suggesting that the plasma total homocysteine after the methionine loading was rapidly increased and normalized in ZDF rats. These results show that the AUC of plasma homocysteine is not responsive to the up-regulation of hepatic BHMT in ZDF rats. The present study suggests that the decrease in hepatic methionine may be responsible for the decreases in its metabolites, such as homocysteine, cysteine, and taurine in liver and consequently decreased plasma homocysteine levels.

  6. Histological changes and antidiabetic activities of Icacina trichantha tuber extract in beta-cells of alloxan induced diabetic rats

    PubMed Central

    Monday, Onakpa Michael; Uzoma, Asuzu Isaac

    2013-01-01

    Objective To investigate the antidiabetic, hypolipidaemic activities and histopathological changes of Icacina trichantha (I. trichantha) tuber extract in alloxan induced diabetic rats. Methods In the present study, 80% methanol extract of I. trichantha tuber was tested on alloxan induced diabetic rats. They were randomly grouped into control (distilled water and glibenclamide) and experimental (200, 400 and 600 mg/kg body weight). Diabetes was induced by a single intraperitoneal injection of 160 mg/kg body weight of alloxan. Blood glucose levels were measured using blood glucose test strips with AccuCheck Advantage II glucometer at 1, 3, 6, and 24 h on the first day and 1 h after treatment on Day 7, 14 and 21. Blood samples were collected and centrifuged to separate serum for estimation of lipid profile and other biochemical parameters. Histopathological changes in diabetic rats pancreas were also studied after extract treatment. Results Daily oral administration of I. trichantha tuber extract (200, 400, and 600 mg/kg body weight) and glibenclamide (2 mg/kg) showed beneficial effects on blood glucose level (P<0.01) as well as improving liver, kidney functions and hyperlipidaemia due to diabetes. The extract had a favourable effect on the histopathological changes of the pancreas in alloxan induced diabetes. Conclusions I. trichantha tuber extracts posses antidiabetic activities as well as improve liver and renal profile and total lipids levels. I. trichantha tuber extracts also have favourable effects to inhibit the histopathological changes of the pancreas in alloxan induced diabetes. PMID:23905020

  7. Effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on streptozotocin-induced diabetic nephropathy.

    PubMed

    Sen, Saniye; Saniye, Sen; Kanter, Mehmet; Mehmet, Kanter; Ustundag, Sedat; Sedat, Ustundag; Aktas, Cevat; Cevat, Aktas; Dogutan, Haluk; Yalcin, Omer; Omer, Yalcin

    2008-01-01

    The aim of this study was designed to investigate the possible beneficial effects of the angiotensin-converting enzyme (ACE) inhibitor, Quinapril (Q) and, the angiotensin (ang) II T(1) (AT1) receptor blocker, irbesartan (Irb), in streptozotocin (STZ)-induced diabetes in rats. The rats were randomly allotted into one of five experimental groups: A (control), B (diabetic untreated), C (diabetic treated with Q), D (diabetic treated with Irb), and E (diabetic treated with Q&Irb), each group containing 10 animals. Groups B-E received STZ. Diabetes was induced in four groups by a single intraperitoneal (i.p) injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). Two days after STZ treatment, development of diabetes in four experimental groups was confirmed by measuring blood glucose levels in a tail vein blood samples. Rats with blood glucose levels of 250 mg/dL or higher were considered to be diabetic. The rats in Q-, Irb-, and Q&Irb-treated groups were given Q (in a dose of 3 mg/kg body weight), Irb (5 mg/kg body weight), and Q&Irb (in a dose of 1.5 mg/kg + 2.5 mg/kg body weight) once a day orally by using intra-gastric intubation for 12 weeks starting two days after STZ injection. Treatment of Q and especially Irb reduced the glomerular size and thickening of capsular, glomerular, and tubular basement membranes; and increased amounts of mesangial matrix and tubular dilatation and renal function as compared with diabetics untreated. Notably, the better effects were obtained when Q and Irb given together. We conclude that Q, Irb, and especially Q+Irb therapy causes renal morphologic and functional improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Q and Irb treatment, alone or its combination, may indicate its usefulness as a potential treatment in diabetic nephropathy (DNp).

  8. Morphologic and biomechanical changes of rat oesophagus in experimental diabetes

    PubMed Central

    Zeng, Yan-Jun; Yang, Jian; Zhao, Jing-Bo; Liao, Dong-Hua; Zhang, En-Ping; Gregersen, Hans; Xu, Xiao-Hu; Xu, Hong; Xu, Chuan-Qing

    2004-01-01

    AIM: To study morphologic and biomechanical changes of oesophagus in diabetes rats. METHODS: Diabetes was induced by a single injection of streptozotocin (STZ). The type of diabetes mellitus induced by parenteral STZ administration in rats was insulin-dependent (type I). The samples were excised and studied in vitro using a self-developed biomaterial test machine. RESULTS: The body mass was decreased after 4 d with STZ treatment. The length of esophagus shortened after 4, 7, 14 d. The opening angle increased after 14 d. The shear, longitudinal and circumferential stiffness were obviously raised after 28 d of STZ treatment. CONCLUSION: The changes of passive biomechanical properties reflect intra-structural alteration of tissue to a certain extent. This alteration will lead to some dysfunction of movement. For example, tension of esophageal wall will change due to some obstructive disease. PMID:15300896

  9. Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

    SciTech Connect

    Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

    2009-11-15

    Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

  10. Hepatoprotetive, Cardioprotective and Nephroprotective Actions of Essential Oil Extract of Artemisia sieberi in Alloxan Induced Diabetic Rats

    PubMed Central

    Irshaid, Fawzi; Mansi, Kamal; Bani-Khaled, Ahmad; Aburjia, Talal

    2012-01-01

    The aim of the current study is to evaluate the potential mechanism of antidiabetic action of the essential oil of Artemisia sieberi and its effects on some hematological and biochemical parameters in alloxan induced diabetic rats. Extraction of the essential oil from aerial parts of A. sieberi was preformed by hydrodistillation. Fifty rats were divided into five groups. Groups I and II normal rats given 1 mL/day of dimethyl sulfoxide and 80 mg/kg BW of this oil extract, respectively. Groups III, IV and V diabetic rats given 1 mL/day of dimethyl sulfoxide, oil extract (80 mg/kg BW) and metformin (14.2 mg/kg BW), respectively. Several hematological and biochemical parameters were assessed. Oral administration of the extract resulted in a significant reduction in the mean values of blood glucose, glucagon, cholesterol, triglyceride, LDL-C, ESR, urea, uric acid, creatinine accompanied by an increase in the mean values of the total protein, albumin, insulin, HDL-C, neutrophile count and PCV in diabetic rats. No significant changes in these parameters were found in the control group. The effects produced by this extract were closely similar to a standard antidiabetic drug, metformin. In conclusion, the present study indicates that the essential oil extract of A. sieberi appears to exhibit cardioprotective, nephroprotective and hepatoprotective activities in alloxan induced diabetic rats. PMID:24250557

  11. Increase of cardiac M2-muscarinic receptor gene expression in type-1 but not in type-2 diabetic rats.

    PubMed

    Lee, Liang-Ming; Chang, Cheng Kuei; Cheng, Kai-Chun; Kou, Dai-Huang; Liu, I-Min; Cheng, Juei-Tang

    2008-08-22

    Changes of cardiac M2-muscarinic receptor (M2-mAChR) gene expression was investigated in type-1 like diabetic rats induced by intravenous injection of streptozotocin (STZ) and type-2 like diabetic rats induced by fed with fructose-rich chow. Systolic blood pressure (SBP) in STZ-diabetic rats was significantly lower than that in age-matched non-diabetic rats, while the SBP in type-2 like diabetic rats was higher than in non-diabetic rats. Also, the mRNA or protein level of cardiac M2-mAChR in STZ-diabetic rats was markedly higher than non-diabetic rats, but it was not observed in type-2 like diabetic rats as compared to age-matched non-diabetic rats. Arecaidine propargyl ester (APE), the agonist of M2-mAChR, produced a marked reduction of heart rate in STZ-diabetic rats but made less influence on heart rate in fructose-fed rats or non-diabetic rats. The results suggest that cardiac M2-mAChR gene expression is raised in type-1 like diabetic rats but not in type-2 like diabetic rats, this difference mainly due to hyperglycemia, for the production of hypotension in diabetic disorders.

  12. Melatonin and succinate reduce rat liver mitochondrial dysfunction in diabetes.

    PubMed

    Zavodnik, I B; Lapshina, E A; Cheshchevik, V T; Dremza, I K; Kujawa, J; Zabrodskaya, S V; Reiter, R J

    2011-08-01

    Mitochondrial dysfunction and an increase in mitochondrial reactive oxygen species in response to hyperglycemia during diabetes lead to pathological consequences of hyperglycemia. The aim of the present work was to investigate the role of a specific functional damage in rat liver mitochondria during diabetes as well as to evaluate the possibility of metabolic and antioxidative correction of mitochondrial disorders by pharmacological doses of succinate and melatonin. In rat liver mitochondria, streptozotocin-induced diabetes was accompanied by marked impairments of metabolism: we observed a significant activation of α-ketoglutarate dehydrogenase (by 60%, p<0.05) and a damage of the respiratory function. In diabetic animals, melatonin (10 mg/kg b.w., 30 days) or succinate (50 mg/kg b.w., 30 days) reversed the oxygen consumption rate V(3) and the acceptor control ratio to those in nondiabetic animals. Melatonin enhanced the inhibited activity of catalase in the cytoplasm of liver cells and prevented mitochondrial glutathione-S-transferase inhibition while succinate administration prevented α-ketoglutarate dehydrogenase activation. The mitochondria dysfunction associated with diabetes was partially remedied by succinate or melatonin administration. Thus, these molecules may have benefits for the treatment of diabetes. The protective mechanism may be related to improvements in mitochondrial physiology and the antioxidative status of cells.

  13. Protective Effects of Fufang Xueshuantong on Diabetic Retinopathy in Rats

    PubMed Central

    Duan, Huihui; Huang, Jianmei; Li, Wei; Tang, Minke

    2013-01-01

    The aim of this study was to evaluate the protective effects of Fufang Xueshuantong (FXT) on diabetic retinopathy in rats induced by streptozotocin (STZ). Diabetes was induced in Sprague-Dawley rats by a single injection of 60 mg/kg STZ. One week after STZ, FXT 0.525 g/kg or 1.05 g/kg was administrated to the rats by intragastric gavage (ig) once daily consecutively for 24 weeks. The control rats and untreated STZ rats received vehicle the same way. At the end of the experiment, the erythrocyte aggregation and blood viscosity were assayed. The retina vessel morphology was observed in retinal digestive preparations. Expression of occludin and intercellular adhesion molecule-1 (ICAM-1) in retina was measured by western blotting. Expression of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in retina was detected by immunohistochemistry. The activity of aldose reductase in retina was investigated with a NADPH oxidation method. The results showed that, in STZ rats, there were distinct lesions in retinal vessel, including decrease of pericytes and increase of acellular capillaries, together with dilatation of retinal veins. The expression of VEGF and ICAM-1 increased, while the expression of PEDF and occludin decreased. The activity of aldose reductase elevated, and the whole blood viscosity, plasma viscosity, and erythrocyte aggregation also increased after STZ stimulation. FXT 0.525 g/kg and 1.05 g/kg demonstrated significant protective effects against STZ induced microvessel lesion in the retina with increased pericytes and reduced acellular capillaries. FXT also reduced the expression of VEGF and ICAM-1 and enhanced the expression of PEDF and occludin in STZ insulted rats. The activity of aldose reductase, the whole blood viscosity, plasma viscosity, and erythrocyte aggregation also decreased after FXT treatment. The results demonstrated that FXT has protective effect on STZ induced diabetic retinopathy in rats. PMID

  14. Carnosine treatment in combination with ACE inhibition in diabetic rats.

    PubMed

    Peters, V; Riedl, E; Braunagel, M; Höger, S; Hauske, S; Pfister, F; Zschocke, J; Lanthaler, B; Benck, U; Hammes, H-P; Krämer, B K; Schmitt, C P; Yard, B A; Köppel, H

    2014-11-01

    In humans, we reported an association of a certain allele of carnosinase gene with reduced carnosinase activity and absence of nephropathy in diabetic patients. CN1 degrades histidine dipeptides such as carnosine and anserine. Further, we and others showed that treatment with carnosine improves renal function and wound healing in diabetic mice and rats. We now investigated the effects of carnosine treatment alone and in combination with ACE inhibition, a clinically established nephroprotective drug in diabetic nephropathy. Male Sprague-Dawley rats were injected i.v. with streptozotocin (STZ) to induce diabetes. After 4 weeks, rats were unilaterally nephrectomized and randomized for 24 weeks of treatment with carnosine, lisinopril or both. Renal CN1 protein concentrations were increased under diabetic conditions which correlated with decreased anserine levels. Carnosine treatment normalized CN1 abundance and reduced glucosuria, blood concentrations of glycosylated hemoglobin (HbA1c), carboxyl-methyl lysine (CML), N-acetylglucosamine (GlcNac; all p<0.05 vs. non-treated STZ rats), reduced cataract formation (p<0.05) and urinary albumin excretion (p<0.05), preserved podocyte number (p<0.05) and normalized the increased renal tissue CN1 protein concentration. Treatment with lisinopril had no effect on HbA1C, glucosuria, cataract formation and CN1 concentration, but reduced albumin excretion rate more effectively than carnosine treatment (p<0.05). Treatment with both carnosine and lisinopril combined the effects of single treatment, albeit without additive effect on podocyte number or albuminuria. Increased CN1 amount resulted in decreased anserine levels in the kidney. Both carnosine and lisinopril exert distinct beneficial effects in a standard model of diabetic nephropathy. Both drugs administered together combine the respective effects of single treatment, albeit without exerting additive nephroprotection. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Candesartan augments compensatory changes in medullary transport proteins in the diabetic rat kidney

    PubMed Central

    Blount, Mitsi A.; Sands, Jeff M.; Kent, Kimilia J.; Smith, Tekla D.; Price, S. Russ; Klein, Janet D.

    2008-01-01

    Volume depletion due to persistent glucosuria-induced osmotic diuresis is a significant problem in uncontrolled diabetes mellitus (DM). Angiotensin II receptor blockers (ARBs), such as candesartan, slow the progression of chronic kidney disease in patients with DM. However, mice with genetic knockout of components of the renin-angiotensin system have urine concentrating defects, suggesting that ARBs may exacerbate the volume depletion. Therefore, the effect of candesartan on UT-A1, UT-A3, NKCC2, and aquaporin-2 (AQP2) protein abundances was determined in control and 3-wk DM rats. Aldosterone levels in control rats (0.36 ± 0.06 nM) and candesartan-treated rats (0.34 ± 0.14 nM) were the same. DM rats had higher aldosterone levels (1.48 ± 0.37 nM) that were decreased by candesartan (0.97 ± 0.26 nM). Western analysis showed that UT-A1 expression was increased in DM rats compared with controls in inner medullary (IM) tip (158 ± 13%) and base (120 ± 25%). UT-A3 abundance was increased in IM tip (123 ± 11%) and base (146 ± 17%) of DM rats vs. controls. UT-A3 was unchanged in candesartan-treated control rats. In candesartan-treated DM rats, UT-A3 increased in IM tip (160 ± 14%) and base (210 ± 19%). Candesartan-treated DM rats had slightly higher AQP2 in IM (46%, P < 0.05) vs. control rats. NKCC2/BSC1 was increased 145 ± 10% in outer medulla of DM vs. control rats. We conclude that candesartan augments compensatory changes in medullary transport proteins, reducing the losses of solute and water during uncontrolled DM. These changes may represent a previously unrecognized beneficial effect of type 1 ARBs in DM. PMID:18417538

  16. Effect of diabetic duration on hemorheological properties and platelet aggregation in streptozotocin-induced diabetic rats

    PubMed Central

    Yeom, Eunseop; Byeon, Hyeokjun; Lee, Sang Joon

    2016-01-01

    Diabetes mellitus with abnormal glucose concentration is associated with changes in hemorheological properties, endothelial function, and platelets hyperactivity. Disturbances may significantly be responsible for diabetes-related vascular complications. In this study, hemorheological and hemodynamic properties were measured according to diabetic duration after streptozotocin treatment in rats. For ex vivo measurements, an extracorporeal model was adopted. Flow rate and blood viscosity were measured using a microfluidic device. Erythrocyte aggregation and morphological parameters of erythrocytes were measured by modified erythrocyte sedimentation rate and the phase-contrast holography under in vitro conditions. The platelet aggregation and mean pressure in the femoral artery were estimated under ex vivo conditions. Hemorheological properties including blood viscosity, erythrocyte aggregation and shape parameters for the control group are significantly different with those for diabetic groups. The changes with respect to diabetic duration were relatively unnoticeable. However, the platelet aggregation is strongly dependent on the diabetic duration. Based on these results, hyperglycemia exposure may induce hemorheological variations in early stages of diabetes mellitus. High platelet aggregation may become more pronounced according to the diabetic duration caused by variations in hemorheological properties resulting in endothelial dysfunction. This study would be helpful in understanding the effects of diabetic duration on biophysical properties. PMID:26898237

  17. Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes

    PubMed Central

    Matsumoto, Yasuhiko; Ishii, Masaki; Hayashi, Yohei; Miyazaki, Shinya; Sugita, Takuya; Sumiya, Eriko; Sekimizu, Kazuhisa

    2015-01-01

    We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1 h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18 h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes. PMID:26024298

  18. Diabetic silkworms for evaluation of therapeutically effective drugs against type II diabetes.

    PubMed

    Matsumoto, Yasuhiko; Ishii, Masaki; Hayashi, Yohei; Miyazaki, Shinya; Sugita, Takuya; Sumiya, Eriko; Sekimizu, Kazuhisa

    2015-05-29

    We previously reported that sugar levels in the silkworm hemolymph, i.e., blood, increase immediately (within 1 h) after intake of a high-glucose diet, and that the administration of human insulin decreases elevated hemolymph sugar levels in silkworms. In this hyperglycemic silkworm model, however, administration of pioglitazone or metformin, drugs used clinically for the treatment of type II diabetes, have no effect. Therefore, here we established a silkworm model of type II diabetes for the evaluation of anti-diabetic drugs such as pioglitazone and metformin. Silkworms fed a high-glucose diet over a long time-period (18 h) exhibited a hyperlipidemic phenotype. In these hyperlipidemic silkworms, phosphorylation of JNK, a stress-responsive protein kinase, was enhanced in the fat body, an organ that functionally resembles the mammalian liver and adipose tissue. Fat bodies isolated from hyperlipidemic silkworms exhibited decreased sensitivity to human insulin. The hyperlipidemic silkworms have impaired glucose tolerance, characterized by high fasting hemolymph sugar levels and higher hemolymph sugar levels in a glucose tolerance test. Administration of pioglitazone or metformin improved the glucose tolerance of the hyperlipidemic silkworms. These findings suggest that the hyperlipidemic silkworms are useful for evaluating the hypoglycemic activities of candidate drugs against type II diabetes.

  19. Effect of telmisartan on VEGF-induced and VEGF-independent angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ)-induced diabetic rats.

    PubMed

    Chaudagar, Kiranj K; Mehta, Anita A

    2014-01-01

    Telmisartan possesses endothelial protective effects due to angiotensin II type 1 receptor antagonist, peroxisome proliferator-activated receptor γ (PPARγ) agonist and antioxidant action. Therefore, our objective was to study effect of telmisartan on angiogenic responsiveness of coronary endothelial cells (cECs) of normal and diabetic rats. Male Wistar rats were divided into six groups, normal rats, diabetic rats 30 d. (30 days after administration of STZ), diabetic rats 60 ds. (60 days after administration of STZ), telmisartan-treated normal rats (2 mg/kg, p.o., for 15 days before isolation of hearts), telmisartan-treated diabetic rats 30 ds, and telmisartan-treated diabetic rats 60 ds. Each group was further divided into two subgroups, sham rat hearts and ischemia-reperfused rat hearts. After isolation of cEC from each subgroup, angiogenic responsiveness and nitric oxide releasing properties were studied using chorioallantoic membrane (CAM) assay and Griess method, respectively. cEC of normal rats showed significant increase in angiogenic responsiveness in presence of vascular endothelial growth factor (VEGF) but not in absence of it. This activity was attenuated by pretreatment of cEC with l-NAME, wortmannin and chelerythrine. Diabetes and ischemia reperfusion injury suppressed angiogenic responsiveness of cEC. Telmisartan treatment showed significant increase in VEGF-induced angiogenic responsiveness and nitric oxide releasing properties of cECs of all subgroups as compared to their respective non-treated subgroups. These effects of telmisartan were significantly inhibited by pretreatment of cECs with L-NAME and wortmannin but not with chelerythrine. Our data suggest that telmisartan improves VEGF-induced coronary angiogenic activity in normal and diabetic rats via stimulation of PI3K/eNOS/NO pathway.

  20. Liver iron overload induced by tamoxifen in diabetic and non-diabetic female Wistar rats.

    PubMed

    Jatobá, Carlos André Nunes; de Rezende, Adriana Augusto; de Paiva Rodrigues, Sarah Jane; de Almeida Câmara, Maria Margareth; das Graças Almeida, Maria; Freire-Neto, Francisco; da Rocha, Luiz Reginaldo Menezes; da Medeiros, Aldo Cunha; Brandão-Neto, José; de Carvalho Formiga, Maria Célia; de Azevedo, Italo Medeiros; de Oliveira Ramos, Ana Maria

    2008-04-01

    Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin, Masson's trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism.

  1. [Diabetic foot risk in patients with type II diabetes mellitus in a family medicine unit].

    PubMed

    Márquez-Godínez, S A; Zonana-Nacach, A; Anzaldo-Campos, M C; Muñoz-Martínez, J A

    2014-01-01

    To determine the risk of diabetic foot in patients with type II diabetes mellitus (DM) seen in a Family Medicine Unit. The study included type II DM patients with a disease duration ≥ 5 years seen in a Family Medicine Unit, Tijuana, Mexico, during September-December 2011. Neuropathy was assessed with the Diabetic Neuropathy Symptom questionnaire, and pressure sensation using a 10-g Semmes-Weinstein monofilament. A patient had a high risk of diabetic foot if there was sensitivity loss, foot deformities, and non-palpable pedal pulses. We studied 205 patients with an average (± SD) age and DM duration of 59 ± 10 years and 10.7 ± 6.7 years, respectively. Ninety one patients (44%) had a high risk of developing diabetic foot, and it was associated with; an education of less than 6 years (OR 2.3; 95%CI: 1-1-4.1), DM disease duration ≥ 10 years (OR 5.1; 95%CI: 2.8-9.4), female gender (OR 2.0; 95%CI: 1.1-3.6), monthly familiar income <236 euros (OR 2.0; 95%CI: 1.1-3.8), and a glycosylated hemoglobin ≥ 7.0% (OR 2.8; 95%CI: 1.5-5.0). It is necessary that all DM patients seen in a family medicine clinic have a yearly screening for the early detection of diabetic neuropathy, since they have a high risk of diabetic foot. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  2. Molecular changes evoked by triethylenetetramine treatment in the extracellular matrix of the heart and aorta in diabetic rats.

