scholarly journals Effect of Insulin Sensitizers and Sodium Glucose Cotransporter 2 Inhibitor on Glycemic State and Cardiovascular Performance in Type II Diabetic Rats

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
S F Ewida ◽  
A M H Shabaan ◽  
H F Eldomiaty ◽  
G S Y Hanna ◽  
S E Hassabelnabi ◽  
...  

Abstract Background Cardiovascular disease is the most life-threatening diabetic complication. Type II diabetes may lead to damage of the heart muscle. Sodium glucose cotransporter 2 (SGL2) inhibitors are a new class of diabetic medications indicated only for the treatment of type II diabetes. Aim This investigation was assigned to compare the effect of metformin and SGL2 inhibitors (dapaglifilizone) in type II diabetic rats. Design and methods: Eighty rats divided into four groups were used: non diabetic; diabetic; diabetic metformin -treated; diabetic dapagliflizoline- treated. At the end, arterial blood pressure and cardiac performance (cardiac contractility and heart rate) were assessed. Serum glucose, glycosylated hemoglobin (HbA1c), insulin, lipid profile, total antioxidant capacity, malondialdehyde, tumor necrosis factor α were measured. HOMA-IR index was calculated. DNA changes were assessed from hearts and aortea. Aortic endothelial changes recorded using H&E and masson trichome techniques. Results Glycemic index, lipid profile, oxidative stress and inflammatory parameters were significantly improved in both metformin and dapagliflizoline treated groups with also significant improvement in blood pressure, Cardiac performance and reduction in collagen deposition in aortic tissue and DNA fragmentation. Dapagliflizoline treatment results were significantly improved in all parameters compared to metformin treatment. Conclusion SGL2 inhibitors (dapaglifilizone) successfully restored glycemic state, cardiac performance, DNA and endothelial changes in type II diabetic rats compared to metformin.

2018 ◽  
Vol 4 (1) ◽  
pp. 1431474
Author(s):  
Md. Mustahsan Billah ◽  
S.M. Masud Rana ◽  
Nahida Akter ◽  
Mohammad Salim Hossain ◽  
Junxian Lim

2012 ◽  
Vol 13 (3) ◽  
pp. 334-340 ◽  
Author(s):  
Kulwinder Singh ◽  
Kuldeepak Sharma ◽  
Manjeet Singh ◽  
PL Sharma

Hypothesis: This study was designed to investigate the cardio-renal protective effect of AVE-0991, a non-peptide Mas-receptor agonist, and A-779, a Mas-receptor antagonist, in diabetic rats. Materials and methods: Wistar rats treated with streptozotocin (50 mg/kg, i.p., once), developed diabetes mellitus after 1 week. After 8 weeks, myocardial functions were assessed by measuring left ventricular developed pressure (LVDP), rate of left ventricular pressure development (d p/d tmax), rate of left ventricular pressure decay (d p/d tmin) and left ventricular end diastolic pressure (LVEDP) on an isolated Langendorff’s heart preparation. Further, mean arterial blood pressure (MABP) was measured by using the tail-cuff method. Assessment of renal functions and lipid profile was carried out using a spectrophotometer. Results: The administration of streptozotocin to rats produced persistent hyperglycaemia, dyslipidaemia and hypertension which consequently produced cardiac and renal dysfunction in 8 weeks. AVE0991 treatment produced cardio-renal protective effects, as evidenced by a significant increase in LVDP, d p/d tmax, d p/d tmin and a significant decrease in LVEDP, BUN, and protein urea. Further, AVE-0991 treatment for the first time has been shown to reduce dyslipidaemia and produced antihyperglycaemic activity in streptozotocin-treated rats. However, MABP and creatinine clearance remained unaffected with AVE-0991 treatment. Conclusions: AVE-0991 produced cardio-renal protection possibly by improving glucose and lipid metabolism in diabetic rats, independent of its blood pressure lowering action.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Christian Kuété Fofié ◽  
Elvine Pami Nguelefack-Mbuyo ◽  
Nole Tsabang ◽  
Albert Kamanyi ◽  
Télesphore Benoît Nguelefack