    PubMed

    Gong, Deming; Lu, Jun; Chen, Xiuyin; Choong, Soon Y; Zhang, Shaoping; Chan, Yih-Kai; Glyn-Jones, Sarah; Gamble, Gregory D; Phillips, Anthony R J; Cooper, Garth J S

    2006-12-01

    Most patients with diabetes die from cardiac or arterial disease, for which there are limited therapeutic options. Free Cu(2+) ions are strongly pro-oxidant, and chelatable-Cu(II) is increased in the diabetic heart. We reported previously that treatment by Cu(II)-selective chelation with triethylenetetramine (TETA) evokes elevated urinary Cu(II) in diabetic rats and humans in whom it also improved hallmarks of established left ventricular (LV) disease. Here, we treated diabetic rats with TETA and evaluated its ability to ameliorate Cu(2+)-mediated LV and arterial damage by modifying the expression of molecular targets that included transforming growth factor (TGF)-beta1, Smad4, extracellular matrix (ECM) proteins, extracellular superoxide dismutase (EC-SOD), and heparan sulfate (HS). Eight-weeks of TETA treatment significantly improved cardiac diastolic function but not [glucose](plasma) in diabetic animals. LV and aortic mRNAs corresponding to TGF-beta1, Smad4, collagen types I, III, and IV, and fibronectin-1, and plasminogen activator inhibitor-1, were elevated in untreated diabetic animals and normalized after TETA treatment. EC-SOD mRNA and protein, and [HS](tissue) were significantly decreased in diabetes and restored by drug treatment. Candidate molecular mechanisms by which TETA could ameliorate diabetic cardiac and arteriovascular disease include the suppression of an activated TGF-beta/Smad signaling pathway that mediates increased ECM gene expression and restoration of normal EC-SOD and HS regulation. These findings are relevant to the restoration toward normal by TETA treatment of cardiac and arterial structure and function in diabetes.

  3. Diaphragmatic function is enhanced in fatty and diabetic fatty rats

    PubMed Central

    Carreira, Serge; Na, Na; Carillion, Aude; Jiang, Cheng; Beuvin, Maud; Lacorte, Jean-Marc; Bonnefont-Rousselot, Dominique; Riou, Bruno; Coirault, Catherine

    2017-01-01

    Background Obesity is associated with a decrease in mortality in the intensive care unit (ICU) (the "obesity paradox"). We hypothesized that obesity may paradoxically improve diaphragmatic function. Methods Diaphragm contractility was prospectively recorded in vitro in adult male Zucker lean (control), fatty, and diabetic fatty rats, at rest, after 12h mechanical ventilation and after fatigue. We analyzed diaphragm morphology, cytokines, and protein expression of the protein kinase signaling pathways. Results Diaphragm active-force (AF) was higher in fatty (96±7mN.mm-2,P = 0.02) but not in diabetic fatty rats (90±17mN.mm-2) when compared with controls (84±8mN.mm-2). Recovery from fatigue was improved in fatty and diabetic fatty groups compared with controls. Ventilator-induced diaphragmatic dysfunction was observed in each group, but AF remained higher in fatty (82±8mN.mm-2,P = 0.03) compared with controls (70±8mN.mm-2). There was neutral lipid droplet accumulation in fatty and diabetic fatty. There were shifts towards a higher cross-sectional-area (CSA) of myosin heavy chain isoforms (MyHC)-2A fibers in fatty and diabetic fatty compared with control rats (P = 0.002 and P<0.001, respectively) and a smaller CSA of MyHC-2X in fatty compared with diabetic fatty and control rats (P<0.001 and P<0.001, respectively). The phosphorylated total-protein-kinase-B (pAKT)/AKT ratio was higher in fatty (182±58%,P = 0.03), but not in diabetic fatty when compared with controls and monocarboxylate-transporter-1 was higher in diabetic fatty (147±36%,P = 0.04), but not in fatty. Conclusions Diaphragmatic force is increased in Zucker obese rats before and after mechanical ventilation, and is associated with activation of AKT pathway signaling and complex changes in morphology. PMID:28328996

  4. Early Treatment With Olmesartan Prevents Juxtamedullary Glomerular Podocyte Injury and the Onset of Microalbuminuria in Type 2 Diabetic Rats

    PubMed Central

    Sofue, Tadashi; Kiyomoto, Hideyasu; Kobori, Hiroyuki; Urushihara, Maki; Nishijima, Yoko; Kaifu, Kumiko; Hara, Taiga; Matsumoto, Sachiko; Ichimura, Atsuhiko; Ohsaki, Hiroyuki; Hitomi, Hirofumi; Kawachi, Hiroshi; Hayden, Melvin R.; Whaley-Connell, Adam; Sowers, James R.; Ito, Sadayoshi; Kohno, Masakazu; Nishiyama, Akira

    2012-01-01

    Background Studies were performed to determine if early treatment with an angiotensin II (Ang II) receptor blocker (ARB), olmesartan, prevents the onset of microalbuminuria by attenuating glomerular podocyte injury in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes mellitus. Methods OLETF rats were treated with either a vehicle, olmesartan (10 mg/kg/day) or a combination of nonspecific vasodilators (hydralazine 15 mg/kg/day, hydrochlorothiazide 6 mg/kg/day, and reserpine 0.3 mg/kg/day; HHR) from the age of 7–25 weeks. Results OLETF rats were hypertensive and had microalbuminuria from 9 weeks of age. At 15 weeks, OLETF rats had higher Ang II levels in the kidney, larger glomerular desmin-staining areas (an index of podocyte injury), and lower gene expression of nephrin in juxtamedullary glomeruli, than nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. At 25 weeks, OLETF rats showed overt albuminuria, and higher levels of Ang II in the kidney and larger glomerular desmin-staining areas in superficial and juxtamedullary glomeruli compared to LETO rats. Reductions in mRNA levels of nephrin were also observed in superficial and juxtamedullary glomeruli. Although olmesartan did not affect glucose metabolism, it decreased blood pressure and prevented the renal changes in OLETF rats. HHR treatment also reduced blood pressure, but did not affect the renal parameters. Conclusions This study demonstrated that podocyte injury occurs in juxtamedullary glomeruli prior to superficial glomeruli in type 2 diabetic rats with microalbuminuria. Early treatment with an ARB may prevent the onset of albuminuria through its protective effects on juxtamedullary glomerular podocytes. PMID:22318512

  5. Protective effects of sodium selenite on lead nitrate-induced hepatotoxicity in diabetic and non-diabetic rats.

    PubMed

    Kalender, Suna; Apaydin, Fatma Gökçe; Baş, Hatice; Kalender, Yusuf

    2015-09-01

    In the present study, the effect of sodium selenite on lead induced toxicity was studied in Wistar rats. Sodium selenite and lead nitrate were administered orally for 28 days to streptozotocin induced diabetic and non-diabetic rats. Eight groups of rats were used in the study: control, sodium selenite, lead nitrate, lead nitrate+sodium selenite, streptozotocin-induced diabetic-control, diabetic-sodium selenite, diabetic-lead nitrate, diabetic-lead nitrate+sodium selenite groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in liver tissues were investigated in all groups. There were statistically significant changes in liver function tests, antioxidant enzyme activities and lipid peroxidation levels in lead nitrate and sodium selenite+lead nitrate treated groups, also in diabetic and non-diabetic groups. Furthermore, histopathological alterations were demonstrated in same groups. In the present study we found that sodium selenite treatment did not show completely protective effect on diabetes mellitus caused damages, but diabetic rats are more susceptible to lead toxicity than non-diabetic rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Antihyperglycaemic effect of laser acupuncture treatment at BL20 in diabetic rats.

    PubMed

    Cornejo-Garrido, Jorge; Becerril-Chávez, Flavia; Carlín-Vargas, Gabriel; Ordoñez-Rodríguez, Juan Manuel; Abrajan-González, María Del Carmen; de la Cruz-Ramírez, Rosario; Ordaz-Pichardo, Cynthia

    2014-12-01

    To investigate the antihyperglycaemic activity of laser acupuncture stimulation at 650 and 980 nm at BL20 in streptozotocin (STZ)-induced diabetic rats. Seventy healthy adult male albino Wistar rats weighing 250±50 g were divided into seven groups of 10 animals each. Groups I-III comprised healthy control rats which were untreated (I) or stimulated with laser acupuncture at 650 nm (II) and 980 nm (III), respectively. Groups IV-VII underwent induction of diabetes with a single intraperitoneal administration of STZ at 50 mg/kg. Animals with blood glucose levels of ≥200 mg/dL on the fifth day were used for the experiments and were left untreated (group IV), treated with glibenclamide (group V) or stimulated with laser acupuncture at 650 nm (group VI) and 980 nm (group VII), respectively. Laser acupuncture was applied at BL20 on alternate days for a total of 12 sessions over a 28-day period. After 28 days of treatment, STZ-induced diabetic rats stimulated with laser acupuncture at 650 and 980 nm had significantly lower glucose levels compared with untreated diabetic rats (242.0±65.0 and 129.8±33.2 vs 376.5±10.0 mg/dL, both p≤0.05). Treatment at 980 nm also attenuated the increase in glucose between day 1 and day 28 compared with the glibenclamide-treated diabetic group (41.5±19.6 mg/dL vs 164.1±13.7 g/dL, p<0.05). Laser acupuncture treatment did not affect the blood count or biochemical profile and was not associated with any morphological changes in the pancreas, liver, kidney or spleen. Stimulation with laser acupuncture at 650 and 980 nm at BL20 in STZ-induced diabetic rats has antihyperglycaemic activity. The results support further evaluation of laser acupuncture as an alternative or complementary treatment for the control of hyperglycaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Hypoglycemic effect of syringin from Eleutherococcus senticosus in streptozotocin-induced diabetic rats.

    PubMed

    Niu, Ho-Shan; Liu, I-Min; Cheng, Juei-Tang; Lin, Che-Ling; Hsu, Feng-Lin

    2008-02-01

    Eleutherococcus senticosus (Araliaceae ) is a very powerful adaptogenic agent. In the present study, the effects of syringin, an active principle of this herb, on plasma glucose levels in streptozotocin-induced diabetic rats (STZ-diabetic rats) were investigated. Thirty minutes after syringin was intravenously injected into fasting STZ-diabetic rats, plasma glucose levels dose-dependently decreased. In normal rats, syringin at the effective dose (1.0 mg/kg) significantly attenuated the increase in plasma glucose caused by an intravenous glucose challenge. Syringin dose-dependently (0.01 to 10.0 micromol/L) stimulated glucose uptake in soleus muscle isolated from STZ-diabetic rats. Syringin treatment of hepatocytes isolated from STZ-diabetic rats enhanced glycogen synthesis . The ability of syringin to enhance glucose utilization and lower plasma glucose level in rats suffering from insulin deficiency suggest that this chemical may be useful in the treatment of human diabetes.

  8. Preventive effects of Morus alba L. anthocyanins on diabetes in Zucker diabetic fatty rats

    PubMed Central

    SARIKAPHUTI, ARIYA; NARARATWANCHAI, THAMTHIWAT; HASHIGUCHI, TERUTO; ITO, TAKASHI; THAWORANUNTA, SITA; KIKUCHI, KIYOSHI; OYAMA, YOKO; MARUYAMA, IKURO; TANCHAROEN, SALUNYA

    2013-01-01

    The mulberry plant (Morus alba L.) contains abundant anthocyanins (ANCs), which are natural antioxidants. The aim of this study was to determine the ANC composition of Thai Morus alba L. fruits and to assess the effect of an ANC extract on blood glucose and insulin levels in male leptin receptor-deficient Zucker diabetic fatty (ZDF) rats. The major components of the ANC extract were identified by high-performance liquid chromatography-electrospray ionization-mass spectrometry. ZDF and lean rats were treated with 125 or 250 mg ANCs/kg body weight, or 1% carboxymethylcellulose (CMC) twice daily for 5 weeks. Neither ANC dose had an effect on body weight. Following 5 weeks of treatment, glucose levels were observed to increase from 105.5±8.7 to 396.25±21 mg/dl (P<0.0001) in the CMC-treated ZDF rats; however, the glucose levels were significantly lower in the rats treated with 125 or 250 mg/kg ANCs (228.25±45 and 131.75±10 mg/dl, respectively; P<0.001 versus CMC). The administration of 250 mg/kg ANCs normalized glucose levels in the ZDF rats towards those of the lean littermates. Insulin levels were decreased significantly in the ZDF rats treated with CMC or 125 mg/kg ANCs (P<0.0001), but not in the rats treated with 250 mg/kg ANCs. Histologically, 250 mg/kg ANCs was observed to prevent islet degeneration compared with the islets in CMC-treated rats. This study, demonstrated that ANCs extracted from Morus alba L. were well tolerated and exhibited effective anti-diabetic properties in ZDF rats. ANCs represent a promising class of therapeutic compounds that may be useful in the prevention of type 2 diabetes. PMID:24137248

  9. Effect of repeated stress in early childhood on the onset of diabetes mellitus in male Spontaneously Diabetic Torii rats.

    PubMed

    Ookawa, Katumasa; Mochizuki, Kazuo; Yokogoshi, Hidehiko

    2008-02-01

    Spontaneously Diabetic Torii (SDT) rats were discovered from SD rats and represent a confirmed spontaneous type 2 diabetes mellitus model. We investigated the effect of repeated stress in early childhood on SDT rats fed a high-fat diet, on locomotor activity and on the onset of diabetes mellitus. Regarding stress, a water immersion-restraint stress (WIRS) burden was applied 10 times every other day from 4 weeks of age. The results of the study showed, that the locomotor activity of the young SDT rats was clearly lower than that of the SD rats, and their locomotor activity was inferred to be congenitally low. In addition, the stress-burdened SDT rats showed delayed onset of diabetes mellitus and impaired glucose tolerance compared with the rats not receiving stress burden. The locomotor activity of SDT rats is less than that of SD rats, and they SDT rats are thought to have poor at spontaneous energy expenditure. On the other hand, the feeding efficiency of the WIRS-burdened SDT rats was reduced, and in comparison with the SDT rats with no WIRS burden, energy expenditure was increased; this is suggested to influence the onset of diabetes mellitus.

  10. The influence of dietary Cu and diabetes on tissue sup 67 Cu retention kinetics in rats

    SciTech Connect

    Uriu-Hare, J.Y.; Rucker, R.B.; Keen, C.L. )

    1991-03-11

    Compared to controls, diabetes results in higher plasma, liver and kidney Cu concentrations. Since alterations in Cu metabolism may be associated with diabetic pathology, the authors investigated how Cu metabolism is affected by diabetes and dietary Cu intake. Nondiabetic and STZ diabetic rats were fed Cu suppl. or Cu def. diets for 5 wks. Rats were intubated with 28 {mu}Ci {sup 67}Cu and killed after 8, 16, 24, 32, 64, or 128 h. There were marked effects of both diet and diabetes on {sup 67}Cu metabolism. Independent of diabetes, deficient rats had a higher % of retained {sup 67}Cu, in liver, plasma, RBC, muscle, spleen, brain, lung, uterus, and intestine than adequate Cu rats. Independent of dietary Cu, diabetic rats had a lower % of retained {sup 67}Cu in liver, plasma, RBC, muscle, spleen, lung, bone, pancreas, skin, uterus and heart than controls. Differential effects were noted for kidney; adequate Cu diabetic rats had a higher % of retained {sup 67}Cu than all other groups. Marked effects of both diet and diabetes were evident when tissue Cu turnover was examined. Compared to Cu suppl. rats, Cu def. rats had a slower turnover of {sup 67}Cu, in liver, plasma, intestine, pancreas, eye, brain, muscle, spleen, lung and heart. Diabetic rats had a slower turnover of {sup 67}Cu than nondiabetic rats in liver, plasma, intestine, pancreas, eye, kidney, RBC and uterus. The data imply that a focus on Cu metabolism with regard to cellular Cu trafficking and pathology may be warranted.

  11. Zn(II) transport and distribution in rat spermatids.

    PubMed

    Reyes, J G; Arrate, M P; Santander, M; Guzman, L; Benos, D J

    1993-10-01

    Zn(II) is an essential trace element. In spermatozoa, Zn(II) modulates metabolism and chromatin condensation. The mechanisms of uptake and distribution of this ion in sperm cells have not been explored. In rat spermatids, our results indicate that 1) 65Zn(II) binds with fast kinetics to a labile, presumably extracellular, compartment. This binding is temperature insensitive and not modified by metabolic inhibitors. 2) Entry of 65Zn(II) in the absence of externally added proteins occurs through a mediated transport system that allows exchange to reach steady state in approximately 15 min at 34 degrees C. 3) Upon entering the cells, 65Zn(II) binds tightly to cellular organelles. 4) Exchangeable Zn(II) bound to cytoplasmic proteins plus free intracellular Zn(II) appears to be < 20% of total exchangeable Zn(II). 5) The intracellular exchangeable Zn(II) compartment is decreased by metabolic inhibitors, showing a direct or indirect link between energy metabolism and cellular Zn(II) levels. 6) 65Zn(II) efflux from rat spermatids is a process with a rate constant of 0.16 +/- 0.13 min-1 at 34 degrees C. This exit rate of Zn(II) is likely to be affected by Zn(II) release from cytoplasmic binding sites or organelles.

  12. Pharmacological Evaluation of Chrozophora tinctoria as Wound Healing Potential in Diabetic Rat's Model

    PubMed Central

    Semwal, Monika; Dubey, Susheel Kumar

    2016-01-01

    Objective. The study was designed to evaluate pharmacological potential of hydroalcoholic leaves extract of Chrozophora tinctoria intended for wound healing in diabetic rats' model. Methods. The method used to evaluate the pharmacological potential of hydroalcoholic leave extract was physical incision rat model. In this model, cutting of the skin and/or other tissues with a sharp blade has been made and the rapid disruption of tissue integrity with minimal collateral damage was observed shortly. Animals used in the study were divided into four groups that consist of six animals in each group. Group I serves as normal control, Group II serves as disease control, Group III was used as standard treatment (Povidone iodine 50 mg/kg b.w.), and Group IV was used for test drug (C. tinctoria 50 mg/kg b.w.). Result. The hydroalcoholic leave extract of Chrozophora tinctoria has been significantly observed to heal the wound (98%) in diabetic rats within 21 days, while standard drug (Povidone iodine) healed the wound about 95% in the same condition. The oral dose (50 mg/kg b.w.) of Chrozophora tinctoria was also found to improve the elevated blood glucose level in comparison to disease control group, which increased after the oral administration of Streptozotocin. Conclusion. The Chrozophora tinctoria has significant wound healing potential in the animal having physically damaged tissue in diabetic condition. PMID:28097147

  13. Metformin restores endothelial function in aorta of diabetic rats

    PubMed Central

    Sena, Cristina M; Matafome, Paulo; Louro, Teresa; Nunes, Elsa; Fernandes, Rosa; Seiça, Raquel M

    2011-01-01

    BACKGROUND AND PURPOSE The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been fully elucidated. This study was designed to assess the effect of metformin on impaired endothelial function, oxidative stress, inflammation and advanced glycation end products formation in type 2 diabetes mellitus. EXPERIMENTAL APPROACH Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes, fed with normal and high-fat diet during 4 months were treated with metformin for 4 weeks before evaluation. Systemic oxidative stress, endothelial function, insulin resistance, nitric oxide (NO) bioavailability, glycation and vascular oxidative stress were determined in the aortic rings of the different groups. A pro-inflammatory biomarker the chemokine CCL2 (monocyte chemoattractant protein-1) was also evaluated. KEY RESULTS High-fat fed GK rats with hyperlipidaemia showed increased vascular and systemic oxidative stress and impaired endothelial-dependent vasodilatation. Metformin treatment significantly improved glycation, oxidative stress, CCL2 levels, NO bioavailability and insulin resistance and normalized endothelial function in aorta. CONCLUSION AND IMPLICATIONS Metformin restores endothelial function and significantly improves NO bioavailability, glycation and oxidative stress in normal and high-fat fed GK rats. This supports the concept of the central role of metformin as a first-line therapeutic to treat diabetic patients in order to protect against endothelial dysfunction associated with type 2 diabetes mellitus. PMID:21250975

  14. Hydrogen sulfide alleviates diabetic nephropathy in a streptozotocin-induced diabetic rat model.

    PubMed

    Zhou, Xiang; Feng, Yu; Zhan, Zhoubing; Chen, Jianchang

    2014-10-17

    Accumulating evidence has demonstrated that hydrogen sulfide (H2S) plays critical roles in the pathogenesis of chronic kidney diseases. This study was designed to investigate whether H2S has protective effects against diabetic nephropathy. Diabetic rats were induced by intraperitoneal injection of streptozotocin and administrated with H2S donor NaHS for 12 weeks. Rat glomerular mesangial cells were pretreated with NaHS or MAPK inhibitors (U0126, SP600125, and SB203580) prior to high glucose exposure, and cell proliferation was determined. Our findings suggest that H2S can improve renal function and attenuate glomerular basement membrane thickening, mesangial matrix deposition, and renal interstitial fibrosis in diabetic rats. H2S was found to reduce high glucose-induced oxidative stress by activating the Nrf2 antioxidant pathway and to exert anti-inflammatory effects by inhibiting NF-κB signaling. In addition, H2S reduced high glucose-induced mesangial cell proliferation by blockade of MAPK signaling pathways. Moreover, H2S was also found to inhibit the renin-angiotensin system in diabetic kidney. In conclusion, our study demonstrates that H2S alleviates the development of diabetic nephropathy by attenuating oxidative stress and inflammation, reducing mesangial cell proliferation, and inhibiting renin-angiotensin system activity.

  15. Calcium dobesilate attenuates vascular injury and the progression of diabetic retinopathy in streptozotocin-induced diabetic rats.

    PubMed

    Padilla, Eugenia; Ganado, Patricia; Sanz, Mercedes; Zeini, Miriam; Ruiz, Emilio; Triviño, Alberto; Ramírez, Ana I; Salazar, Juan J; Ramírez, Jose M; Rojas, Blanca; Hoz, Rosa de; Tejerina, Teresa

    2005-01-01

    Diabetic retinopathy (DR) is a highly specific vascular complication of type 1 and type 2 diabetes mellitus. Calcium dobesilate (DOBE) has been tested in the treatment of diabetic retinopathy showing a slowdown of the progression of the disease after long-term oral treatment. The aim of this study was to determine the effects of DOBE on vascular and diabetic retinopathy in streptozotocin (STZ) diabetic rats. Diabetes was induced in wistar rats by the administration of STZ (60 mg/kg, i.p.). Rats were divided into three groups (n = 30). Group 0 (GO): nondiabetic rats. Group 1 (G1): 14 months of insulin treatment after diabetes development. Group 2 (G2): 14 months of insulin treatment after diabetes development plus DOBE (500 mg/kg/day). At the end of the treatment, vascular reactivity was tested. The study of the vascularization of the retina was performed on wholemounts of trypsin retinal digest preparations and retinal sections. Relaxation induced by acetylcholine decreased in the aorta arteries from diabetic rats but it was restored to control values in the DOBE-treated group (71.8 +/- 4.5%, 53.3 +/- 0.5%, 67.4 +/- 4.6% in group 0, 1 and 2 respectively). DOBE treatment also restored noradrenaline (1.08 +/- 0.05 g, 1.70 +/- 0.08 g, 1.13 +/- 0.05 g in group 0, 1 and 2 respectively) and caffeine-induced contractions. Diabetic state did not cause any alteration in mesenteric arteries. The analysis of the retinal digests showed vascular tortuosity, acellular capillaries, focal accumulations of capillaries and reduction of the number of pericytes in G1. The vascular changes observed in G2 seem to be intermediate between the control and the diabetic rats. We showed that long-term treatment with DOBE attenuated the progression of diabetic retinopathy and the alterations in vascular reactivity in streptozotocin-induced diabetic rats. Copyright 2004 John Wiley & Sons, Ltd.

  16. Effects of decompression on behavioral, electrophysiologic, and histomorphologic recovery in a chronic sciatic nerve compression model of streptozotocin-induced diabetic rats

    PubMed Central

    Wang, Ping-Hui; Yang, Cheng-Chang; Su, Wei-Ren; Wu, Po-Ting; Cheng, Shun-Chien; Jou, I-Ming

    2017-01-01

    Purpose To determine susceptibility to decompression surgery in diabetic and nondiabetic peripheral neuropathy using a chronic compression neuropathy model. Materials and methods Twenty-four streptozotocin-induced diabetic rats were randomly divided into three groups: group I, chronic compression of the left sciatic nerve for 4 weeks with decompression; group II, similar without decompression; and group III, sham exposing the sciatic nerve only. The other 24 nondiabetic rats were assigned to groups IV–VI, which received compression–decompression, compression, and the sham operation, respectively. Mixed-nerve-elicited somatosensory evoked potentials (M-SSEPs) and compound muscle action potentials (CMAPs) were measured to verify the compression neuropathy in the posttreatment follow-up. Behavioral observations in thermal hyperalgesia tests were quantified before electrophysiologic examinations. Treated and contralateral nerves were harvested for histomorphologic analysis. Results Chronic compression of sciatic nerve induced significant reduction of amplitude and increment of latency of M-SSEP and CMAP in both diabetic and nondiabetic rats. Diabetic group changes were more susceptible. Decompression surgery significantly improved both sensory and motor conduction, thermal hyperalgesia, and the mean myelin diameter of the rat sciatic nerve in both diabetic and nondiabetic groups. Near full recovery of motor and sensory function occurred in the nondiabetic rats, but not in the diabetic rats 8 weeks postdecompression. Conclusion Behavioral, electrophysiologic, and histomorphologic findings indicate that decompression surgery is effective in both diabetic and nondiabetic peripheral neuropathy. PMID:28360533

  17. Dynamic aerobic exercise induces baroreflex improvement in diabetic rats.

    PubMed

    Jorge, Luciana; da Pureza, Demilto Y; da Silva Dias, Danielle; Conti, Filipe Fernandes; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2012-01-01

    The objective of the present study was to investigate the effects of an acute aerobic exercise on arterial pressure (AP), heart rate (HR), and baroreflex sensitivity (BRS) in STZ-induced diabetic rats. Male Wistar rats were divided into control (n = 8) and diabetic (n = 8) groups. AP, HR, and BRS, which were measured by tachycardic and bradycardic (BR) responses to AP changes, were evaluated at rest (R) and postexercise session (PE) on a treadmill. At rest, STZ diabetes induced AP and HR reductions, associated with BR impairment. Attenuation in resting diabetes-induced AP (R: 103 ± 2 versus PE: 111 ± 3 mmHg) and HR (R: 290 ± 7 versus PE: 328 ± 10 bpm) reductions and BR dysfunction (R: -0.70 ± 0.06 versus PE: -1.21 ± 0.09 bpm/mmHg) was observed in the postexercise period. In conclusion, the hemodynamic and arterial baro-mediated control of circulation improvement in the postexercise period reinforces the role of exercise in the management of cardiovascular risk in diabetes.

  18. Dynamic Aerobic Exercise Induces Baroreflex Improvement in Diabetic Rats

    PubMed Central

    Jorge, Luciana; da Pureza, Demilto Y.; Dias, Danielle da Silva; Conti, Filipe Fernandes; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2012-01-01

    The objective of the present study was to investigate the effects of an acute aerobic exercise on arterial pressure (AP), heart rate (HR), and baroreflex sensitivity (BRS) in STZ-induced diabetic rats. Male Wistar rats were divided into control (n = 8) and diabetic (n = 8) groups. AP, HR, and BRS, which were measured by tachycardic and bradycardic (BR) responses to AP changes, were evaluated at rest (R) and postexercise session (PE) on a treadmill. At rest, STZ diabetes induced AP and HR reductions, associated with BR impairment. Attenuation in resting diabetes-induced AP (R: 103 ± 2 versus PE: 111 ± 3 mmHg) and HR (R: 290 ± 7 versus PE: 328 ± 10 bpm) reductions and BR dysfunction (R: −0.70 ± 0.06 versus PE: −1.21 ± 0.09 bpm/mmHg) was observed in the postexercise period. In conclusion, the hemodynamic and arterial baro-mediated control of circulation improvement in the postexercise period reinforces the role of exercise in the management of cardiovascular risk in diabetes. PMID:22203833

  19. Effects of chlorogenic acid, caffeine and coffee on components of the purinergic system of streptozotocin-induced diabetic rats.

    PubMed

    Stefanello, Naiara; Schmatz, Roberta; Pereira, Luciane Belmonte; Cardoso, Andréia Machado; Passamonti, Sabina; Spanevello, Rosélia Maria; Thomé, Gustavo; de Oliveira, Giovanna Medeiros Tavares; Kist, Luiza Wilges; Bogo, Maurício Reis; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

    2016-12-01

    We evaluated the effect of chlorogenic acid (CGA), caffeine (CA) and coffee (CF) on components of the purinergic system from the cerebral cortex and platelets of streptozotocin-induced diabetic rats. Animals were divided into eight groups: control animals treated with (I) water (WT), (II) CGA (5 mg/kg), (III) CA (15 mg/kg) and (IV) CF (0.5 g/kg), and diabetic animals treated with (V) WT, (VI) CGA (5 mg/kg), (VII) CA (15 mg/kg) and (VIII) CF (0.5 g/kg). Our results showed an increase (173%) in adenosine monophosphate (AMP) hydrolysis in the cerebral cortex of diabetic rats. In addition, CF treatment increased adenosine diphosphate (ADP) and AMP hydrolysis in group VIII synaptosomes. Platelets showed an increase in ectonucleotidase activity in group V, and all treatments reduced the increase in adenosine triphosphate and ADP hydrolysis. Furthermore, there was an increase in platelet aggregation of 72% in the diabetic rats, and CGA and CF treatment reduced platelet aggregation by nearly 60% when compared to diabetic rats. In this context, we can suggest that CGA and CF treatment should be considered a therapeutic and scientific target to be investigated in diseases associated with hyperglycemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Pharmacological Evaluation of “Sugar Remedy,” A Polyherbal Formulation, on Streptozotocin-Induced Diabetic Mellitus in Rats

    PubMed Central

    Singhal, Sandeep; Rathore, Arvind Singh; Lohar, Vikram; Dave, Rakesh; Dave, Jeetesh

    2014-01-01

    In the present study, Sugar Remedy, a polyherbal formulation (manufactured by Umalaxmi Organics Pvt Ltd, Jodhpur, Rajasthan, India) was evaluated for its antihyperglycemic, antihyperlipidemic, and antioxidant effects against normal and streptozotocin (STZ)-induced diabetic rats. Type II diabetes was induced in male Wistar rats by administration of a single intraperitoneal (IP) injection of STZ at a dose of 60 mg/kg. Effects of three different doses of Sugar Remedy suspension (185, 370, and 740 mg/kg/day, orally) and Metformin (500 mg/kg/day, orally) administered for 21 days were studied on parameters such as blood glucose, lipid profile, and antioxidant levels. Results were analyzed using one-way analysis of variance (ANOVA) followed by Dunnett's test. No significant changes were noticed in blood glucose, serum lipid levels, and kidney parameters in normal rats treated with Sugar Remedy suspension alone. The efficacy of Sugar Remedy as an antihyperglycemic, antihyperlipidemic, and antioxidant agent in STZ-induced diabetes was comparable to that of the standard, 500 mg/kg of Metformin. Present findings provide experimental evidence that Sugar Remedy has significant antihyperglycemic, antihyperlipidemic, and antioxidative effects in diabetic experimental rats. Hence, Sugar Remedy may be regarded as a promising natural and safe remedy for the prevention or delay of diabetic complications. PMID:25161924

  1. Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats.

    PubMed

    Agil, Ahmad; El-Hammadi, Mazen; Jiménez-Aranda, Aroa; Tassi, Mohamed; Abdo, Walied; Fernández-Vázquez, Gumersindo; Reiter, Russel J

    2015-08-01

    Hepatic mitochondrial dysfunction is thought to play a role in the development of liver steatosis and insulin resistance, which are both common characteristics of obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the antioxidant properties of melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg BW/day) orally for 6 wk (M-ZDF and M-ZL) or vehicle as control groups (C-ZDF and C-ZL). Hepatic function was evaluated by measurement of serum alanine transaminase and aspartate transaminase levels, liver histopathology and electron microscopy, and hepatic mitochondrial functions. Several impaired functions of hepatic mitochondria were observed in C-ZDF in comparison with C-ZL rats. Melatonin treatment to ZDF rats decreases serum levels of ALT (P < 0.001), alleviates liver steatosis and vacuolation, and also mitigates diabetic-induced mitochondrial abnormalities, glycogen, and lipid accumulation. Melatonin improves mitochondrial dysfunction in M-ZDF rats by increasing activities of mitochondrial citrate synthase (P < 0.001) and complex IV of electron transfer chain (P < 0.05) and enhances state 3 respiration (P < 0.001), respiratory control index (RCR) (P < 0.01), and phosphorylation coefficient (ADP/O ratio) (P < 0.05). Also melatonin augments ATP production (P < 0.05) and diminishes uncoupling protein 2 levels (P < 0.001). These results demonstrate that chronic oral melatonin reduces liver steatosis and mitochondria dysfunction in ZDF rats. Therefore, it may be beneficial in the treatment of diabesity.

  2. Neurturin and a Glp-1 Analogue Act Synergistically to Alleviate Diabetes in Zucker Diabetic Fatty Rats.

    PubMed

    Trevaskis, James L; Sacramento, Chester Bittencourt; Jouihan, Hani; Ali, Safina; Le Lay, John; Oldham, Stephanie; Bhagroo, Nicholas; Boland, Brandon B; Cann, Jennifer; Chang, Yuan; O'Day, Terrence; Howard, Victor; Reers, Christina; Winzell, Maria Sorhede; Smith, David M; Feigh, Michael; Barkholt, Pernille; Schreiter, Kay; Austen, Matthias; Andag, Uwe; Thompson, Simon; Jermutus, Lutz; Coghlan, Matthew P; Grimsby, Joseph; Dohrmann, Cord; Rhodes, Christopher J; Rondinone, Cristina M; Sharma, Arun

    2017-04-13

    Neurturin (NRTN), a member of the glial-derived neurotrophic factor (GDNF) family, was identified from an embryonic chicken pancreatic cDNA library in a screen for secreted factors. Here, we assessed the potential antidiabetic activities of NRTN relative to liraglutide, a GLP-1 receptor agonist, in Zucker diabetic fatty (ZDF) rats. Subcutaneous administration of NRTN to 8-week-old male ZDF rats prevented the development of hyperglycemia and improved metabolic parameters similar to liraglutide. NRTN treatment increased pancreatic insulin content and β-cell mass, and prevented deterioration of islet organization. However, unlike liraglutide-treated rats, NRTN-mediated improvements were not associated with reduced body weight or food intake. Acute NRTN treatment did not activate c-Fos expression in key feeding behavior and metabolic centers in ZDF rat brain or directly enhance glucose-stimulated insulin secretion from pancreatic β-cells. Treating 10-week-old ZDF rats with sustained hyperglycemia with liraglutide resulted in some alleviation of hyperglycemia, whereas NRTN was not as effective despite improving plasma lipids and fasting glucose levels. Interestingly, co-administration of NRTN and liraglutide normalized hyperglycemia and other metabolic parameters, demonstrating that combining therapies with distinct mechanism(s) can alleviate advanced diabetes. This emphasizes that therapeutic combinations can be more effective to manage diabetes in individuals with uncontrolled hyperglycemia.

  3. Elevation of circulating LOX-1 ligand levels in Zucker obese and diabetic rats.

    PubMed

    Wakabayashi, Ichiro; Shimomura, Tomoko; Nakanishi, Mamoru; Uchida, Kagehiro

    2015-01-01

    LOX-1 ligands containing apolipoprotein B (LAB) reflect ligand activity of LOX-1, which is a key molecule for initiation of atherosclerosis. The Zucker rat is a well-known model used for research on obesity and diabetes. Blood levels of LAB were compared among Zucker fatty (ZF), Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats. Log-transformed LAB was significantly higher in ZF and ZDF rats than in control ZL rats, while no significant difference was found in log-transformed LAB of ZF and ZDF rats. This study for the first time demonstrated that circulating LOX-1 ligands were elevated in obesity and diabetes model rats.

  4. The Metal Chelators, Trientine and Citrate, Inhibit the Development of Cardiac Pathology in the Zucker Diabetic Rat

    PubMed Central

    Baynes, John W.; Murray, David B.

    2009-01-01

    Purpose. The objective of this study was to determine the efficacy of dietary supplementation with the metal chelators, trientine or citric acid, in preventing the development of cardiomyopathy in the Zucker diabetic rat. Hypothesis. We hypothesized that dietary chelators would attenuate metal-catalyzed oxidative stress and damage in tissues and protect against pathological changes in ventricular structure and function in type II diabetes. Methods. Animals (10 weeks old) included lean control (LC, fa/+), untreated Zucker diabetic fatty (ZDF, fa/fa), and ZDF rats treated with either trientine (triethylenetetramine) or citrate at 20 mg/d in drinking water, starting when rats were frankly diabetic. Cardiac functional assessment was determined using a Millar pressure/volume catheter placed in the left ventricle at 32 weeks of age. Results. End diastolic volume for the ZDF animals increased by 36% indicating LV dilatation (P < .05) and was accompanied by a 30% increase in the end diastolic pressure (P ≤ .05). Both trientine and citric acid prevented the increases in EDV and EDP (P < .05). Ejection fraction and myocardial relaxation were also significantly improved with chelator treatment. Conclusion. Dietary supplementation with trientine and citric acid significantly prevented structural and functional changes in the diabetic heart, supporting the merits of mild chelators for prevention of cardiovascular disease in diabetes. PMID:19390595

  5. The metal chelators, trientine and citrate, inhibit the development of cardiac pathology in the Zucker diabetic rat.

    PubMed

    Baynes, John W; Murray, David B

    2009-01-01

    The objective of this study was to determine the efficacy of dietary supplementation with the metal chelators, trientine or citric acid, in preventing the development of cardiomyopathy in the Zucker diabetic rat. We hypothesized that dietary chelators would attenuate metal-catalyzed oxidative stress and damage in tissues and protect against pathological changes in ventricular structure and function in type II diabetes. Animals (10 weeks old) included lean control (LC, fa/+), untreated Zucker diabetic fatty (ZDF, fa/fa), and ZDF rats treated with either trientine (triethylenetetramine) or citrate at 20 mg/d in drinking water, starting when rats were frankly diabetic. Cardiac functional assessment was determined using a Millar pressure/volume catheter placed in the left ventricle at 32 weeks of age. End diastolic volume for the ZDF animals increased by 36% indicating LV dilatation (P < .05) and was accompanied by a 30% increase in the end diastolic pressure (P diabetic heart, supporting the merits of mild chelators for prevention of cardiovascular disease in diabetes.

  6. In Vivo Evaluation of Anti Diabetic, Hypolipidemic, Antioxidative Activities of Saudi Date Seed Extract on Streptozotocin Induced Diabetic Rats

    PubMed Central

    Mohieldein, Abdelmarouf

    2016-01-01

    Introduction Phoenix dactylifera (date palm) is major fruit of gulf region. In folk medicine; dates have been traditionally use. The date seed is used as hypoglycaemic, expectorant, tonic, aphrodisiac, antidiarrheic and mouth hygiene. Aim This study intended to evaluate the anti-diabetic, hypolipidaemic and antioxidative activities of date seed extract in diabetes-induced rats. Materials and Methods Total of seven groups of rats, consisting of control rats and streptozotocin induced diabetic rats treated with aqueous seed extract in concentration of 100g/L in dosage of 10ml/day/rat. To evaluate the anti-diabetic property, glucose and weight was analysed weekly and at the end of eight week all rats were sacrificed. To evaluate the hypolipidaemic and antioxidative activities, serum cholesterol, triglyceride, malondialdehyde, superoxide dismutase, 8-hydroxy-2’-deoxyguanosine were estimated. Liver enzymes and kidney function tests were performed. Moreover to verify the glycaemic effect; glycated haemoglobin and serum insulin was performed. Results Aqueous seed extract in concentration of 100 gm/L in dosage of 10ml/day/rat brings a significant reduction of blood glucose levels in diabetic rats in comparison of control rats. There were significant differences in the investigated clinical chemistry and oxidative stress parameters between control and diabetic rats with both seed extract of Ajwa and Sukkari dates. Conclusion Present study verifies the antidiabetic property, of aqueous seed extracts of two different varieties of dates namely Ajwa and Sukkari of Kingdom of Saudi on streptozotocin induced Diabetic rats. Prolong treatments with the extract restores the function of liver and kidney and balance the oxidative stress condition in diabetic treated rats. PMID:27134893

  7. Hyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist

    NASA Astrophysics Data System (ADS)

    Johnson, David G.; Ulichny Goebel, Camy; Hruby, Victor J.; Bregman, Marvin D.; Trivedi, Dev

    1982-02-01

    The glucagon analog [l-Nα-trinitrophenylhistidine, 12-homoarginine]-glucagon (THG) was examined for its ability to lower blood glucose concentrations in rats made diabetic with streptozotocin. In vitro, THG is a potent antagonist of glucagon activation of the hepatic adenylate cyclase assay system. Intravenous bolus injections of THG caused rapid decreases (20 to 35 percent) of short duration in blood glucose. Continuous infusion of low concentrations of the inhibitor led to larger sustained decreases in blood glucose (30 to 65 percent). These studies demonstrate that a glucagon receptor antagonist can substantially reduce blood glucose levels in diabetic animals without addition of exogenous insulin.

  8. Experimental Gestational Diabetes Mellitus Induces Blunted Vasoconstriction and Functional Changes in the Rat Aorta

    PubMed Central

    Tufiño, Cecilia; Villanueva-López, Cleva; Ibarra-Barajas, Maximiliano; Bracho-Valdés, Ismael; Bobadilla-Lugo, Rosa Amalia

    2014-01-01

    Diabetic conditions increase vascular reactivity to angiotensin II in several studies but there are scarce reports on cardiovascular effects of hypercaloric diet (HD) induced gestational diabetes mellitus (GDM), so the objective of this work was to determine the effects of HD induced GDM on vascular responses. Angiotensin II as well as phenylephrine induced vascular contraction was tested in isolated aorta rings with and without endothelium from rats fed for 7 weeks (4 before and 3 weeks during pregnancy) with standard (SD) or hypercaloric (HD) diet. Also, protein expression of AT1R, AT2R, COX-1, COX-2, NOS-1, and NOS-3 and plasma glucose, insulin, and angiotensin II levels were measured. GDM impaired vasoconstrictor response (P < 0.05 versus SD) in intact (e+) but not in endothelium-free (e−) vessels. Losartan reduced GDM but not SD e− vasoconstriction (P < 0.01 versus SD). AT1R, AT2R, and COX-1 and COX-2 protein expression were significantly increased in GDM vessels (P < 0.05 versus SD). Results suggest an increased participation of endothelium vasodilator mediators, probably prostaglandins, as well as of AT2 vasodilator receptors as a compensatory mechanism for vasoconstrictor changes generated by experimental GDM. Considering the short term of rat pregnancy findings can reflect early stage GDM adaptations. PMID:25610861

  9. Hypoglycemic and antioxidant effects of honey supplementation in streptozotocin-induced diabetic rats.

    PubMed

    Erejuwa, O O; Omotayo, Erejuwa O; Gurtu, Sunil; Sulaiman, Siti Amrah; Ab Wahab, Mohd Suhaimi; Sirajudeen, K N S; Salleh, Md Salzihan Md

    2010-01-01

    Oxidative stress plays a crucial role in the development of diabetic complications. The aims of this study were to investigate whether honey could reduce hyperglycemia and ameliorate oxidative stress in kidneys of streptozotocin-induced diabetic rats. Diabetes was induced by a single dose of STZ (60 mg/kg; i. p.). Diabetic rats were randomly grouped and administered distilled water (0.5 mL/day) and honey (0.2 g/kg/day, 1.2 g/kg/day and 2.4 g/kg/day) by oral gavage for four weeks. Each group consisted of six rats. Total antioxidant status (TAS), activities of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST) were significantly reduced, while superoxide dismutase (SOD) activity was up-regulated in kidneys of diabetic rats. Lipid peroxidation (TBARS) and fasting plasma glucose (FPG) were significantly elevated while body weight was reduced in diabetic rats. Honey significantly increased body weight, TAS, activities of CAT, GPx, GR, and GST in diabetic rats. It significantly restored SOD activity, and reduced FPG and TBARS levels in diabetic rats. Histopathological examinations of the kidneys revealed that mesangial matrix expansion and thickening of glomerular basement membrane were reduced in the honey-treated diabetic rats. Honey exerts a hypoglycemic effect and ameliorates oxidative stress in kidneys of streptozotocin-induced diabetic rats.