Parts of Ceiba pentandra are wildly used in Africa to treat diabetes and previous works have demonstrated their in vivo antidiabetic effects on type 1 diabetes models. In addition, it has been recently shown that the decoction and the methanol extract from the stem bark of C. pentandra potentiate in vitro, the peripheral glucose consumption by the liver and skeletal muscle slices. But nothing is known about its effect on type II diabetes, especially on insulin resistance condition. We investigated herein the antihyperglycemic, insulin-sensitizing potential, and cardioprotective effects of the dried decoction from the stem bark of Ceiba pentandra (DCP) in dexamethasone-induced insulin resistant rats. DCP phytochemical analysis using LC-MS showed the presence of many compounds, including 8-formyl-7-hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4-naphthaquinone, 2,4,6-trimethoxyphenol, and vavain. Wistar rats were given intramuscularly (i.m.) dexamethasone (1 mg/kg/day) alone or concomitantly with oral doses of DCP (75 or 150 mg/kg/day) or metformin (40 mg/kg/day) for 9 days. Parameters such as body weight, glycemia, oral glucose tolerance, plasma triglycerides and cholesterol, blood pressure, and heart rate were evaluated. Moreover, cardiac, hepatic and aortic antioxidants (reduced glutathione, catalase, and superoxide dismutase), malondialdehyde level, and nitric oxide content were determined. DCP decreased glycemia by up to 34% and corrected the impairment of glucose tolerance induced by dexamethasone but has no significant effect on blood pressure and heart rate. DCP reduced the total plasma cholesterol and triglycerides as compared to animals treated only with dexamethasone. DCP also increased catalase, glutathione, and NO levels impaired by dexamethasone, without any effect on SOD and malondialdehyde. In conclusion, the decoction of the stem bark of Ceiba pentandra has insulin sensitive effects as demonstrated by the improvement of glucose tolerance, oxidative status, and plasma lipid profile. This extract may therefore be a good candidate for the treatment of type II diabetes.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Claudius Balzer ◽  
Franz Baudenbacher ◽  
Michele M Salzman ◽  
William J Cleveland ◽  
Susan Eagle ◽  
...  

Patients with metabolic syndrome are at higher risk for cardiac arrest (CA), and also have worse neurologic outcome after CA related to their comorbidities (e.g., Type 2 Diabetes Mellitus [T2DM]). Using Zucker Diabetic Fatty (ZDF) rats as a new and relevant model with common comorbidities for CA and cardiopulmonary resuscitation (CPR), we hypothesized that T2DM is associated with a lower chance for return of spontaneous circulation (ROSC) and/or a worse outcome regarding heart function after asphyxial CA compared to their lean littermates. Two groups of rats (8 ZDF, 7 lean) were monitored for 37±2 weeks. The rats were anesthetized and intubated; heart rate was monitored by subcutaneous ECG needles. Femoral artery and vein were cannulated for continuous blood pressure measurement and delivery of fluids and medications, respectively. Before ventilation was stopped to initiate asphyxial CA, rocuronium was given. After 8 minutes of CA, ventilation was re-initiated with FiO 2 1.0, epinephrine and sodium-bicarbonate were administered, and pneumatic chest compression were started with 200 compressions per minute. Chest compressions were stopped when a systolic blood pressure of 120 mmHg was achieved. During 4 hours of observation, vital parameters were closely monitored, blood gases were measured, and ejection fraction (EF %) was assessed with ultrasound. Data are mean ± SD. Statistics: Unpaired student’s t-test (two-tailed), α.05. At baseline, ZDF rats showed significantly higher blood glucose levels (504±52 vs 174±14 mg/dl) compared to their lean littermates. All ZDF and lean rats achieved ROSC, and measurements taken directly after ROSC and after the first hour showed no relevant differences. After four hours, there was no difference in heart rate between ZDF and lean rats. However, diabetic rats had a significantly higher mean arterial blood pressure (142±24vs. 107±19 mmHg) and ejection fraction (42±16%vs 20±8%) compared to their lean littermates. The hypothesis that ROSC-rate in diabetic rats would be lower could not be proven. Conversely, the ZDF rats showed a significantly higher blood pressure related to an increased EF%. Further analysis in this study will focus on the impact of T2DM on cardiac and neurological ischemia-reperfusion injury.