  10. Anti-diabetic Effect of Fermented Milk Containing Conjugated Linoleic Acid on Type II Diabetes Mellitus

    PubMed Central

    Yang, Hee-Sun; Lee, Sang-Cheon; Huh, Chang-Ki

    2016-01-01

    Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. CLA has been reported to be able to reduce body fat. In this study, we investigated the antidiabetic effect of fermented milk (FM) containing CLA on type II diabetes db/db mice. Mice were treated with 0.2% low FM, 0.6% high FM, or Glimepiride (GLM) for 6 wk. Our results revealed that the body weight and the levels of fasting blood glucose, serum insulin, and leptin were significantly decreased in FM fed mice compared to db/db mice. Oral glucose tolerance and insulin tolerance were significantly ameliorated in FM fed mice compared to db/db mice. Consistent with these results, the concentrations of serum total cholesterol, triglycerides, and LDL cholesterol were also significantly decreased in FM fed mice compared to db/db mice. However, the concentration of HDL cholesterol was significantly higher in FM fed mice compared to db/db mice. These results were similar to those of GLM, a commercial anti-diabetic drug. Therefore, our results suggest that FM has anti-diabetic effect as a functional food to treat type II diabetes mellitus. PMID:27194924

  11. Catechin Treatment Ameliorates Diabetes and Its Complications in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh

    2017-01-01

    Context: Diabetes mellitus causes atherosclerosis and lipid abnormalities. Hypolipidemic and antioxidative properties of catechin (CTN) have been reported in several studies. Objective: This study assesses the possible protective effects of CTN against oxidative damage in the diabetic rats. Materials and Methods: The rats were divided into the control, untreated diabetic, and 3 CTN-treated diabetic groups (20, 40, and 80 mg/kg/d, intraperitoneal). The diabetic rats were induced by streptozotocin. Catechin was injected for 4 weeks. At the end of the experimental period, glucose, lipid profile, apoprotein A-I (apo A-I), apoprotein B (apo B), malondialdehyde (MDA) levels, and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in serum. Statistical analyses were performed using the InStat 3.0 program. Results: Streptozotocin caused an elevation of glucose, MDA, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apo B with reduction in high-density lipoprotein cholesterol (HDL-C), apo A-I, SOD, CAT, and GST in the serum (P < .05). The findings showed that the significant elevation in the body weight, glucose, MDA, TG, TC, LDL-C, and apo B and reduction in HDL-C, apo A-I, SOD, CAT, and GST were ameliorated in the CTN-treated diabetic groups versus the untreated group, in a dose-dependent manner (P < .05). Conclusion: The present investigation proposes that CTN may ameliorate diabetes and its complications by modification of oxidative stress. PMID:28228702

  12. Melatonin improves glucose homeostasis in young Zucker diabetic fatty rats.

    PubMed

    Agil, Ahmad; Rosado, Isaac; Ruiz, Rosario; Figueroa, Adriana; Zen, Nourahouda; Fernández-Vázquez, Gumersindo

    2012-03-01

    The aim of this study was to investigate the effects of melatonin on glucose homeostasis in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n=30) and lean littermates (ZL) (n=30) were used. At 6wk of age, both lean and fatty animals were subdivided into three groups, each composed of ten rats: naive (N), vehicle treated (V), and melatonin treated (M) (10mg/kg/day) for 6wk. Vehicle and melatonin were added to the drinking water. ZDF rats developed DM (fasting hyperglycemia, 460±39.8mg/dL; HbA(1) c 8.3±0.5%) with both insulin resistance (HOMA-IR 9.28±0.9 versus 1.2±0.1 in ZL) and decreased β-cell function (HOMA1-%B) by 75%, compared with ZL rats. Melatonin reduced fasting hyperglycemia by 18.6% (P<0.05) and HbA(1) c by 11% (P<0.05) in ZDF rats. Also, melatonin lowered insulinemia by 15.9% (P<0.05) and HOMA-IR by 31% (P<0.01) and increased HOMA1-%B by 14.4% (P<0.05). In addition, melatonin decreased hyperleptinemia by 34% (P<0.001) and raised hypoadiponectinemia by 40% (P<0.001) in ZDF rats. Moreover, melatonin reduced serum free fatty acid levels by 13.5% (P<0.05). These data demonstrate that oral melatonin administration ameliorates glucose homeostasis in young ZDF rats by improving both insulin action and β-cell function. These observations have implications on melatonin's possible use as a new pharmacologic therapy for improving glucose homeostasis and of obesity-related T2DM, in young subjects.

  13. Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats

    SciTech Connect

    Winocour, P.D.; Colwell, J.A.

    1985-05-01

    Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, the authors used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. The authors conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis.

  14. Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats

    PubMed Central

    2011-01-01

    Background Diabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD). Aim of the study The objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats. Methods Diabetes was induced in the animals through intravenous administration of alloxan. The rats were divided into four groups: Diabetic Control (DC) - diabetic rats fed with a control diet and no physical exercise; Diabetic Spirulina (DS) - diabetic rats fed with a diet that included spirulina; Diabetic Spirulina and Exercise (DSE) - diabetic rats fed with a diet that included Spirulina and that exercised; and Diabetic Exercise (DE) - diabetic rats fed with a control diet and that exercised. Results The groups DS, DSE, and DE presented lower plasma concentrations of LDL cholesterol than DC, as well as lower levels of total liver lipids in groups DS, DSE, and DE in comparison to DC. Conclusion Thus, spirulina appears to be effective in reducing total circulating levels of LDL-cholesterol and hepatic lipids, alone or in conjunction with physical exercise in diabetic rats. PMID:21569626

  15. Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats.

    PubMed

    Moura, Leandro P; Puga, Guilherme M; Beck, Wladimir R; Teixeira, Inaian P; Ghezzi, Ana Carolina; Silva, Gláucio A; Mello, Maria Alice R

    2011-05-15

    Diabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD). The objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats. Diabetes was induced in the animals through intravenous administration of alloxan. The rats were divided into four groups: Diabetic Control (DC) - diabetic rats fed with a control diet and no physical exercise; Diabetic Spirulina (DS) - diabetic rats fed with a diet that included spirulina; Diabetic Spirulina and Exercise (DSE) - diabetic rats fed with a diet that included Spirulina and that exercised; and Diabetic Exercise (DE) - diabetic rats fed with a control diet and that exercised. The groups DS, DSE, and DE presented lower plasma concentrations of LDL cholesterol than DC, as well as lower levels of total liver lipids in groups DS, DSE, and DE in comparison to DC. Thus, spirulina appears to be effective in reducing total circulating levels of LDL-cholesterol and hepatic lipids, alone or in conjunction with physical exercise in diabetic rats.

  16. Renal effects of antihypertensive therapy in uninephrectomized diabetic rats.

    PubMed

    Gallego, B; Flores, O; López-Novoa, J M; Pérez-Barriocanal, F

    1997-01-01

    Diabetic nephropathy is a major cause of chronic renal failure. The evidence available indicates that renal hemodynamics are altered in clinical and experimental diabetes mellitus. In these circumstances, an increased glomerular filtration rate (GFR) is associated with albuminuria and eventually with glomerulosclerosis. We studied the renal and hemodynamic effects of long-term treatment (5 months) using an angiotensin-converting enzyme inhibitor (trandolapril, 0.7 mg/g b.w. per day) and a calcium antagonist (verapamil, 20 mg/g b.w. per day), and the combination of the two (veratran) at the same dose, on streptozotocin-diabetic uninephrectomized rats. A moderate degree of hyperglycemia (2-4 g/l) was maintained with daily insulin. Mean arterial pressure (MAP) was measured monthly using the tail-cuff method. Determinations were made of urinary protein excretion, creatinine clearance, urinary electrolyte excretion and, at the end of treatment, renal and cardiac hypertrophy. MAP was similar in control and untreated diabetic rats. Trandolapril and veratran reduced MAP whereas verapamil alone had no effect on these animals. All groups showed a slight proteinuria that increased with verapamil treatment. The GFR of diabetic animals was higher than in the control group (mainly the first 2 months), except for veratran group, in which it was similar to the control value. Urinary electrolyte excretion increased in all diabetic groups with no significant differences among them. Veratran induced a protective effect against cardiac hypertrophy. None of the treatments affected renal hypertrophy. It is concluded that in a murine model of diabetes without hypertension or proteinuria, a combination of verapamil and trandolapril prevents hyperfiltration whereas verapamil alone increases proteinuria.

  17. Anti-depressant effect of hesperidin in diabetic rats.

    PubMed

    El-Marasy, Salma A; Abdallah, Heba M I; El-Shenawy, Siham M; El-Khatib, Aiman S; El-Shabrawy, Osama A; Kenawy, Sanaa A

    2014-11-01

    This study aimed to investigate the anti-depressant effect of hesperidin (Hsp) in streptozotocin (STZ)-induced diabetic rats. Additionally, the effect of Hsp on hyperglycaemia, oxidative stress, inflammation, brain-derived neurotrophic factor (BDNF), and brain monoamines in diabetic rats was also assessed. The Wistar rats in the experimental groups were rendered hyperglycaemic with a single dose of STZ (52.5 mg·(kg body mass)(-1), by intraperitoneal injection). The normal group received the vehicle only. Hyperglycaemic rats were treated with Hsp (25.0, 50.0, or 100.0 mg·(kg body mass)(-1)·day(-1), per oral) and fluoxetine (Flu) (5.0 mg·(kg body mass)(-1)·day(-1), per oral) 48 h after the STZ injection, for 21 consecutive days. The normal and STZ control groups received the vehicle (distilled water). Behavioral and biochemical parameters were then assessed. When Hsp was administered to the STZ-treated rats, this reversed the STZ-induced increase in immobility duration in the forced swimming test (FST) and attenuated hyperglycaemia, decreased malondialdehyde (MDA), increased reduced glutathione (GSH) decreased interleukin-6 (IL-6), and increased BDNF levels in the brain. Treatment with Hsp attenuated STZ-induced neurochemical alterations, as indicated by increased levels of monoamines in the brain, namely, norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine; 5-HT). All of these effects of Hsp were similar to those observed with the established anti-depressant Flu. This study shows that Hsp exerted anti-depressant effect in diabetic rats, which may have been partly mediated by its amelioration of hyperglycaemia as well as its anti-oxidant and anti-inflammatory activities, the enhancement of neurogenesis, and changes in the levels of monoamines in the brain.

  18. Anti-diabetic activity of alcoholic extract of Celosia argentea Linn. seeds in rats.

    PubMed

    Vetrichelvan, Thangarasu; Jegadeesan, Maniappan; Devi, Bangaru Adigalar Uma

    2002-04-01

    Celosia argentea Linn. commonly known as "Cocks Comb" and its seeds are widely used in Indian folk medicine for the treatment of diabetes mellitus. This study was undertaken to evaluate the effect of an alcoholic extract of Celosia argentea seeds (ACAS) on blood glucose and body weight in alloxan-induced diabetic rats. ACAS was found to reduce the increase of blood glucose in alloxan-induced diabetic rats (27.8% at 250 mg/kg and 38.8% at 500 mg/kg body weight). Chronic administration of ACAS significantly (p<0.01) reduced the blood glucose in alloxan-induced diabetic rats for two weeks. Also the extract prevented a decrease in body weight in alloxan-induced diabetic rats. These results suggest that the ACAS possesses anti-diabetic activity in alloxan-induced diabetic rats.

  19. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

    PubMed Central

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle. PMID:27190533

  20. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle.

    PubMed

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL(-1) for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL(-1). The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle.

  1. Accelerated degradation of collagen membranes in diabetic rats is associated with increased infiltration of macrophages and blood vessels.

    PubMed

    Moses, Ofer; Eliezer, Meizi; Nemcovsky, Carlos; Tal, Haim; Weinreb, Miron

    2016-09-01

    Increased collagenolytic activity in diabetes may compromise collagen membrane (CM) survival. Tetracycline (TTC) possesses anti-collagenolytic properties and delays CM degradation. This study evaluated macrophage and capillary infiltration within CMs in diabetic rats. Diabetes was induced in 20 Wistar rats by streptozotocin and 20 served as controls. Biotin-labeled CM discs were immersed in either TTC (50 mg/ml) or PBS. In each animal, 2 discs (TTC and control) were implanted under the parietal periosteum and rats were sacrificed at 2 or 4 weeks post-implantation. The area and thickness of the residual disc collagen were measured following staining with streptavidin, and the number of macrophages and blood vessels within the membranes was determined using specific antibodies (to CD68 and transglutaminase II, respectively). Diabetes significantly reduced the area and thickness of the CMs, while TTC increased CM thickness significantly in both groups of rats at 2 and 4 weeks. Diabetes increased the number of macrophages (∼eightfold at 2 weeks and ∼fourfold at 4 weeks), but TTC had no significant effect. Finally, diabetes increased the number of blood vessels within the discs (∼threefold at 2 weeks and ∼twofold at 4 weeks), while TTC had no effect. Diabetes increases degradation of native CMs and the number of blood vessels and macrophages within them. TTC immersion delays CM degradation without an apparent effect on macrophage and blood vessel penetration. Enhanced CM degradation in diabetic conditions which impair guided regenerative procedure outcome is apparently related to increased blood vessel formation and macrophage infiltration.

  2. Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: a morphological and biochemical study.

    PubMed

    Bolkent, S; Yanardag, R; Ozsoy-Sacan, O; Karabulut-Bulan, O

    2004-12-01

    Parsley is used by diabetics in Turkey to reduce blood glucose. The present study aims to investigate both the morphological and biochemical effects of parsley on liver tissue. Rat hepatocytes were examined by light and electron microscopy. Degenerative changes were observed in the hepatocytes of diabetic rats. These degenerative changes were significantly reduced or absent in the hepatocytes of diabetic rats treated with parsley. Blood glucose levels, alanine transaminase and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic rats treated with parsley demonstrated significantly lower levels of blood glucose, alanine transaminase and alkaline phosphatase. The present study suggests that parsley demonstrates a significant hepatoprotective effect in diabetic rats. 2004 John Wiley & Sons, Ltd.

  3. Tissue-specific up-regulation of arginase I and II induced by p38 MAPK mediates endothelial dysfunction in type 1 diabetes mellitus

    PubMed Central

    Pernow, J; Kiss, A; Tratsiakovich, Y; Climent, B

    2015-01-01

    Background and Purpose Emerging evidence suggests a selective up-regulation of arginase I in diabetes causing coronary artery disease; however, the mechanisms behind this up-regulation are still unknown. Activated p38 MAPK has been reported to increase arginase II in various cardiovascular diseases. We therefore tested the role of p38 MAPK in the regulation of arginase I and II expression and its effect on endothelial dysfunction in diabetes mellitus. Experimental Approach Endothelial function was determined in septal coronary (SCA), left anterior descending coronary (LAD) and mesenteric (MA) arteries from healthy and streptozotocin-induced diabetic Wistar rats by wire myographs. Arginase activity and protein levels of arginase I, II, phospho-p38 MAPK and phospho-endothelial NOS (eNOS) (Ser1177) were determined in these arteries from diabetic and healthy rats treated with a p38 MAPK inhibitor in vivo. Key Results Diabetic SCA and MA displayed impaired endothelium-dependent relaxation, which was prevented by arginase and p38 MAPK inhibition while LAD relaxation was not affected. Arginase I, phospho-p38 MAPK and eNOS protein expression was increased in diabetic coronary arteries. In diabetic MA, however, increased expression of arginase II and phospho-p38 MAPK, increased arginase activity and decreased expression of eNOS were observed. All these effects were reversed by p38 MAPK inhibition. Conclusions and Implications Diabetes-induced activation of p38 MAPK causes endothelial dysfunction via selective up-regulation of arginase I expression in coronary arteries and arginase II expression in MA. Therefore, regional differences appear to exist in the arginase isoforms contributing to endothelial dysfunction in type 1 diabetes mellitus. PMID:26140333

  4. Efficiency of noopept in streptozotocin-induced diabetes in rats.

    PubMed

    Ostrovskaya, R U; Ozerova, I V; Gudascheva, T A; Kapitsa, I G; Ivanova, E A; Voronina, T A; Seredenin, S B

    2013-01-01

    We studied the effects of new nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) in various dosage regimens on the dynamics of glycemia, body weight, and pain sensitivity in rats receiving diabetogenic toxin streptozotocin. In experimental diabetic rats, Noopept alleviated glycemia and weight loss and normalized enhanced pain sensitivity. The normalizing effect of Noopept was most pronounced when it was administered as a preventive agent prior to injection of the toxin. Both preventive and therapeutic administration of Noopept (delayed injections included) significantly weakened the examined metabolic effects of diabetogenic toxin. Possible mechanisms of the antidiabetic action of Noopept are analyzed.

  5. Mitochondrial dysfunction driven by the LRRK2-mediated pathway is associated with loss of Purkinje cells and motor coordination deficits in diabetic rat model

    PubMed Central

    Yang, S; Xia, C; Li, S; Du, L; Zhang, L; Hu, Y

    2014-01-01

    Diabetic neuropathy develops on a background of hyperglycemia and an entangled metabolic imbalance. There is increasing evidence of central nervous system involvement in diabetic neuropathy and no satisfactory treatment except maintenance of good glycemic control, thereby highlighting the importance of identifying novel therapeutic targets. Purkinje cells are a class of metabolically specialized active neurons, and degeneration of Purkinje cells is a common feature of inherited ataxias in humans and mice. However, whether Purkinje cells are implicated in diabetic neuropathy development under metabolic stress remains poorly defined. Here, we revealed a novel leucine-rich repeat kinase 2 (LRRK2)-mediated pathway in Purkinje cells that is involved in the pathogenesis of diabetic neuropathy from a 24-week long study of streptozotocin (STZ)-diabetic rats. We found that hyperglycemia, cerebellum proinflammatory cytokines, and chemokines increased markedly in 24-week STZ-diabetic rats. Furthermore, we demonstrated that degeneration of Purkinje cells is characterized by progressive swellings of axon terminals, no autophagosome formation, the reduction of LC3II/LC3I and Lamp2, and accumulation of p62 puncta in 24-week STZ-diabetic rats. Importantly, a higher expression level of LRRK2-mediated hyperphosphorylation of tau along with increased mitochondrial dynamin-like protein (mito-DLP1) was demonstrated in 24-week STZ-diabetic rats. This effect of LRRK2 overexpression induced mitochondrial fragmentation, and reduced mitochondrial protein degradation rates were confirmed in vitro. As a consequence, 24-week STZ-diabetic rats showed mitochondrial dysfunction in cerebellar Purkinje neurons and coordinated motor deficits evaluated by rotarod test. Our findings are to our knowledge the first to suggest that the LRRK2-mediated pathway induces mitochondrial dysfunction and loss of cerebellar Purkinje neurons and, subsequently, may be associated with motor coordination deficits in

  6. Increased cutaneous NGF and CGRP-labelled trkA-positive intra-epidermal nerve fibres in rat diabetic skin.

    PubMed

    Evans, Laura; Andrew, David; Robinson, Peter; Boissonade, Fiona; Loescher, Alison

    2012-01-06

    In this study we have determined the amount of Nerve Growth Factor (NGF) and the innervation density of the glabrous hindpaw skin of diabetic rats (n=4) and controls (n=3). The proportion of intra-epidermal nerve fibres (IENF) expressing the high affinity NGF receptor (trkA) and calcitonin gene-related peptide (CGRP) were also determined. Four weeks after induction of diabetes by intraperitoneal streptozotocin injection skin was analyzed for: (i) NGF content using ELISA and (ii) the innervation density of peptidergic afferents that also expressed trkA using immunocytochemistry. NGF levels were approximately three-fold higher in diabetic skin compared to controls (diabetic: 134.7±24.0 (SD) pgml(-1), control: 42.7±21.5pgml(-1), p=0.002). As expected there was a significant reduction in IENF density in diabetic skin (2.7±1.3 fibresmm(-1)) compared to controls (6.9±1.5 fibresmm(-1); p=0.01). In diabetic rats there was no significant difference in the proportion of trkA-labelled IENF (diabetic 74±21%; control 83±15%, p=0.6), but significantly more trkA-positive IENF were also labelled by CGRP antibodies in diabetic skin compared to controls (diabetic 89±22%; control 38±2%, p=0.03). These data suggest that in diabetes the upregulation of cutaneous NGF may 'over-troph' the surviving axons, increasing CGRP labelling, which may be important in the aetiology of painful diabetic neuropathy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Risk factors for Type II diabetes and diabetic retinopathy in a mexican-american population: Proyecto VER.

    PubMed

    West, Sheila K; Munoz, Beatriz; Klein, Ronald; Broman, Aimee T; Sanchez, Rosario; Rodriguez, Jorge; Snyder, Robert

    2002-09-01

    Risk factors for type II diabetes and diabetic retinopathy were determined in a population-based study of Mexican-Americans. Proyecto VER (Vision, Evaluation, and Research) is a cross-sectional study in a random sample of the self-described Hispanic populations in Tucson and Nogales, Arizona, age 40 and older. Of 6,659 eligible subjects, 4,774 (72%) participated in the home questionnaire and clinic visit. Diabetes was defined as self-report of a physician diagnosis or hemoglobin A(1c) value of > or = 7.0%. Only type II diabetes was included. Diabetic retinopathy was assessed on stereo fundus photographs of all persons with diabetes. Questions were asked about demographic, personal, socioeconomic, and diabetes related variables. 1023 (21.4%) of the sample had type II diabetes, and 68% were in the low-income group (annual income less than $20,000). Diabetes was associated with Native-American ancestry, higher acculturation, low income, less education, and increasing body mass index after age and gender adjustment. Persons with previously undiscovered diabetes were more likely to have no regular source of care, no insurance, and currently smoke compared with persons with known diabetes. Only low income was related to proliferative retinopathy, once adjusted for other factors (odds ratio [OR] = 3.93, 95%, confidence limitations [CL] = 1.31-11.80). Several socioeconomic and other factors were associated with diabetes, but few were related to diabetic retinopathy. Persons in the low-income group appeared to be at greater risk of diabetes and the ocular complications of diabetes compared with those with more income. Further longitudinal studies in this population are needed to confirm the associations.

  8. Intestinal transport of sugars and amino acids in diabetic rats

    PubMed Central

    Olsen, Ward A.; Rosenberg, Irwin H.

    1970-01-01

    The specificity and mechanism of altered intestinal transport of diabetic rats was studied with an everted ring technique. Increased intracellular accumulation of amino acids, as well as galactose and 3-O-methylglucose, was demonstrated in diabetes. The greater accumulation by diabetic intestine could not be attributed to a direct effect of the agent used to induce diabetes or to an alteration in food consumption. Although the changes were related to the severity of diabetes and could be reversed with treatment with insulin, they could not be modified by addition of insulin in vitro. The changes could not be induced in control intestine either with hyperglycemia from glucose infusion or preincubation with glucose in vitro. Although the higher concentration gradients of amino acids, galactose, and 3-O-methylglucose could result from increased energy utilization by diabetic intestine, an alteration of cell membrane function, as well, is suggested by the demonstration with kinetic studies of increased influx with an increase in Vmax. PMID:5409812

  9. Proteoglycans in bones of streptozotocin-induced diabetic rats.

    PubMed

    Perez, C; Suarez, C; Kofoed, J

    1990-01-01

    Insulin seems to regulate the biosynthesis of proteoglycans in some tissues such as growth plate and glomeruli. The present investigation was undertaken to assess the ex vivo influence of insulin on proteoglycan metabolism in bones. Mandible and femur bones were used. Xiphoid cartilage was used as a control tissue of high glycosaminoglycan content. Diabetes was induced by 0.12 mg/g b.w. streptozotocin in male Sprague-Dawley rats, a number of which was treated with insulin (1 I.U./100 g b.w.) for 6 days. As compared with control animals, diabetic rats exhibited a decreased [35S]sulfate uptake as well as a shift to the right in Sephacryl S-500 chromatography. In addition, they showed lower density of proteoglycans in sucrose gradient and shorter glycosaminoglycan side chains in Sephadex G-200 chromatography. These changes were partly reversed by insulin.

  10. A phytooxysterol, 28-homobrassinolide modulates rat testicular steroidogenesis in normal and diabetic rats.

    PubMed

    Premalatha, R; Jubendradass, Rajamanickam; Rani, S Judith Amala; Srikumar, K; Mathur, Premendu Prakash

    2013-05-01

    Steroidogenesis in testicular cells depends upon the availability of cholesterol within testicular mitochondria besides the activities of 3β-hydroxysteroid dehydrogenase (3β-HSD, 17β-hydroxysteroid dehydrogenase [17b-HSD]), and the tissue levels of steroidogenic acute regulatory protein (StAR), androgen-binding protein (ABP), and testosterone (T). Cellular cholesterol biosynthesis is regulated by endogenous oxycholesterols acting through nuclear hormone receptors. Plant oxysterols, such as 28-homobrassinolide (28-HB), available to human through diet, was shown to exhibit antihyperglycemic effect in diabetic male rat. Its role in rat testicular steroidogenesis and lipid peroxidation (LPO) was therefore assessed using normal and streptozotocin-induced diabetic male rats. Administration of 28-HB (333 µg/kg body weight) by oral gavage for 15 consecutive days to experimental rats diminished LPO, increased antioxidant enzyme, 3β-HSD and 17β-HSD activities, and elevated StAR and ABP expression and T level in rat testis. We report that 28-HB induced steroidogenesis in normal and diabetic rat testis.

  11. Diabetes alters inflammation, angiogenesis, and fibrogenesis in intraperitoneal implants in rats.

    PubMed

    Oviedo-Socarrás, Teresa; Vasconcelos, Anilton C; Barbosa, Irma X; Pereira, Nubia B; Campos, Paula P; Andrade, Silvia P

    2014-05-01

    The increased prevalence of diabetes worldwide is associated with increasing numbers of diabetic individuals receiving synthetic matrices and biomedical implants to repair and/or replace biological tissues. This therapeutic procedure invariably leads to adverse tissue healing (foreign body reaction), thus impairing the biomedical device function of subcutaneous implants. However, the influence of diabetes on abnormal tissue healing in intraperitoneal implants is unclear. We investigated key components of foreign body reactions in diabetic rats. Polyether-polyurethane sponge discs were placed intraperitoneally in rats previously injected with streptozotocin for induction of diabetes and in non-diabetic rats. Implants removed 10 days after implantation were assessed by determining the components of the fibrovascular tissue (angiogenesis, inflammation, and fibrogenesis). In implants from diabetic rats, fibrous capsule thickness and fibrovascular tissue infiltration (hematoxylin & eosin and picrosirius staining) were reduced in comparison with implants from non-diabetic rats. Hemoglobin (Hb) content (vascular index) and VEGF levels (pro-angiogenic cytokine) were increased after diabetes. However, the number of vessels (H&E and CD31-immunostaining) in the fibrovascular tissue from diabetic rats was decreased when compared with vessel numbers in implants from non-diabetic animals. Overall, all inflammatory parameters (macrophage accumulation-NAG activity; TNF-α and MCP-1 levels) increased in intraperitoneal implants after diabetes induction. The pro-fibrogenic cytokine (TGFβ-1) increased after diabetes, but collagen deposition remained unaltered in the implants from diabetic rats. These important diabetes-related changes (increased levels of pro-inflammatory and angiogenic and fibrogenic cytokines) in peritoneal implant healing provide an insight into the mechanisms of the foreign body response in the diabetic environment in rats. Copyright © 2014 Elsevier Inc. All

  12. Histopathological changes in liver, kidney and muscles of pesticides exposed malnourished and diabetic rats.

    PubMed

    Benjamin, Nidhi; Kushwah, Ameeta; Sharma, R K; Katiyar, A K

    2006-03-01

    Histopathological changes were observed in liver, kidney and muscles of normal, protein-malnourished, diabetic as well as both protein-malnourished and diabetic albino rats when exposed to a mixture of monocrotophos, hexachlorocyclohexane and endosulfan at varying intervals. The examination revealed hepatotoxic, nephrotoxic and muscular necrotic effects in pesticides exposed rats. Toxicity was aggravated in protein-malnourished and diabetic animals and more so, if the animals were both diabetic and protein-malnourished.

  13. Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats.

    PubMed

    Akhtar, Muhammad Tayyab; Bin Mohd Sarib, Mohamad Syakir; Ismail, Intan Safinar; Abas, Faridah; Ismail, Amin; Lajis, Nordin Hj; Shaari, Khozirah

    2016-08-09

    Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese-diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

  14. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats.

    PubMed

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨ m ), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

  15. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats

    PubMed Central

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R.; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨm), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress. PMID:26180820

  16. Effect of L-carnitine treatment on lipid metabolism and cardiac performance in chronically diabetic rats.

    PubMed

    Rodrigues, B; Xiang, H; McNeill, J H

    1988-10-01

    The beneficial effects of L-carnitine administration were studied in vivo in isolated perfused working hearts from control and diabetic rats. Control and streptozocin-induced diabetic (STZ-D) rats were treated daily for 6 wk with high-dose L-carnitine (3 g.kg-1.day-1 i.p.). STZ-D results in loss of body weight and hypoinsulinemia. These effects were not altered by L-carnitine treatment. Myocardial free-carnitine levels were decreased in the untreated diabetic rats. L-Carnitine treatment of the diabetic rats increased myocardial free-carnitine levels, which were comparable with those of control rats. Six weeks after STZ administration, hearts from untreated diabetic animals exhibited depressed left ventricular developed pressure, cardiac contractility, and ventricular relaxation rates compared with control animals. However, this depression was not seen in the L-carnitine-treated diabetic animals. L-Carnitine treatment of diabetic rats significantly reduced plasma glucose and lipid levels but had no effect on control rats. Furthermore, thyroid hormone levels were higher in the L-carnitine-treated diabetic rats than in the untreated diabetic group. The data suggest that high-dose L-carnitine treatment may reduce the severity of diabetes and result in improved cardiac performance.

  17. Protective effect of potato peel powder in ameliorating oxidative stress in streptozotocin diabetic rats.

    PubMed

    Singh, Nandita; Kamath, Vasudeva; Rajini, P S

    2005-06-01

    The potential of dietary potato peel (PP) powder in ameliorating oxidative stress (OS) and hyperglycemia was investigated in streptozotocin (STZ)-induced diabetic rats. In a 4-week feeding trial, incorporation of potato peel powder (5 and 10%) in the diet of diabetic rats was found to significantly reduce the plasma glucose level and also reduce drastically the polyuria of STZ diabetic rats. The total food intake was significantly reduced in the diabetic rats fed 10% PP powder compared to the control diabetic rats. However, the body weight gain over 28 days was nearly four times greater in PP powder supplemented diabetic rats (both at 5 and 10%) compared to the control diabetic rats. PP powder in the diet also decreased the elevated activities of serum transaminases (ALT and AST) and nearly normalized the hepatic MDA and GSH levels as well as the activities of specific antioxidant enzymes in liver of diabetic rats. The result of these studies clearly establishes the modulatory propensity of PP against diabetes induced alterations. Considering that potato peels are discarded as waste and not effectively utilized, these results suggest the possibility that PP waste could be effectively used as an ingredient in health and functional food to ameliorate certain disease states such as diabetes.

  18. Attenuation of erythrocyte membrane oxidative stress by Sesbania grandiflora in streptozotocin-induced diabetic rats.

    PubMed

    Sureka, Chandrabose; Ramesh, Thiyagarajan; Begum, Vavamohaideen Hazeena

    2015-08-01

    The aim of the present study was to investigate the protective effects of Sesbania grandiflora flower (SGF) extract on erythrocyte membrane in Streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 190-220 g, were made diabetic by an intraperitonial administration of STZ (45 mg/kg). Normal and diabetic rats were treated with SGF, and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In this study plasma insulin and haemoglobin levels were decreased and blood glucose, glycosylated haemoglobin, protein oxidation, lipid peroxidation markers, and osmotic fragility levels were increased in diabetic rats. Moreover, erythrocytes antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxide, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities and non-enzymatic antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), and oxidized glutathione (GSSG) levels were altered. Similarly, the activities of total ATPases, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase were also decreased in the erythrocytes of diabetic rats. Administration of SGF to STZ-induced diabetic rats reduced blood glucose and glycosylated haemoglobin levels with increased levels of insulin and haemoglobin. Moreover, SGF reversed the protein and lipid peroxidation markers, osmotic fragility, membrane-bound ATPases activities, and antioxidant status in STZ-induced diabetic rats. These results suggest that SGF could provide a protective effect on diabetes by decreasing oxidative stress-associated diabetic complications.

  19. Decreased Neuronal Bursting and Phase Synchrony in the Hippocampus of Streptozotocin Diabetic Rats

    PubMed Central

    Xie, Kangning; Li, Guoliang

    2014-01-01

    Diabetic encephalopathy is one of the complications of diabetes. Cognitive dysfunction is the main consequence. Previous findings from neuroanatomical and in vitro electrophysiological studies showed that the structure and function of the hippocampus is impaired in diabetes, which may underlie the cognitive dysfunction induced by diabetes. However the study of electrophysiological abnormality of hippocampal neurons in intact networks is sparse. In the current study, we recorded the spontaneous firing of neurons in hippocampal CA1 area in anesthetized streptozotozin (STZ)-diabetic and age-matched control rats. Profound reduction in burst activity was found in diabetic rats. Compared to control rats, the intra-burst inter-spike intervals were prolonged significantly in diabetic rats, while the burst ratio and the mean number of spikes within a burst decreased significantly. Treatment with APP 17-mer peptide retarded the effects of diabetes on these parameters. In addition, the average PLV of diabetic rats was lower than that of control rats. These findings provide in vivo electrophysiological evidence for the impairment of hippocampal function in STZ-diabetic rats, and may have some implications in the mechanisms associated with cognitive deficits in diabetes. PMID:25093193

  20. Balneotherapy and platelet glutathione metabolism in type II diabetic patients

    NASA Astrophysics Data System (ADS)

    Ohtsuka, Yoshinori; Yabunaka, Noriyuki; Watanabe, Ichiro; Noro, Hiroshi; Agishi, Yuko

    1996-09-01

    Effects of balneotherapy on platelet glutathione metabolism were investigated in 12 type II (non-insulin-dependent) diabetic patients. Levels of the reduced form of glutathione (GSH) on admission were well correlated with those of fasting plasma glucose (FPG; r=0.692, P<0.02). After 4 weeks of balneotherapy, the mean level of GSH showed no changes; however, in well-controlled patients (FPG <150 mg/dl), the level increased ( P<0.01) and in poorly controlled patients (FPG >150 mg/dl), the value decreased ( P<0.05). There was a negative correlation between glutathione peroxidase (GPX) activities and the levels of FPG ( r=-0.430, P<0.05). After balneotherapy, the activity increased in 5 patients, decreased in 3 patients and showed no changes (alteration within ±3%) in all the other patients. From these findings in diabetic patients we concluded: (1) platelet GSH synthesis appeared to be induced in response to oxidative stress; (2) lowered GPX activities indicated that the antioxidative defense system was impaired; and (3) platelet glutathione metabolism was partially improved by 4 weeks balneotherapy, an effect thought to be dependent on the control status of plasma glucose levels. It is suggested that balneotherapy is beneficial for patients whose platelet antioxidative defense system is damaged, such as those with diabetes mellitus and coronary heart disease.

  1. Health perceptions among urban American Indians with type II diabetes.

    PubMed

    Patel, Sachin; Davila, Javier; Patel, Sonam; Norman, Dennis

    2014-01-01

    Since the 1940s, American Indians (AIs) have increasingly urbanized, moving off of reservations in large part due to federal policies of tribal termination and relocation. Though previous AI research has largely focused on reservation-associated challenges, many of these same challenges persist among urban AI populations. One mutual concern is the growing prevalence and incidence of type II diabetes mellitus (T2DM). While behavioral, genetic, and socioeconomic determinants of T2DM have been explored, much less is known about the influence of cultural and psychosocial factors. Recent studies suggest that the way AIs perceive diabetes may affect their health trajectory and explain their poor prognosis. Through the use of the Illness Perception Questionnaire, we explored this hypothesis in a pilot study of urban AI with T2DM living in Los Angeles County. We found that the majority of participants have a neutral perception about their diabetes: They view their condition to be long lasting yet treatable and indicate reasonable understanding of its symptoms and progression. We also identified "personal control," the level of perceived control one has over his or her disease, as a strong correlate of overall illness perception and, thus, a potentially useful psychological metric.

  2. The effect of endotoxin on heart rate dynamics in diabetic rats.

    PubMed

    Meamar, Morvarid; Dehpour, Tara; Mazloom, Roham; Sharifi, Fatemeh; Raoufy, Mohammad R; Dehpour, Ahmad R; Mani, Ali R

    2015-05-01

    The effect of endotoxin on heart rate variability (HRV) was assessed in diabetic and controls rats using a telemetric system. Endotoxin induced a reduction in sample entropy of cardiac rhythm in control animals. However, this effect was significantly blunted in streptozotocin-induced diabetic rats. Since uncoupling of cardiac pacemaker from cholinergic control is linked to reduced HRV in endotoxemia, chronotropic responsiveness to cholinergic stimulation was assessed in isolated atria. Endotoxemia was associated with impaired responsiveness to carbacholine in control rats. However, endotoxemia did not impair cholinergic responsiveness in diabetic atria. These findings corroborates with development of endotoxin tolerance in diabetic rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Chromium and manganese interactions in streptozocin-diabetic rats

    SciTech Connect

    Davis, M.L.; Jarrett, C.R.; Adeleye, B.O.; Stoecker, B.J. )

    1991-03-15

    Weanling male rats were fed casein-based diets low in chromium and manganese ({minus}Cr-MN) or supplemented with 1 ppm chromium as chromium chloride (+Cr) and/or 55 ppm manganese as manganous carbonate in a factorial design. After 7 weeks on the experimental diets, half of the rats in each group were injected on 2 consecutive days with 55 mg/kg streptozocin (STZ) in citrate buffer pH 4. Four weeks after injection, serum glucose in the diabetic group supplement with both Cr and Mn was not different from non-diabetic animals; however, diabetic animals in {minus}Cr groups or in the +Cr-Mn group had significantly elevated serum glucose. Serum insulin was reduced by STZ. A significant interaction between Mn and diabetes affected serum cortisol concentrations. More new tissue was formed on a polyvinyl sponge inserted under the skin in +Mn animals. In this study, the STZ animals were more sensitive than the control animals to dietary Cr and Mn concentrations.

  4. Reversal of Diabetes Through Gene Therapy of Diabetic Rats by Hepatic Insulin Expression via Lentiviral Transduction

    PubMed Central

    Elsner, Matthias; Terbish, Taivankhuu; Jörns, Anne; Naujok, Ortwin; Wedekind, Dirk; Hedrich, Hans-Jürgen; Lenzen, Sigurd

    2012-01-01

    Due to shortage of donor tissue a cure for type 1 diabetes by pancreas organ or islet transplantation is an option only for very few patients. Gene therapy is an alternative approach to cure the disease. Insulin generation in non-endocrine cells through genetic engineering is a promising therapeutic concept to achieve insulin independence in patients with diabetes. In the present study furin-cleavable human insulin was expressed in the liver of autoimmune-diabetic IDDM rats (LEW.1AR1/Ztm-iddm) and streptozotocin-diabetic rats after portal vein injection of INS-lentivirus. Within 5–7 days after the virus injection of 7 × 109 INS-lentiviral particles the blood glucose concentrations were normalized in the treated animals. This glucose lowering effect remained stable for the 1 year observation period. Human C-peptide as a marker for hepatic release of human insulin was in the range of 50–100 pmol/ml serum. Immunofluorescence staining of liver tissue was positive for insulin showing no signs of transdifferentiation into pancreatic β-cells. This study shows that the diabetic state can be efficiently reversed by insulin release from non-endocrine cells through a somatic gene therapy approach. PMID:22354377

  5. Reversal of diabetes through gene therapy of diabetic rats by hepatic insulin expression via lentiviral transduction.

    PubMed

    Elsner, Matthias; Terbish, Taivankhuu; Jörns, Anne; Naujok, Ortwin; Wedekind, Dirk; Hedrich, Hans-Jürgen; Lenzen, Sigurd

    2012-05-01

    Due to shortage of donor tissue a cure for type 1 diabetes by pancreas organ or islet transplantation is an option only for very few patients. Gene therapy is an alternative approach to cure the disease. Insulin generation in non-endocrine cells through genetic engineering is a promising therapeutic concept to achieve insulin independence in patients with diabetes. In the present study furin-cleavable human insulin was expressed in the liver of autoimmune-diabetic IDDM rats (LEW.1AR1/Ztm-iddm) and streptozotocin-diabetic rats after portal vein injection of INS-lentivirus. Within 5-7 days after the virus injection of 7 × 10(9) INS-lentiviral particles the blood glucose concentrations were normalized in the treated animals. This glucose lowering effect remained stable for the 1 year observation period. Human C-peptide as a marker for hepatic release of human insulin was in the range of 50-100 pmol/ml serum. Immunofluorescence staining of liver tissue was positive for insulin showing no signs of transdifferentiation into pancreatic β-cells. This study shows that the diabetic state can be efficiently reversed by insulin release from non-endocrine cells through a somatic gene therapy approach.

  6. Dietary soy isoflavones increase insulin secretion and prevent the development of diabetic cataracts in streptozotocin-induced diabetic rats.

    PubMed

    Lu, Mei-Ping; Wang, Rui; Song, Xiuyuan; Chibbar, Rajni; Wang, Xiaoxia; Wu, Lingyun; Meng, Qing H

    2008-07-01

    Soy isoflavone-containing diets have been reported to be beneficial in diabetes. This present study investigated the hypoglycemic effects of isoflavones in streptozotocin (STZ)-induced diabetes. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 100 mg/kg STZ. Diabetic rats were then randomly divided into 3 groups and received a special diet supplemented with casein (control), low-isoflavone soy (LIS) protein, and high-isoflavone soy protein (HIS) for 8 weeks. Compared with the control or LIS groups, those rats on the HIS diet had significantly increased body weight and serum insulin levels and reduced serum glucose and methylglyoxal levels. Serum glutathione levels were also increased in rats given the HIS diet compared with those in the control or LIS (P < .01). Serum high-density lipoprotein cholesterol level was significantly higher in HIS-fed rats than that of the control or LIS rats (P < .05). More importantly, the death rate and incidence of cataracts in the diabetic rats were markedly decreased in the HIS group. In conclusion, ingestion of high-isoflavone soy protein not only lowers glucose levels but also reduces the incidence of cataracts in diabetic rats. The beneficial effects of soy isoflavones are attributed to increased insulin secretion, a better glycemic control, and antioxidant protection.

  7. Biochemical and immunohistochemical changes in delta-9-tetrahydrocannabinol-treated type 2 diabetic rats.

    PubMed

    Coskun, Zeynep Mine; Bolkent, Sema

    2014-01-01

    The regulation of glucose, lipid metabolism and immunoreactivities of insulin and glucagon peptides by delta-9-tetrahydrocannabinol (Δ(9)-THC) in diabetes were examined in an experimental rat model. Male Sprague-Dawley rats were divided into four groups: (1) control, (2) Δ(9)-THC treated, (3) diabetic, and (4) diabetic+Δ(9)-THC. The type 2 diabetic rat model was established by intraperitoneal (i.p.) injection of nicotinamide (85 mg/kg body weight) followed after 15 min by i.p. injection of streptozotocin (STZ) at 65 mg/kg of body weight. Δ(9)-THC and Δ(9)-THC treated diabetic groups received 3mg/kg/day of Δ(9)-THC for 7 days. The immunolocalization of insulin and glucagon peptides was investigated in the pancreas using a streptavidin-biotin-peroxidase technique. High density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL), triglycerides (TG), total cholesterol (TC) and total protein (TP) levels were measured in serum. Total islet area percent of insulin immunoreactive cells slightly changed in diabetic+Δ(9)-THC rats compared to diabetic animals. However, the area percent of glucagon immunoreactive cells showed a decrease in diabetic+Δ(9)-THC rats compared to that of diabetic animals alone. Serum TC, HDL and LDL levels of diabetes+Δ(9)-THC group showed a decrease compared to the diabetic group. These results indicate that Δ(9)-THC may serve a protective role against hyperlipidemia and hyperglycemia in diabetic rats.