1970 ◽  
Vol 11 (1) ◽  
pp. 33-38 ◽  
Author(s):  
Ashok Sahu ◽  
Trapti Gupta ◽  
Arvind Kavishwar ◽  
Purnima Dey Sarkar ◽  
RK Singh

Cardiovascular disease is the most frequent cause of death in patient with diabetes. It is difficult to evaluate cardiovascular status of patients with diabetes because of complex symptomatology. NTproBNP, a split peptide from pro BNP molecule is a novel biomarker, released from cardiac myocytes in response to myocardial stretch, cardio vascular disease, endothelial dysfunction and heart failure. We aimed to test that is elevated NTproBNP levels associated with increased risk of cardiovascular disease in diabetes patients in comparison to matched control. Demographic, anthropometric measure, NT pro BNP, lipid profile, blood glucose were estimated and compared among angiographically proven cardiovascular disease patients with diabetes and healthy controls. Univariate and multivariate analysis were carried out to compare individual factor using t-Test, ANOVA and the inter group comparisons were done by using Bon ferroni Post Hoc test. Patients with type 2 diabetes were shown to have higher NTproBNP values (n=50, 1481.021±813.405) than control subjects (n=50, 23.562±23.395) (p <0.05). NTproBNP levels were independently related to diabetes after adjustment for age, sex, family history, smoking, obesity, blood pressure and lipid profile. Our data suggests that the secretion of NT pro BNP is increased in type II diabetes patients, suggesting association of diabetes and NTproBNP in cardio vascular disease with higher prevalence. Thus NTproBNP may serve as a screening tool to diagnose patients with type II diabetes with cardiovascular disease having complex symptomatology. Keyword: NTproBNP, Cardiovascular disease, Diabetes DOI:10.3329/jom.v11i1.4266 J Medicine 2010: 11: 33-38


2004 ◽  
Vol 82 (10) ◽  
pp. 888-894 ◽  
Author(s):  
Tod A Clark ◽  
Andrea L Edel ◽  
Clayton E Heyliger ◽  
Grant N Pierce

A novel black tea decoction containing vanadate has successfully replaced insulin in a rat model of insulin-dependent diabetes but is untested in non-insulin-dependent diabetic animals. A tea-vanadate decoction (TV) containing 30 or 40 mg sodium orthovanadate was administered by oral gavage to two groups of Zucker diabetic fatty rats and a conventional water vehicle containing 30 or 40 mg of sodium orthovanadate to two others. In the latter group receiving the 30-mg dose, vanadate induced diarrhea in 50% of the rats and death in 10%. In contrast, TV-treated rats had no incidence of diarrhea and no deaths. Symptoms were more severe in both groups with higher vanadate doses, so these were discontinued. After ~16 weeks, the level of vanadium in plasma and tissue extracts was negligible in a further group of untreated rats but highly elevated after vanadate treatment. Vanadium levels were not significantly different between the TV-treated diabetic rats and the diabetic rats given vanadate in a water vehicle. Over the 115 days of the study, blood glucose levels increased from ~17 to 25 mmol/L in untreated diabetic rats. This was effectively lowered (to <10 mmol/L) by TV treatment. Fasting blood glucose levels were 5, 7, and 20 mmol/L in control (nondiabetic, untreated), TV-treated and untreated diabetic rats, respectively. Rats required treatment with TV for only ~50% of the days in the study. Increase in body mass during the study was significantly lower in untreated diabetic rats (despite higher food intake) than the other groups. Body mass gain and food intake were normal in TV-treated rats. Water intake was 28 mL/rat daily in control rats, 130 mL/rat daily in untreated diabetic rats, and 52 mL/rat daily in TV-treated diabetic rats. Plasma creatinine and aspartate aminotransferase levels were significantly depressed in untreated diabetic rats, and TV treatment normalized this. Our results demonstrate that a novel oral therapy containing black tea and vanadate possesses a striking capacity to regulate glucose and attenuates complications in a rat model of type II diabetes. Key words: diabetes mellitus, tea, glycemia, type II diabetes.


Sign in / Sign up

Export Citation Format

Share Document