  8. The protective effects of silibinin in the treatment of streptozotocin-induced diabetic osteoporosis in rats.

    PubMed

    Wang, Te; Cai, Leyi; Wang, Yangyang; Wang, Qingqing; Lu, Di; Chen, Hua; Ying, Xiaozhou

    2017-03-05

    Diabetic osteoporosis (DO) is a complication of diabetes mellitus. Our previous study showed that silibinin can attenuate high glucose mediated human bone marrow stem cells dysfunction through antioxidant effect. However, no study has yet investigated the effect of silibinin in diabetic rats. Therefore, we assessed the effects of silibinin on bone characteristics in streptozotocin-induced diabetic rats. The aim of our study was to determine whether providing silibinin in the different supplementation could prevent bone loss in diabetic rats or not. Rats were randomly divided into four groups: (1) control group (CG) (n=10); (2) diabetic group (DG) (n=10); (3) diabetic group with 50mgkg(-1)day(-1) of silibinin orally (DG-50) (n=10); and (4) diabetic group with 100mgkg(-1)day(-1) of silibinin orally (DG-100) (n=10). 12 weeks after streptozotocin (STZ) injection, the femora from all rats were assessed and oxidative stress was evaluated. Bone mineral density was significantly decreased in diabetic rats; these effects were prevented by treatment with silibinin (100mgkg(-1)day(-1) orally). Similarly, in the DG and DG-50 groups, changes in microarchitecture of femoral metaphysis assessed by microcomputed tomography demonstrated simultaneous existence of diabetic osteoporosis; these impairments were prevented by silibinin (100mgkg(-1)day(-1) orally). In conclusion, silibinin supplementation may have potential use as a possible therapy for maintaining skeletal health and these results can enhance the understanding of diabetic osteoporosis induced by diabetes.

  9. Pregnant diabetic rats fed the antioxidant butylated hydroxytoluene show decreased occurrence of malformations in offspring.

    PubMed

    Eriksson, U J; Simán, C M

    1996-11-01

    The increased incidence of congenital malformations in diabetic pregnancy may be associated with an excess of free oxygen radicals in the embryo. We have previously blocked the dysmorphogenesis of rat embryos exposed to high glucose and beta-hydroxybutyrate concentrations in vitro by increasing the antioxidant capacity of the conceptus. In the present study, we attempted to diminish the teratogenic process in vivo in a rat model of diabetic pregnancy. Thus, pregnant diabetic and normal rats were fed either a standard diet or a diet enriched with 1% of the antioxidant butylated hydroxytoluene (BHT). The fetuses of the diabetic rats were smaller than the fetuses of the normal rats (body weight 2.70 g vs. 3.68 g) when the mothers were fed a standard diet. The BHT diet increased the fetal weight in the offspring of diabetic rats (3.17 g), with no change in fetuses of the normal rats (3.65 g). The placentas of diabetic rats were heavier than the placentas of normal rats; this difference was not present in the BHT-fed rats. The BHT treatment had no effect on the rate of resorptions, which was increased in the diabetic rats compared with the normal rats. In contrast, the increased rate of congenital malformations in the offspring of diabetic rats (19%), compared with that in the normal rats (0%), was markedly decreased by the BHT diet (2.3%). No malformations were found in the normal rats treated with BHT. These data support the notion that an excess of free oxygen radicals in the embryo contributes to the teratogenic process of diabetic pregnancy and, thus, suggest an area for future preventive therapeutic treatment.

  10. Evaluation of treadmill exercise effect on muscular lipid profiles of diabetic fatty rats by nanoflow liquid chromatography–tandem mass spectrometry

    NASA Astrophysics Data System (ADS)

    Lee, Jong Cheol; Kim, Il Yong; Son, Yeri; Byeon, Seul Kee; Yoon, Dong Hyun; Son, Jun Seok; Song, Han Sol; Song, Wook; Seong, Je Kyung; Moon, Myeong Hee

    2016-07-01

    We compare comprehensive quantitative profiling of lipids at the molecular level from skeletal muscle tissues (gastrocnemius and soleus) of Zucker diabetic fatty rats and Zucker lean control rats during treadmill exercise by nanoflow liquid chromatography–tandem mass spectrometry. Because type II diabetes is caused by decreased insulin sensitivity due to excess lipids accumulated in skeletal muscle tissue, lipidomic analysis of muscle tissues under treadmill exercise can help unveil the mechanism of lipid-associated insulin resistance. In total, 314 lipid species, including phospholipids, sphingolipids, ceramides, diacylglycerols (DAGs), and triacylglycerols (TAGs), were analyzed to examine diabetes-related lipid species and responses to treadmill exercise. Most lysophospholipid levels increased with diabetes. While DAG levels (10 from the gastrocnemius and 13 from the soleus) were >3-fold higher in diabetic rats, levels of most of these decreased after exercise in soleus but not in gastrocnemius. Levels of 5 highly abundant TAGs (52:1 and 54:3 in the gastrocnemius and 48:2, 50:2, and 52:4 in the soleus) displaying 2-fold increases in diabetic rats decreased after exercise in the soleus but not in the gastrocnemius in most cases. Thus, aerobic exercise has a stronger influence on lipid levels in the soleus than in the gastrocnemius in type 2 diabetic rats.

  11. Evaluation of treadmill exercise effect on muscular lipid profiles of diabetic fatty rats by nanoflow liquid chromatography–tandem mass spectrometry

    PubMed Central

    Lee, Jong Cheol; Kim, Il Yong; Son, Yeri; Byeon, Seul Kee; Yoon, Dong Hyun; Son, Jun Seok; Song, Han Sol; Song, Wook; Seong, Je Kyung; Moon, Myeong Hee

    2016-01-01

    We compare comprehensive quantitative profiling of lipids at the molecular level from skeletal muscle tissues (gastrocnemius and soleus) of Zucker diabetic fatty rats and Zucker lean control rats during treadmill exercise by nanoflow liquid chromatography–tandem mass spectrometry. Because type II diabetes is caused by decreased insulin sensitivity due to excess lipids accumulated in skeletal muscle tissue, lipidomic analysis of muscle tissues under treadmill exercise can help unveil the mechanism of lipid-associated insulin resistance. In total, 314 lipid species, including phospholipids, sphingolipids, ceramides, diacylglycerols (DAGs), and triacylglycerols (TAGs), were analyzed to examine diabetes-related lipid species and responses to treadmill exercise. Most lysophospholipid levels increased with diabetes. While DAG levels (10 from the gastrocnemius and 13 from the soleus) were >3-fold higher in diabetic rats, levels of most of these decreased after exercise in soleus but not in gastrocnemius. Levels of 5 highly abundant TAGs (52:1 and 54:3 in the gastrocnemius and 48:2, 50:2, and 52:4 in the soleus) displaying 2-fold increases in diabetic rats decreased after exercise in the soleus but not in the gastrocnemius in most cases. Thus, aerobic exercise has a stronger influence on lipid levels in the soleus than in the gastrocnemius in type 2 diabetic rats. PMID:27388225

  12. [Effect of taurine and thioctacide on carbohydrate metabolism and the antioxydant system in rats with experimental diabetes].

    PubMed

    Gavrovskaia, L K; Ryzhova, O V; Safonova, A F; Aleksandrova, I Ia; Sapronov, N S

    2008-01-01

    Peroral administration of taurine and thioctacide in rats with alloxan-induced diabetes (i) decreased the levels of glucose, fructosamine and MDA, (ii) increased the levels of glycogen, insulin, and C-peptide in the liver, and (iii) increased the levels of enzymes of the antioxidant system of catalase and paraoxonase as compared to the control group of animals. These effects show that taurine and thioctacide possess hypoglycemic and antioxidant properties.

  13. Raloxifene prevents skeletal fragility in adult female Zucker Diabetic Sprague-Dawley rats.

    PubMed

    Hill Gallant, Kathleen M; Gallant, Maxime A; Brown, Drew M; Sato, Amy Y; Williams, Justin N; Burr, David B

    2014-01-01

    Fracture risk in type 2 diabetes is increased despite normal or high bone mineral density, implicating poor bone quality as a risk factor. Raloxifene improves bone material and mechanical properties independent of bone mineral density. This study aimed to determine if raloxifene prevents the negative effects of diabetes on skeletal fragility in diabetes-prone rats. Adult Zucker Diabetic Sprague-Dawley (ZDSD) female rats (20-week-old, n = 24) were fed a diabetogenic high-fat diet and were randomized to receive daily subcutaneous injections of raloxifene or vehicle for 12 weeks. Blood glucose was measured weekly and glycated hemoglobin was measured at baseline and 12 weeks. At sacrifice, femora and lumbar vertebrae were harvested for imaging and mechanical testing. Raloxifene-treated rats had a lower incidence of type 2 diabetes compared with vehicle-treated rats. In addition, raloxifene-treated rats had blood glucose levels significantly lower than both diabetic vehicle-treated rats as well as vehicle-treated rats that did not become diabetic. Femoral toughness was greater in raloxifene-treated rats compared with both diabetic and non-diabetic vehicle-treated ZDSD rats, due to greater energy absorption in the post-yield region of the stress-strain curve. Similar differences between groups were observed for the structural (extrinsic) mechanical properties of energy-to-failure, post-yield energy-to-failure, and post-yield displacement. These results show that raloxifene is beneficial in preventing the onset of diabetes and improving bone material properties in the diabetes-prone ZDSD rat. This presents unique therapeutic potential for raloxifene in preserving bone quality in diabetes as well as in diabetes prevention, if these results can be supported by future experimental and clinical studies.

  14. Camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats.

    PubMed

    Meena, Sunita; Rajput, Yudhishthir S; Pandey, Amit K; Sharma, Rajan; Singh, Raghvendar

    2016-08-01

    This study was designed to assess anti-diabetic potential of goat, camel, cow and buffalo milk in streptozotocin (STZ) induced type 1 diabetic albino wistar rats. A total of 48 rats were taken for the study where one group was kept as non-diabetic control group (8 rats) while others (40 rats) were made diabetic by STZ (50 mg/kg of body weight) injection. Among diabetic rats, a control group (8 rats) was kept and referred as diabetic control whereas other four groups (8 rats each) of diabetic rats were fed on 50 ml of goat or camel or cow or buffalo milk for 4 weeks. All the rats (non-diabetic and diabetic) were maintained on standard diet for four weeks. STZ administration resulted in enhancement of glucose, total cholesterol, triglyceride, low density lipoprotein, HbA1c and reduction in high density lipoprotein in plasma and lowering of antioxidative enzymes (catalase, glutathione peroxidase and superoxide dismutase) activities in pancreas, kidney, liver and RBCs, coupled with enhanced levels of TBARS and protein carbonyls in pancreas, kidney, liver and plasma. OGTT carried out at the end of 4 week milk feeding indicated that all milks helped in early maintenance of glucose level. All milks reduced atherogenic index. In camel milk fed diabetic group, insulin concentration enhanced to level noted for non-diabetic control while goat, cow and buffalo milk failed to restore insulin level. HbA1c level was also restored only in camel milk fed diabetic group. The level of antioxidative enzymes (catalase, GPx and SOD) in pancreas enhanced in all milk fed groups. Camel milk and to a reasonable extent goat milk reduced formation of TBARS and PCs in tissues and blood. It can be concluded that camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats. Further, only camel milk completely ameliorated oxidative damage in pancreas and normalised insulin level.

  15. Effect of Mucuna pruriens (Linn.) on sexual behavior and sperm parameters in streptozotocin-induced diabetic male rat.

    PubMed

    Suresh, Sekar; Prakash, Seppan

    2012-12-01

    Sexual dysfunction is one of the major secondary complications in the diabetic. Mucuna pruriens, a leguminous plant identified for its antidiabetic, aphrodisiac, and improving fertility properties, has been the choice of Indian traditional medicine. Objective of the present study was to analyze the efficacy of M. pruriens on male sexual behavior and sperm parameters in long-term hyperglycemic male rats. Male albino rats were divided as group I control, group II diabetes induced (streptozotocin [STZ] 60 mg/kg of body weight (b.w.) in 0.1 M citrate buffer), group III diabetic rats administered with 200 mg/kg b.w. of ethanolic extract of M. pruriens seed, group IV diabetic rats administered with 5 mg/kg b.w. of sildenafil citrate (SC), group V administered with 200 mg/kg b.w. of extract, and group VI administered with 5 mg/kg b.w. of SC. M. pruriens and SC were administered in single oral dosage per day for a period of 60 days. The animals were subjected to mating behavior analyses, libido, test of potency, and epididymal sperms were analyzed. The mating behavior, libido, test of potency, along with epididymal sperms were studied. The study showed significant reduction in sexual behavior and sperm parameters in group II. Daily sperm production (DSP) and levels of follicular stimulating hormone, luteinizing hormone, and testosterone were significantly reduced in group II, whereas the animals with diabetes administered with seed extract of M. pruriens (group III) showed significant improvement in sexual behavior, libido and potency, sperm parameters, DSP, and hormonal levels when compared to group II. The present work reveals the potential efficacy of ethanolic seed extract of M. pruriens to improve male sexual behavior with androgenic and antidiabetic effects in the STZ-induced diabetic male rats. This study supports the usage of M. pruriens in the Indian system of medicine as sexual invigorator in diabetic condition and encourages performing similar study in men.

  16. Effects of Cinnamomum zeylanicum (Ceylon cinnamon) on blood glucose and lipids in a diabetic and healthy rat model

    PubMed Central

    Ranasinghe, Priyanga; Perera, Sanja; Gunatilake, Mangala; Abeywardene, Eranga; Gunapala, Nuwan; Premakumara, Sirimal; Perera, Kamal; Lokuhetty, Dilani; Katulanda, Prasad

    2012-01-01

    Objectives: To evaluate short- and long-term effects of Cinnamomum zeylanicum on food consumption, body weight, glycemic control, and lipids in healthy and diabetes-induced rats. Materials and Methods: The study was conducted in two phases (Phase I and Phase II), using Sprague-Dawley rats in four groups. Phase I evaluated acute effects on fasting blood glucose (FBG) (Groups 1 and 2) and on post-oral glucose (Groups 3 and 4) blood glucose. Groups 1 and 3 received distilled-water and Groups 2 and 4 received cinnamon-extracts. Phase II evaluated effects on food consumption, body weight, blood glucose, and lipids over 1 month. Group A (n = 8, distilled-water) and Group B (n = 8, cinnamon-extracts) were healthy rats, while Group C (n = 5, distilled-water) and Group D (n = 5, cinnamon-extracts) were diabetes-induced rats. Serum lipid profile and HbA1c were measured on D-0 and D-30. FBG, 2-h post-prandial blood glucose, body weight, and food consumption were measured on every fifth day. Results: Phase I: There was no significant difference in serial blood glucose values in cinnamon-treated group from time 0 (P > 0.05). Following oral glucose, the cinnamon group demonstrated a faster decline in blood glucose compared to controls (P < 0.05). Phase II: Between D0 and D30, the difference in food consumption was shown only in diabetes-induced rats (P < 0.001). Similarly, the significant difference following cinnamon-extracts in FBG and 2-h post-prandial blood glucose from D0 to D30 was shown only in diabetes-induced rats. In cinnamon-extracts administered groups, total and LDL cholesterol levels were lower on D30 in both healthy and diabetes-induced animals (P < 0.001). Conclusions: C. zeylanicum lowered blood glucose, reduced food intake, and improved lipid parameters in diabetes-induced rats. PMID:22518078

  17. Interaction between Sex and Social Support in the Control of Type II Diabetes Mellitus.

    ERIC Educational Resources Information Center

    Heitzmann, Carma A.; Kaplan, Robert M.

    1984-01-01

    Investigated the role of social support in the control of Type II diabetes mellitus. Participants (N=37) in a behavioral program in diabetes care completed questionnaires and provided blood samples. For women, satisfaction with supportive relationships was associated with control of diabetes. The opposite was true for men. (BH)

  18. Interaction between Sex and Social Support in the Control of Type II Diabetes Mellitus.

    ERIC Educational Resources Information Center

    Heitzmann, Carma A.; Kaplan, Robert M.

    1984-01-01

    Investigated the role of social support in the control of Type II diabetes mellitus. Participants (N=37) in a behavioral program in diabetes care completed questionnaires and provided blood samples. For women, satisfaction with supportive relationships was associated with control of diabetes. The opposite was true for men. (BH)

  19. Antihyperlipidemic effect of fisetin, a bioflavonoid of strawberries, studied in streptozotocin-induced diabetic rats.

    PubMed

    Prasath, Gopalan Sriram; Subramanian, Sorimuthu Pillai

    2014-10-01

    Chronic hyperglycemia in diabetes is associated with profound changes in lipid and lipoprotein metabolism, with resultant alterations in particle distribution within lipoprotein classes. In the present study, an attempt has been made to explore the antihyperlipidemic effect of fisetin in streptozotocin-induced experimental diabetes in rats. Upon fisetin treatment to diabetic rats, the levels of blood glucose were significantly reduced with an improvement in plasma insulin. The increased levels of lipid contents in serum, hepatic, and renal tissues observed in diabetic rats were normalized upon fisetin administration. Also, the decreased levels of high-density lipoprotein cholesterol, and increased levels of low-density lipoprotein (LDL) and very LDL (VLDL) cholesterol in serum of diabetic rats were normalized. Oil Red O staining established a large number of intracellular lipid droplets accumulation in the diabetic rats. Fisetin treatment exacerbated the degree of lipid accumulation. The results of the present study exemplify the antihyperlipidemic property of the fisetin. © 2014 Wiley Periodicals, Inc.

  20. Injury to the endothelial surface layer induces glomerular hyperfiltration rats with early-stage diabetes.

    PubMed

    Zhang, Chunyang; Meng, Yao; Liu, Qi; Xuan, Miao; Zhang, Lanyu; Deng, Bo; Zhang, Keqin; Liu, Zhimin; Lei, Tao

    2014-01-01

    Glomerular endothelial surface layer (ESL) may play a role in the mechanisms of albuminuria in diabetic nephropathy, which lack evidence in vivo. The effects of high glucose on the passage of albumin across the glomerular ESL were analysed in streptozotocin-induced diabetic Sprague-Dawley rats for 4 weeks. Albuminuria and glomerular mesangial matrix were significantly increased in diabetic rats. The passage of albumin across the ESL, as measured by albumin-colloid gold particle density in the glomerular basement membrane (GBM), was increased significantly in diabetic rats. The thickness of the glomerular ESL, examined indirectly by infusing Intralipid into vessels using an electron microscope, was significantly decreased and the GBM exhibited little change in diabetic rats. In summary, the glomerular ESL may play a role in the pathogenesis of albuminuria in rats with early-stage diabetes.

  1. Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat.

    PubMed

    Sampath, Sathish; Karundevi, Balasubramanian

    2014-10-01

    Troxerutin is a trihydroxyethylated derivative of the flavonoid, rutin. It has been reported to possess the hepatoprotective, nephroprotective, antioxidant, anti-inflammatory, and antihyperlipidemic activities. Troxerutin treatment reduced the blood glucose and glycosylated hemoglobin levels in high-cholesterol-induced insulin-resistant mice and in type-2 diabetic patients. However, the mechanism by which it exhibits antidiabetic property was unknown. Therefore, the present study was designed to evaluate the effect of troxerutin on insulin signaling molecules in gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic rats. Wistar male albino rats were selected and divided into five groups. Group I: Control. Group II: High fat and sucrose-induced type-2 diabetic rats. Group III: Type-2 diabetic rats treated with troxerutin (150 mg/kg body weight/day orally). Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg body weight/day orally). Group V: Normal rats treated with troxerutin (150 mg/kg body weight/day orally). After 30 days of treatment, fasting blood glucose, oral glucose tolerance, serum lipid profile, and the levels of insulin signaling molecules, glycogen, glucose uptake, and oxidation in gastrocnemius muscle were assessed. Diabetic rats showed impairment in insulin signaling molecules (IR, p-IRS-1(Tyr632), p-Akt(Ser473), β-arrestin-2, c-Src, p-AS160(Thr642), and GLUT4 proteins), glycogen concentration, glucose uptake, and oxidation. Oral administration of troxerutin showed near normal levels of blood glucose, serum insulin, lipid profile, and insulin signaling molecules as well as GLUT4 proteins in type-2 diabetic rats. It is concluded from the present study that troxerutin may play a significant role in the management of type-2 diabetes mellitus, by improving the insulin signaling molecules and glucose utilization in the skeletal muscle.

  2. Effect of captopril and the bradykinin-PKC pathway on ROS production in type 1 diabetic rats.

    PubMed

    Rodrigues de Araujo, Glaucy; Granato de Faria, Karine; Lima, Wanderson Geraldo; Pádua, Bruno da Cruz; Rossoni, Joamyr Victor; Souza, Aline Arlindo; Chianca-Júnior, Deoclecio; Silva, Marcelo Eustáquio; Pedrosa, Maria Lucia; Chaves, Miriam Martins; Costa, Daniela Caldeira

    2011-12-01

    The aim of this study was to investigate the possible effects of captopril as a promoter in modulating the oxidant-antioxidant balance in rats with type 1 diabetes, and the influence of protein kinase C (PKC) pathways in the production of reactive oxygen species (ROS) induced by bradykinin in type 1 diabetic rats. This study evaluated the redox status in both the cardiac tissue and at the cellular level (neutrophils). Two concentrations of captopril were utilized: (i) 5 mg·(kg body mass)(-1), which was considered a therapeutic dose; and (ii) 10 mg·(kg body mass)(-1). Body mass, plasma glucose, and serum insulin were evaluated. To investigate the redox status of the cardiac tissue, we analyzed lipid peroxidation, concentration of carbonylated protein, catalase activity, and the concentration of glutathione. For a more accurate assessment of the possible antioxidant effect of captopril, we also analyzed ROS in neutrophils (in vivo), and ROS production induced by bradykinin and the influence of the PKC pathway in this production (in vitro). Our data show that the hearts of diabetic animals have increased oxidative damage, exemplified by the increased concentration of carbonylated protein and thiobarbituric acid reactive substances (TBARS). However, animals treated with captopril at both concentrations showed lower concentrations of carbonylated protein compared with untreated diabetic animals. We found an increase of catalase activity in the heart of diabetic rats, which was reversed by captopril treatment at both of the dosages tested. Our data showed that captopril was able to reduce ROS production in the neutrophils of diabetic rats at a dose of 10 mg captopril·(kg body mass)(-1). However, the antioxidant effect of captopril is independent of bradykinin. Diabetes induces oxidative stress, and these results suggest that captopril has an antioxidant effect and can modulate the production of ROS in circulating neutrophils.

  3. METHYLENE BLUE IMPROVES MITOCHONDRIAL RESPIRATION AND DECREASES OXIDATIVE STRESS IN A SUBSTRATE-DEPENDENT MANNER IN DIABETIC RAT HEARTS.

    PubMed

    Duicu, Oana M; Privistirescu, Andreea; Wolf, Adrian; Petrus, Alexandra; Dănilă, Maria D; Ratiu, Corina; Muntean, Danina M; Sturza, Adrian

    2017-07-24

    Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox-drug with reported protective effects mainly on brain mitochondria. The present study was purported to characterize the effects of acute administration of methylene blue on mitochondrial respiration, H2O2 production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats. Mitochondrial respiratory function was assessed by high-resolution respirometry. Hydrogen peroxide production and calcium retention capacity were measured spectrofluorimetrically. The addition of methylene blue (0.1 μM) elicited an increase in oxygen consumption of mitochondria energized with complex I and II substrates in both normal and diseased mitochondria. Interestingly, methylene blue elicited a significant increase in H2O2 release in the presence of CI substrates (glutamate-malate), but had an opposite effect in mitochondria energized with CII substrate (succinate). No changes in the calcium retention capacity of healthy or diabetic mitochondria were found in the presence of methylene blue. In conclusion, in cardiac mitochondria isolated from diabetic and non-diabetic rat hearts, methylene blue improved respiratory function and elicited a dichotomic, substrate-dependent effect on ROS production.

  4. Altered glucose kinetics in diabetic rats during Gram-negative infection

    SciTech Connect

    Lang, C.H.; Dobrescu, C.; Bagby, G.J.; Spitzer, J.J. )

    1987-08-01

    The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced severe diabetes, whereas the lower dose of streptozotocin produced a miler, latent diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats. Thus the present study suggests that the imposition of nonlethal Gram-negative sepsis on severe diabetic animals does not further impair glucose homeostasis and that the milder latent diabetes was not converted to a more severe diabetic state by the septic challenge.

  5. Regulation of podocalyxin expression in the kidney of streptozotocin-induced diabetic rats with Chinese herbs (Yishen capsule).

    PubMed

    Fang, Jingai; Wei, Hongkun; Sun, Yanyan; Zhang, Xiaodong; Liu, Wenyuan; Chang, Qintao; Wang, Ruihua; Gong, Yuewen

    2013-04-05

    Diabetic nephropathy is an emergent issue in China with increase in patients with type II diabetes. There are several successful Chinese herbal products for the treatment of patients with diabetic nephropathy in China. However, the mechanisms mediating the biological activity of these products are still unclear. Podocalyxin is a sialoprotein critical to maintaining integrity of filtration function of glomerulus. By employing streptozotocin-induced diabetic rats and a Chinese herb formulation (Yishen capsule), we examined the regulation of podocalyxin expression in the kidney by Yishen capsule through immunofluorescent staining and reverse transcriptase polymerase chain reaction. After injection of STZ, there were significant increase in both blood glucose and urinary protein. Serum creatinine and BUN were also increased in rats with injection of STZ. Moreover, expression of podocalyxin in the glomerulus was gradually reduced after injection of STZ. There was also a loss of podocyte foot processes in the glomerular basement membrane. However, Yishen capsule or benazepril was able to restore the expression of podocalyxin and podocyte foot processes in the kidney. Although Yishen capsule could reduce urinary protein level, it has little effect on blood glucose level in the rats injected with STZ. Yishen capsule could attenuate the loss of podocalyxin in the glomerulus of rats injected with STZ.

  6. Antidiabetic Effect of Sida cordata in Alloxan Induced Diabetic Rats

    PubMed Central

    Shah, Naseer Ali; Khan, Muhammad Rashid

    2014-01-01

    Medicinal plants are efficient ameliorator of oxidative stress associated with diabetes mellitus. In this study, ethyl acetate fraction (SCEE) of Sida cordata was investigated for scientific validation of its folk use in diabetes. Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal glucose loaded and diabetic glucose loaded animals as well as normal off feed animals. Confirmation of antidiabetic activity and toxicity ameliorative role of S. cordata was investigated in a chronic multiple dose treatment study of fifteen days. A single dose of alloxan (120 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides, and cholesterol and decreased the high-density lipoproteins. Concurrent with these changes, there was an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite in pancreas, liver, and testis. This oxidative stress was related to a decrease in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for 15 days after diabetes induction ameliorated hyperglycemia, restored lipid profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated the GSH production in the organs of alloxan-treated rats. We suggested that SCEE could be used as antidiabetic component in case of diabetes mellitus. This may be related to its antioxidative properties. PMID:25114914

  7. Antidiabetic effect of Sida cordata in alloxan induced diabetic rats.

    PubMed

    Shah, Naseer Ali; Khan, Muhammad Rashid

    2014-01-01

    Medicinal plants are efficient ameliorator of oxidative stress associated with diabetes mellitus. In this study, ethyl acetate fraction (SCEE) of Sida cordata was investigated for scientific validation of its folk use in diabetes. Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal glucose loaded and diabetic glucose loaded animals as well as normal off feed animals. Confirmation of antidiabetic activity and toxicity ameliorative role of S. cordata was investigated in a chronic multiple dose treatment study of fifteen days. A single dose of alloxan (120 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides, and cholesterol and decreased the high-density lipoproteins. Concurrent with these changes, there was an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite in pancreas, liver, and testis. This oxidative stress was related to a decrease in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for 15 days after diabetes induction ameliorated hyperglycemia, restored lipid profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated the GSH production in the organs of alloxan-treated rats. We suggested that SCEE could be used as antidiabetic component in case of diabetes mellitus. This may be related to its antioxidative properties.

  8. Rat1p maintains RNA polymerase II CTD phosphorylation balance

    PubMed Central

    Jimeno-González, Silvia; Schmid, Manfred; Malagon, Francisco; Haaning, Line Lindegaard; Jensen, Torben Heick

    2014-01-01

    In S. cerevisiae, the 5′-3′ exonuclease Rat1p partakes in transcription termination. Although Rat1p-mediated RNA degradation has been suggested to play a role for this activity, the exact mechanisms by which Rat1p helps release RNA polymerase II (RNAPII) from the DNA template are poorly understood. Here we describe a function of Rat1p in regulating phosphorylation levels of the C-terminal domain (CTD) of the largest RNAPII subunit, Rpb1p, during transcription elongation. The rat1-1 mutant exhibits highly elevated levels of CTD phosphorylation as well as RNAPII distribution and transcription termination defects. These phenotypes are all rescued by overexpression of the CTD phosphatase Fcp1p, suggesting a functional relationship between the absence of Rat1p activity, elevated CTD phosphorylation, and transcription defects. We also demonstrate that rat1-1 cells display increased RNAPII transcription kinetics, a feature that may contribute to the cellular phenotypes of the mutant. Consistently, the rat1-1 allele is synthetic lethal with the rpb1-E1103G mutation, causing increased RNAPII speed, and is suppressed by the rpb2-10 mutation, causing slowed transcription. Thus, Rat1p plays more complex roles in controlling transcription than previously thought. PMID:24501251

  9. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: Study in vasopressin-deficient Brattleboro rats

    PubMed Central

    Bardoux, Pascale; Martin, Hélène; Ahloulay, Mina; Schmitt, François; Bouby, Nadine; Trinh-Trang-Tan, Marie-Marcelle; Bankir, Lise

    1999-01-01

    Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattleboro rats with diabetes insipidus (DI) lacking VP and in normal Long-Evans (LE) rats, with or without streptozotocin-induced DM. Blood and urine were collected after 2 and 4 weeks of DM, and creatinine clearance, urinary glucose and albumin excretion, and kidney weight were measured. Plasma glucose increased 3-fold in DM rats of both strains, but glucose excretion was ≈40% lower in DI-DM than in LE-DM, suggesting less intense metabolic disorders. Creatinine clearance increased significantly in LE-DM (P < 0.01) but failed to increase in DI-DM. Urinary albumin excretion more than doubled in LE-DM but rose by only 34% in DI-DM rats (P < 0.05). Kidney hypertrophy was also less intense in DI-DM than in LE-DM (P < 0.001). These results suggest that VP plays a critical role in diabetic hyperfiltration and albuminuria induced by DM. This hormone thus seems to be an additional risk factor for diabetic nephropathy and, thus, a potential target for prevention and/or therapeutic intervention. PMID:10468619

  10. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: study in vasopressin-deficient Brattleboro rats.

    PubMed

    Bardoux, P; Martin, H; Ahloulay, M; Schmitt, F; Bouby, N; Trinh-Trang-Tan, M M; Bankir, L

    1999-08-31

    Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattleboro rats with diabetes insipidus (DI) lacking VP and in normal Long-Evans (LE) rats, with or without streptozotocin-induced DM. Blood and urine were collected after 2 and 4 weeks of DM, and creatinine clearance, urinary glucose and albumin excretion, and kidney weight were measured. Plasma glucose increased 3-fold in DM rats of both strains, but glucose excretion was approximately 40% lower in DI-DM than in LE-DM, suggesting less intense metabolic disorders. Creatinine clearance increased significantly in LE-DM (P < 0.01) but failed to increase in DI-DM. Urinary albumin excretion more than doubled in LE-DM but rose by only 34% in DI-DM rats (P < 0.05). Kidney hypertrophy was also less intense in DI-DM than in LE-DM (P < 0.001). These results suggest that VP plays a critical role in diabetic hyperfiltration and albuminuria induced by DM. This hormone thus seems to be an additional risk factor for diabetic nephropathy and, thus, a potential target for prevention and/or therapeutic intervention.

  11. Effects of long-acting somatostatin analogues on redox systems in rat lens in experimental diabetes

    PubMed Central

    Kunjara, Sirilaksana; Greenbaum, A Leslie; Sochor, Milena; Flyvbjerg, Allan; Grønbaek, Henning; McLean, Patricia

    2014-01-01

    The effects of long-acting somatostatin analogues, angiopeptin (AGP) and Sandostatin (SMS), on the early decline in the lens content of glutathione (GSH), ATP and NADPH and increase in sorbitol were studied in STZ diabetic rats, and comparison was made with the effect of insulin. Three factors prompted this study: (i) the known increase in IGF-1 in ocular tissue in diabetes and antagonistic effect of somatostatins, (ii) the known effect of IGF-1 in increasing lens aldose reductase and (iii) the lack of effect of somatostatins on diabetic hyperglycaemia, the latter enabling a differentiation to be made between effects of hyperglycaemia per se and site(s) of IGF-1/somatostatins. All four metabolites studied showed a significant restoration towards the normal control level after 7 days of treatment with AGP and SMS, and AGP was more effective on levels of GSH and ATP. A significant correlation was found between GSH and ATP across all groups at 7 days treatment. The redox state changes in diabetes include both NADP+/NADPH and NAD+/NADH in the conversion of glucose to sorbitol and via sorbitol dehydrogenase to fructose with a linked decrease in ATP formation via NAD+/NADH regulation of the glycolytic pathway. The interlinked network of change includes the requirement for ATP in the synthesis of GSH. The present study points to possible loci of action of somatostatins in improving metabolic parameters in the diabetic rat lens via effects on aldose reductase and/or glucose transport at GLUT 3. PMID:24602114

  12. Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats.

    PubMed

    Hofni, Amal; El-Moselhy, Mohamed A; Taye, Ashraf; Khalifa, Mohamed M

    2014-12-05

    Diabetic nephropathy is one of the most common causes of end-stage kidney disease. Aldosterone and angiotensin II appear to play a crucial role in the pathogenesis of this disease. The present study aimed to investigate effects of the combination therapy with spironolactone and candesartan on diabetic nephropathy and elucidate the underlying mechanism(s) involved. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg). The diabetic rats were orally treated with spironolactone (50 mg/kg/day) and/or candesartan (1 mg/kg/day) for 8 weeks. Administration of STZ caused a marked elevation in the serum level of creatinine, urea and urinary albumin-creatinine ratio (ACR). This was associated with upregulated renal protein levels of nuclear factor-kappa B (NF-κB), transforming growth factor (TGF)-β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) alongside increasing the renal superoxide anion (O2(-)) production, malondialdehyde (MDA) level and the systolic blood pressure. There was a marked decrease in nitric oxide (NO) bioavailability and antioxidant enzyme capacity. The combined therapy of spironolactone and candesartan significantly normalized the oxidative stress and fibrotic/inflammatory alterations. Additionally, the elevated blood pressure was attenuated by administration of candesartan alone or in combination. This was associated with improving the renal function parameters. The combined therapy exhibited more profound response compared to the monotherapy. In conclusion, our results demonstrate that the combined therapy of spironolactone and candesartan can confer an additive benefit over the use of either drug alone against STZ-induced diabetic nephropathy, presumably via attenuating the inflammatory responses and oxidative status markers.

  13. Rad: A member of the Ras family overexpressed in muscle of type II diabetic humans

    SciTech Connect

    Reynet, C.; Kahn, C.R. )

    1993-11-26

    To identify the gene or genes associated with insulin resistance in Type II (non-insulin-dependent) diabetes mellitus, subtraction libraries were prepared from skeletal muscle of normal and diabetic humans and screened with subtracted probes. Only one clone out of 4000 was selectively overexpressed in Type II diabetic muscle as compared to muscle of non-diabetic or Type I diabetic individuals. This clone encoded a new 290 kilodalton member of the Ras-guanosine triphosphatase superfamily and was termed Rad (Ras associated with diabetes). Messenger ribonucleic acid of Rad was expressed primarily in skeletal and cardiac muscle and was increased an average of 8.6-fold in the muscle of Type II diabetics as compared to normal individuals.

  14. Effects of sesame oil on the reproductive parameters of diabetes mellitus-induced male rats.

    PubMed

    Abbasi, Zahra; Tabatabaei, Seyed Reza Fatemi; Mazaheri, Yazdan; Barati, Farid; Morovvati, Hasan

    2013-08-01

    The purpose of the present study was to investigate the effect of sesame oil on the reproductive parameters of diabetic male Wistar rats. The adult male rats in a split plot design were divided into normal (n=10), normal 5% (n=5; 5% sesame oil enriched diet), diabetic (Streptozocin induced diabetes; n=9), diabetic 5% (n=9; 5% sesame oil enriched diet), and diabetic 10% (n=9; 10% sesame oil enriched diet) groups. Diet supplementation continued for 56 days. Sesame oil supplementation did not reduce the plasma glucose concentration of rats in the diabetic groups (p>0.05). The total spermatogonia, spermatocytes, Leydig cells/tubule, and the germ cell to Sertoli cell ratio were lower in the diabetic rats than the normal ones (p<0.05), and with the exception of spermatogonia counts, these values improved by the addition of sesame oil to the diet (p<0.05). The sperm progressive motility and viability were lower in the diabetic rats (p<0.05) and sesame oil supplementation did not improve them. Incorporation of sesame oil into the diet improved the plasma testosterone concentration of the diabetic rats in a dose-dependent manner (p<0.05). In summary, sesame oil supplementation improved the reproductive parameters of diabetic rats at the levels of the testicular microstructure and function, but was not effective in protecting the epididymal sperm.

  15. Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy

    PubMed Central

    Newton, Victoria L.; Guck, Jonathan D.; Cotter, Mary A.

    2017-01-01

    Spinal glial cell activation and cytokine secretion have been implicated in the etiology of neuropathic pain in a number of experimental models, including diabetic neuropathy. In this study, streptozotocin- (STZ-) induced diabetic rats were either untreated or treated with gabapentin (50 mg/kg/day by gavage for 2 weeks, from 6 weeks after STZ). At 8 weeks after STZ, hypersensitivity was confirmed in the untreated diabetic rats as a reduced response threshold to touch, whilst mechanical thresholds in gabapentin-treated diabetic rats were no different from controls. Diabetes-associated thermal hypersensitivity was also ameliorated by gabapentin. We performed a cytokine profiling array in lumbar spinal cord samples from control and diabetic rats. This revealed an increase in L-selectin, an adhesion molecule important for neutrophil transmigration, in the spinal cord of diabetic rats but not diabetic rats treated with gabapentin. Furthermore, we found an increase in the number of neutrophils present in the parenchyma of the spinal cord, which was again ameliorated in gabapentin-treated diabetic rats. Therefore, we suggest that dysregulated spinal L-selectin and neutrophil infiltration into the spinal cord could contribute to the pathogenesis of painful diabetic neuropathy. PMID:28293643

  16. Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting Antioxidant, Inflammatory and Aromatase Expression.

    PubMed

    Atta, Mustafa S; Almadaly, Essam A; El-Far, Ali H; Saleh, Rasha M; Assar, Doaa H; Al Jaouni, Soad K; Mousa, Shaker A

    2017-04-27

    Antioxidants have valuable effects on the process of spermatogenesis, particularly with diabetes mellitus (DM). Therefore, the present study investigated the impact and the intracellular mechanisms by which thymoquinone (TQ) works against diabetes-induced testicular deteriorations in rats. Wistar male rats (n = 60) were randomly allocated into four groups; Control, Diabetic (streptozotocin (STZ)-treated rats where diabetes was induced by intraperitoneal injection of STZ, 65 mg/kg), Diabetic + TQ (diabetic rats treated with TQ (50 mg/kg) orally once daily), and TQ (non-diabetic rats treated with TQ) for 12 weeks. Results revealed that TQ significantly improved the sperm parameters with a reduction in nitric oxide (NO) and malondialdehyde (MDA) levels in testicular tissue. Also, it increased testicular reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity. Interestingly, TQ induced downregulation of testicular inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF-κB) and significantly upregulated the aromatase protein expression levels in testicles in comparison with the diabetic rats. In conclusion, TQ treatment exerted a protective effect against reproductive dysfunction induced by diabetes not only through its powerful antioxidant and hypoglycemic effects but also through its downregulation of testicular iNOS and NF-κB along with upregulation of aromatase expression levels in diabetic rats.

  17. Resistant Starch but Not Enzymatically Modified Waxy Maize Delays Development of Diabetes in Zucker Diabetic Fatty Rats.

    PubMed

    Hedemann, Mette Skou; Hermansen, Kjeld; Pedersen, Sven; Bach Knudsen, Knud Erik

    2017-05-01

    Background: The incidence of type 2 diabetes (T2D) is increasing worldwide, and nutritional management of circulating glucose may be a strategic tool in the prevention of T2D.Objective: We studied whether enzymatically modified waxy maize with an increased degree of branching delayed the onset of diabetes in male Zucker diabetic fatty (ZDF) rats.Methods: Forty-eight male ZDF rats, aged 5 wk, were divided into 4 groups and fed experimental diets for 9 wk that contained 52.95% starch: gelatinized corn starch (S), glucidex (GLU), resistant starch (RS), or enzymatically modified starch (EMS). Blood glucose after feed deprivation was assessed every second week; blood samples taken at run-in and at the end of the experiment were analyzed for glycated hemoglobin (HbA1c) and plasma glucose, insulin, and lipids. During weeks 2 and 8, urine was collected for metabolomic analysis.Results: Based on blood glucose concentrations in feed-deprived rats, none of the groups developed diabetes. However, in week 9, plasma glucose after feed deprivation was significantly lower in rats fed the S and RS diets (13.5 mmol/L) than in rats fed the GLU and EMS diets (17.0-18.9 mmol/L), and rats fed RS had lower HbA1c (4.9%) than rats fed the S, GLU, and EMS (5.6-6.1%) diets. The homeostasis model assessment of insulin resistance was significantly lower in rats fed RS than in rats fed the other diets (185 compared with 311-360), indicating that rats fed the S, GLU, and EMS diets were diabetic, and a 100% higher urine excretion during week 8 in rats fed the GLU and EMS diets than that of rats fed S and RS showed that they were diabetic. Urinary nontargeted metabolomics revealed that the diabetic state of rats fed S, GLU, and EMS diets influenced microbial metabolism, as well as amino acid, lipid, and vitamin metabolism.Conclusions: EMS did not delay the onset of diabetes in ZDF rats, whereas rats fed RS showed no signs of diabetes. © 2017 American Society for Nutrition.

  18. Eucommia bark (Du-Zhong) improves diabetic nephropathy without altering blood glucose in type 1-like diabetic rats

    PubMed Central

    Niu, Ho-Shan; Liu, I-Min; Niu, Chiang-Shan; Ku, Po-Ming; Hsu, Chao-Tien; Cheng, Juei-Tang

    2016-01-01

    Background Eucommia bark, Eucommia ulmoides Oliver barks (Du-Zhong in Mandarin), is an herb used for renal dysfunction in Chinese traditional medicine. In an attempt to develop this herb as a treatment for diabetic nephropathy (DN), we investigated the effects of Du-Zhong on renal dysfunction in type 1-like diabetic rats. Methods Streptozotocin (STZ) was used to induce type 1-like diabetes in rats (STZ-diabetic rats). In addition to hyperglycemia, STZ-diabetic rats showed significant nephropathy, including higher plasma levels of blood urea nitrogen, creatinine, and renal fibrosis. Western blot analysis of renal cortical tissue was applied to characterize the changes in potential signals related to nephropathy. Results Oral administration of Du-Zhong (1 g/kg/day) to STZ-diabetic rats for 20 days not only decreased the plasma levels of blood urea nitrogen and creatinine but also improved renal fibrosis, whereas the plasma glucose level was not changed. The higher expressions of protein levels of transforming growth factor-beta (TGF-β) and connective tissue growth factor in diabetic rats were markedly attenuated by Du-Zhong. The increased phosphorylation of Smad2/3 in STZ-diabetic rats was also reduced by Du-Zhong. However, Du-Zhong cannot reverse the hyperglycemia-induced overproduction of signal transducers and activators of transcription 3 in the diabetic kidney. Conclusion Oral administration of Du-Zhong improves STZ-induced DN in rats by inhibiting TGF-β/Smad signaling and suppressing TGF-β/connective tissue growth factor expression. Therefore, active principle from Du-Zhong is suitable to develop as new agent for DN in the future. PMID:27041999

  19. Oxidative stress status and placental implications in diabetic rats undergoing swimming exercise after embryonic implantation.

    PubMed

    Volpato, Gustavo Tadeu; Damasceno, Débora Cristina; Sinzato, Yuri Karen; Ribeiro, Viviane Maria; Rudge, Marilza Vieira Cunha; Calderon, Iracema Mattos Paranhos

    2015-05-01

    The potential benefits and risks of physical exercise on fetal development during pregnancy remain unclear. The aim was to analyze maternal oxidative stress status and the placental morphometry to relate to intrauterine growth restriction (IUGR) from diabetic female rats submitted to swimming program after embryonic implantation. Pregnant Wistar rats were distributed into 4 groups (11 animals/group): control-nondiabetic sedentary rats, control exercised-nondiabetic exercised rats, diabetic-diabetic sedentary rats, and diabetic exercised-diabetic exercised rats. A swimming program was used as an exercise model. At the end of pregnancy, the maternal oxidative stress status, placental morphology, and fetal weight were analyzed. The swimming program was not efficient to reduce the hyperglycemia-induced oxidative stress. This fact impaired placental development, resulting in altered blood flow and energy reserves, which contributed to a deficient exchange of nutrients and oxygen for the fetal development, leading to IUGR. © The Author(s) 2014.

  20. Intracellular angiotensin II activates rat myometrium

    PubMed Central

    Deliu, Elena; Tica, Andrei A.; Motoc, Dana; Brailoiu, G. Cristina

    2011-01-01

    Angiotensin II is a modulator of myometrial activity; both AT1 and AT2 receptors are expressed in myometrium. Since in other tissues angiotensin II has been reported to activate intracellular receptors, we assessed the effects of intracellular administration of angiotensin II via microinjection on myometrium, using calcium imaging. Intracellular injection of angiotensin II increased cytosolic Ca2+ concentration ([Ca2+]i) in myometrial cells in a dose-dependent manner. The effect was abolished by the AT1 receptor antagonist losartan but not by the AT2 receptor antagonist PD-123319. Disruption of the endo-lysosomal system, but not that of Golgi apparatus, prevented the angiotensin II-induced increase in [Ca2+]i. Blockade of AT1 receptor internalization had no effect, whereas blockade of microautophagy abolished the increase in [Ca2+]i produced by intracellular injection of angiotensin II; this indicates that microautophagy is a critical step in transporting the peptide into the endo-lysosomes lumenum. The response to angiotensin II was slightly reduced in Ca2+-free saline, indicating a major involvement of Ca2+ release from internal stores. Blockade of inositol 1,4,5-trisphosphate (IP3) receptors with heparin and xestospongin C or inhibition of phospholipase C (PLC) with U-73122 abolished the response to angiotensin II, supporting the involvement of PLC-IP3 pathway. Angiotensin II-induced increase in [Ca2+]i was slightly reduced by antagonism of ryanodine receptors. Taken together, our results indicate for the first time that in myometrial cells, intracellular angiotensin II activates AT1-like receptors on lysosomes and activates PLC-IP3-dependent Ca2+ release from endoplasmic reticulum; the response is further augmented by a Ca2+-induced Ca2+ release mechanism via ryanodine receptors activation. PMID:21613610

  1. Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats.

    PubMed

    Pugliese, G; Tilton, R G; Speedy, A; Chang, K; Santarelli, E; Province, M A; Eades, D; Sherman, W R; Williamson, J R

    1989-12-01

    Rats injected i.p. with a single dose of nicotinamide (250 mg/kg) 15 min prior to i.v. injection of streptozotocin (65 mg/kg) develop a very mild form of diabetes characterized by slight elevations of plasma glucose, increased levels of HbA1, and reduced insulin secretion in response to an i.v. glucose tolerance test. These rats gain weight normally and they are not hyperphagic, glycosuric, or polyuric. The effects of this very mild form of diabetes vs overt streptozotocin diabetes of three months duration on regional vascular 131I-albumin clearance, blood flow (assessed by 15 microns 85Sr-microspheres), and renal filtration function were examined in male Sprague-Dawley rats. Plasma glucose levels of rats with mild diabetes were 7.4 +/- 0.9 (mean +/- SD) (mmol/l) vs 6.5 +/- 0.6 for control rats and 31.3 +/- 6.0 for overtly diabetic rats. HbA1 levels were increased 1.4 fold in mildly diabetic and 2.3 fold in overtly diabetic rats. Vascular clearance of 131I-albumin was markedly increased in ocular tissues (anterior uvea, retina, and choroid), sciatic nerve, aorta, new (subcutaneous) granulation tissue, and kidney of both diabetic groups, although increases in overtly diabetic rats exceeded those in the mildly diabetic group (2.2-4.6 times control animals vs 1.6-3.3 times, respectively). Likewise, both overt and very mild diabetes markedly increased glomerular filtration rate (approximately 1.8 times and 1.2 times control animals, respectively), urinary excretion of endogenous albumin (approximately 9 times and 4 times) and IgG (approximately 15 times and 4 times), as well as regional blood flow in the anterior uvea, choroid, and sciatic nerve. Increases in tissue sorbitol levels were much larger in overtly diabetic rats (generally 10-20 times control animals) than in mildly diabetic rats (1.5-3 times controls). myo-Inositol levels were significantly decreased only in lens and sciatic nerve of overtly diabetic rats. These observations indicate that even very mild

  2. 5α-Dihydrotestosterone enhances wound healing in diabetic rats.

    PubMed

    Gonçalves, Reggiani V; Novaes, Rômulo D; Sarandy, Mariáurea M; Damasceno, Eduardo M; da Matta, Sérgio L P; de Gouveia, Neire M; Freitas, Mariella B; Espindola, Foued S

    2016-05-01

    Wound healing involves a complex interaction between the cells, extracellular matrix and oxidative response. Analyze the effects of 5α-Dihydrotestosterone (5α-DTH) ointment in cutaneous wound healing by secondary intention in diabetic Wistar rats. Rats (302.23±26.23g, n=48) were maintained in cages with food and water ad libitum in accordance with the Guiding Principles in the Use of Animal Ethics Committee. Diabetes was induced by intraperitoneal injection of streptozotocin (60mg/kg). Three skin wounds (12mm diameter) were created on the animals' back, which were randomized into 6 groups according to the application received: VT group: Vehicle (lanolin), SA group: 0.9% saline solution, NC group: Non-diabetic, CP group: positive control (silver sulfadiazine 0001%), T1 group: Testosterone (10%), T2 group: Testosterone (20%) emulsified in lanolin. The applications were made daily within 21days, and tissues from different wounds were removed every 7days. Both groups treated with testosterone (T1 and T2) showed a significantly higher proportion of type I and type III collagen fibers. Superoxide dismutase levels were significantly higher on days 7 and 14 in testosterone treated groups. Protein carbonyls and MDA were lower in both groups. We conclude that groups treated with 5α-DTH showed a better healing pattern with complete wound closure, and proved to have a positive effect on the morphology of the scar tissue as well as an antioxidant stimulating effect during secondhand intention skin wounds repair in diabetic rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Effect of carnosine, aminoguanidine, and aspirin drops on the prevention of cataracts in diabetic rats

    PubMed Central

    Guo, Yong; Zhang, Jie; Ding, Zhenghua; Ha, Wenjing; Harding, J.J.

    2008-01-01

    Purpose To investigate the effect of carnosine (CA), aminoguanidine (AG), and aspirin (ASA) drops, all inhibitors of glycation, on the development of diabetic cataract in rat. Methods Rats were made diabetic with streptozotocin, and based on the level of plasma glucose, they were assigned as non-diabetic rats (<14 mmol/l plasma glucose) and diabetic rats (>14 mmol/l plasma glucose). Animals in the treated groups received CA, AG, and ASA as drops to the left eyes starting from the day of streptozotocin injection. Progression of lens opacification was recorded using the slit lamp at regular time intervals. All the rats were killed after the week 13, and the levels of advanced glycation end products (AGE), glutathione reductase (GR), catalase (CAT), and glutathione (GSH) were determined. Results Lens opacification progressed in a biphasic manner in the diabetic rats, an initial slow increase during the first eight weeks of diabetes followed by a steep increase in the next five weeks. Carnosine treatment delayed the progression of cataracts in diabetic rats, and the delay was statistically significant on the fourth week of diabetes (p<0.05, when compared with untreated moderately diabetic rats). A decrease in the antioxidant enzymes of CAT and the level of GSH was found in the lens of the untreated diabetic rats at 13 weeks after injection. Some protection was provided in the treated eyes. The level of glycation in the untreated diabetic rats was significantly higher than that in the normal rats (p<0.001). After treatment with CA, AG, and ASA, those diabetic rats had a lower level of glycated lens protein compared to the untreated diabetic rats (p<0.001). Conclusions These results thus suggest that the effect of CA, AG, and ASA is indeed inhibition of the formation of AGEs. However, the effect of CA, AG, and ASA is overwhelmed by the excessive accumulation of AGEs in the severely diabetic rats. CA compared with AG and ASA treatment can delay the progression of lens

  4. Effect of bis-1,4-dihydropyridine in the kidney of diabetic rats.

    PubMed

    Gómez-Pliego, Raquel; Gómez-Zamudio, Jaime; Velasco-Bejarano, Benjamín; Ibarra-Barajas, Maximiliano; Villalobos-Molina, Rafael

    2013-01-01

    The in vivo effectiveness of 4-dihydropyridine (bis-1,4-DHP), a new calcium-channel blocker, as a nephroprotector in isolated perfused kidney was evaluated by determining its effects on parameters associated with renal injury in diabetic rats. Diabetes in male Wistar rats, control, diabetic, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP, was induced by a single administration of STZ (55 mg·kg(-1), i.p.). In the drug-treated groups, treatment with bis-1,4-DHP (10 mg·kg(-1)·day(-1)) started one week before diabetes induction; bis-1,4-DHP was dissolved in DMSO (0.3%) and suspended in drinking water with carboxymethyl cellulose (3%). Parameters evaluated were body weight, blood glucose, albuminuria, proteinuria, creatinine, urea excretion, kidney's weight / body weight ratio, and kidney perfusion pressure in all rat groups at different times of diabetes (2, 4, 6, and 10 weeks). Kidney weight of diabetic rats significantly increased vs. control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats at different times of diabetes. The ratios % kidney weight / 100 g body weight were different between control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats vs. diabetic rats (P < 0.05). Kidney perfusion pressure was decreased by diabetes, while it was partially recovered by bis-1,4-DHP treatment in response to phenylephrine. Bis-1,4-DHP had a tendency to decrease hyperglycemia vs. diabetic rats, even though glycemia was too high as compared with controls, and it ameliorated albuminuria, creatinine, and urea excretion, suggesting a favorable effect on renal haemodynamics. Bis-1,4-DHP, by inhibiting Ca(2+) entrance, induced vasodilation in renal vascular bed and thus may have a nephroprotective effect against diabetes-induced renal dysfunction, but does not have significant impact on hyperglycemia.

  5. Type II diabetes of early onset: a distinct clinical and genetic syndrome?

    PubMed Central

    O'Rahilly, S; Spivey, R S; Holman, R R; Nugent, Z; Clark, A; Turner, R C

    1987-01-01

    The inheritance of non-insulin-dependent (type II) diabetes was studied by a continuous infusion of glucose test in all available first degree relatives of 48 diabetic probands of various ages and with differing severity of disease. In an initial study of 38 type II diabetic subjects and their first degree relatives six islet cell antibody negative patients with early onset disease (aged 25-40 at diagnosis) were found to have a particularly high familial prevalence of diabetes or glucose intolerance. Nine of 10 parents available for study either had type II diabetes or were glucose intolerant. A high prevalence of diabetes or glucose intolerance was also found in their siblings (11/16;69%). In a second study of the families of a further 10 young diabetic probands (presenting age 25-40) whose islet cell antibody state was unknown a similar high prevalence of diabetes or glucose intolerance was found among parents of the five islet cell antibody negative probands (8/9; 89%) but not among parents of the five islet cell antibody positive probands (3/8;38%). Islet cell antibody negative diabetics with early onset type II disease may have inherited a diabetogenic gene or genes from both parents. They commonly need insulin to maintain adequate glycaemic control and may develop severe diabetic complications. Early onset type II diabetes may represent a syndrome in which characteristic pedigrees, clinical severity, and absence of islet autoimmunity make it distinct from either type I diabetes, maturity onset diabetes of the young, or late onset type II diabetes. PMID:3107658

  6. Anti-diabetic properties of chromium citrate complex in alloxan-induced diabetic rats.

    PubMed

    Li, Fang; Wu, Xiangyang; Zhao, Ting; Zhang, Min; Zhao, Jiangli; Mao, Guanghua; Yang, Liuqing

    2011-12-01

    The chromium citrate complex [CrCIT] was synthesized and its structure was determined by infrared, UV-visible and atomic absorption spectroscopy, elemental and thermodynamic analysis. Anti-diabetic activity, oxidative DNA damage capacity and acute oral toxicity of [CrCIT] were investigated and compared with that of chromium trichloride hexahydrate. [CrCIT] was synthesized in a single step reaction by chelating chromium(III) with citric acid in aqueous solution. The molecular formula of [CrCIT] was inferred as CrC(6)H(5)O(7)·4H(2)O. The anti-diabetic activity of the complex [CrCIT] was assessed in alloxan-diabetic rats by daily oral gavage for 3 weeks. The biological activity results showed that the complex at the dose of 0.25-0.75 mg Cr/kg body weight could decrease the blood glucose level and increase liver glycogen level in alloxan-diabetic rats. [CrCIT] had more beneficial influences on the improvement of controlling blood glucose, serum lipid and liver glycogen levels compared with CrCl(3)·6H(2)O. Furthermore, [CrCIT] did not cause oxidative DNA damage under physiologically relevant conditions, and [CrCIT] did not produce any hazardous symptoms or deaths in acute oral toxicity test, showing the LD(50) value for female and male rats were higher than 15.1 g/kg body weight. The results suggested that [CrCIT] might represent a novel and proper chromium supplement with potential therapeutic value to control blood glucose in diabetes.

  7. A high-fat diet inhibits the progression of diabetes mellitus in type 2 diabetic rats.

    PubMed

    Ishii, Yukihito; Ohta, Takeshi; Sasase, Tomohiko; Morinaga, Hisayo; Hata, Takahiro; Miyajima, Katsuhiro; Katusda, Yoshiaki; Masuyama, Taku; Shinohara, Masami; Kakutani, Makoto; Matsushita, Mutsuyoshi

    2010-07-01

    It is well known that rats and mice, when fed a high-fat diet, develop obesity associated with abnormal glycolipid metabolism. In this study, we investigated the effects of a high-fat diet on a diabetic rat model, Spontaneously Diabetic Torii (SDT), which develops diabetes due to decreased insulin production and secretion with age. We hypothesized that a high-fat diet would accelerate the induction of diabetes in this model. The SDT rats were divided into 2 groups, which were fed a high-fat diet or standard diet for 16 weeks. The group fed a high-fat diet developed obesity, hyperinsulinemia, and hyperlipidemia until 16 weeks of age. Before 16 weeks of age, hyperglycemia accompanied by hypoinsulinemia developed in the group on a standard diet, but serum glucose levels were comparable in both groups. After 16 weeks of age, the group on a standard diet showed an increase in serum glucose levels and a decrease in serum insulin levels. Unexpectedly, in the group on the high-fat diet, we observed a suppressed of the progression of hyperglycemia/hypoinsulinemia. Histopathological observation revealed more pancreatic beta cells in the group on the high-fat diet. This study suggests that feeding SDT rats a high-fat diet induces obesity, hyperinsulinemia, and hyperlipidemia, but not hyperglycemia, until 16 weeks of age. Thereafter, age-dependent progress of hyperglycemia and hypoinsulinemia was delayed by a high-fat diet. The hyperfunction of pancreatic beta cells induced by a high-fat diet before the onset of hyperglycemia appears to suppress development of hyperglycemia/hypoinsulinemia. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Histometric assessment of the effect of diabetes mellitus on experimentally induced periodontitis in rats.

    PubMed

    Pepelassi, Eudoxie; Xynogala, Ioanna; Perrea, Despina; Agrogiannis, George; Pantopoulou, Alkistis; Patsouris, Efstratios; Vrotsos, Ioannis

    2012-04-01

    The aim of this interventional animal study was to assess histologically the effect of experimental diabetes in rats with experimental periodontitis in terms of alveolar bone loss and the effect of experimental periodontitis on glucose levels in diabetes. Forty-seven Wistar rats were studied: 12 healthy controls (C), 10 with experimental diabetes (D), 12 with experimental diabetes and experimental periodontitis (DP) and 13 with experimental periodontitis (P). Diabetes was induced by streptozotocin injection and periodontitis was induced at the right second maxillary molar by ligation. Serum glucose levels were measured at specific time points. Sixty-one days after ligation, the rats were sacrificed. Histometric analysis assessed alveolar crest level. For ligated groups, alveolar bone loss was expressed as the difference in alveolar crest level between right and left maxillary molars. Diabetes alone did not statistically significantly affect alveolar crest level. The combination of diabetes and periodontitis caused greater alveolar bone loss (946.1 +/- 719.9 microm) than periodontitis alone (639.7 +/- 294.2 microm); however, the difference did not reach statistical significance. Periodontitis did not significantly increase glucose levels in diabetic rats. The average glucose levels were 545.4 (499 - 563) and 504.5 (445 - 560) mg/dL for diabetic and diabetic ligated rats, respectively. Within its limits, this study demonstrated that the severity of alveolar bone loss in periodontitis was not significantly aggravated by diabetes and the serum glucose levels in diabetes were not affected by periodontitis.

  9. Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass.

    PubMed

    Arora, Tulika; Seyfried, Florian; Docherty, Neil G; Tremaroli, Valentina; le Roux, Carel W; Perkins, Rosie; Bäckhed, Fredrik

    2017-09-01

    Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.

  10. Angiotensin II, sodium, and cardiovascular hypertrophy in spontaneously hypertensive rats.

    PubMed

    Harrap, S B; Mitchell, G A; Casley, D J; Mirakian, C; Doyle, A E

    1993-01-01

    Angiotensin II (Ang II) may cause cardiovascular hypertrophy as a consequence of increased blood pressure or possibly by direct trophic actions. To dissociate Ang II and blood pressure in young spontaneously hypertensive rats (SHR), we used sodium loading during angiotensin converting enzyme inhibitor treatment. Animals were treated between 6 and 10 weeks of age with perindopril to lower Ang II and blood pressure, or with perindopril and 1% saline drinking fluid or perindopril and aldosterone infusion to lower Ang II but maintain high blood pressure. Blood pressure, heart weight, and media/lumen ratio of mesenteric resistance arteries were studied while rats were on treatment at 10 weeks of age and 15 weeks after treatment at 25 weeks of age. Perindopril lowered blood pressure and inhibited the development of cardiovascular hypertrophy. Saline or aldosterone restored high blood pressure during perindopril treatment and resulted in increased heart weight/body weight and resistance artery media/lumen ratios in direct proportion to the elevation of blood pressure. Because increased structure occurred despite perindopril treatment, we conclude that direct trophic actions of Ang II are not essential for the development of cardiovascular hypertrophy in young SHR and that the antitrophic actions of angiotensin converting enzyme inhibitors depend more on changes in blood pressure than on Ang II. However, restoration of blood pressure and structure by sodium during perindopril treatment raises the possibility that the design of the cardiovascular system and blood pressure may depend indirectly on Ang II through effects on sodium metabolism.

  11. Screening for Type II Diabetes Mellitus in the United States: The Present and the Future

    PubMed Central

    Abid, Ayesha; Ahmad, Shahla; Waheed, Abdul

    2016-01-01

    The number of individuals being diagnosed with type II diabetes in the United States is increasing. The screening tests for diabetes are able to detect the vast majority of diabetics. However, they do not represent the high-risk individuals who may be prone to diabetes at an earlier age. This brief communication looks at the current screening practices and the gaps in the guidelines. PMID:27330335

  12. Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice.

    PubMed

    Sidhu, G S; Mani, H; Gaddipati, J P; Singh, A K; Seth, P; Banaudha, K K; Patnaik, G K; Maheshwari, R K

    1999-01-01

    Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Interactions of different cells, extracellular matrix proteins and their receptors are involved in wound healing, and are mediated by cytokines and growth factors. Previous studies from our laboratory have shown that curcumin (diferuloylmethane), a natural product obtained from the rhizomes of Curcuma longa, enhanced cutaneous wound healing in rats and guinea pigs. In this study, we have evaluated the efficacy of curcumin treatment by oral and topical applications on impaired wound healing in diabetic rats and genetically diabetic mice using a full thickness cutaneous punch wound model. Wounds of animals treated with curcumin showed earlier re-epithelialization, improved neovascularization, increased migration of various cells including dermal myofibroblasts, fibroblasts, and macrophages into the wound bed, and a higher collagen content. Immunohistochemical localization showed an increase in transforming growth factor-beta1 in curcumin-treated wounds compared to controls. Enhanced transforming growth factor-beta1 mRNA expression in treated wounds was confirmed by in situ hybridization, and laser scan cytometry. A delay in the apoptosis patterns was seen in diabetic wounds compared to curcumin treated wounds as shown by terminal deoxynucleotidyl transferase-mediated deoxyuridyl triphosphate nick end labeling analysis. Curcumin was effective both orally and topically. These results show that curcumin enhanced wound repair in diabetic impaired healing, and could be developed as a pharmacological agent in such clinical settings.

  13. Chronic Oral Pelargonidin Alleviates Streptozotocin-Induced Diabetic Neuropathic Hyperalgesia in Rat: Involvement of Oxidative Stress

    PubMed Central

    Mirshekar, Mohammadali; Roghani, Mehrdad; Khalili, Mohsen; Baluchnejadmojarad, Tourandokht; Arab Moazzen, Saiedeh

    2010-01-01

    Background: Diabetes mellitus in some clinical cases is accompanied with hyperalgesia. In this study, we evaluated the possible beneficial effect of chronic pelargonidin (PG) treatment on hyperalgesia in streptozotocin (STZ)-diabetic neuropathic rat. Methods: Male Wistar rats (n = 56) were divided into seven groups, i.e. control, diabetic, PG-treated control, PG (single- and multiple-dose)-treated diabetic, and sodium salicylate-treated control and diabetics. For induction of diabetes, STZ was injected i.p. at a single dose of 60 mg/kg. PG was orally administered at a dose of 10 mg/kg once and/or on alternate days for 8 weeks; 1 week after diabetes induction. After two months, hyperalgesia was assessed using standard formalin and hot tail immersion tests. Meanwhile, markers of oxidative stress in brain were measured. One-way analysis of variance was used for statistical analysis of the data. Results: Diabetic rats showed a marked chemical and thermal hyperalgesia, indicating that development of diabetic neuropathy and PG treatment (especially multiple-doses) significantly ameliorated the alteration in hyperalg