Endocrine Abstracts

Introduction: Type 2 diabetes is associated with impaired nitric oxide (NO) bioavailability; nitrate administration might act as a potential therapeutic agent in diabetes through nitrate/nitrite/NO pathway. The aim of this study was to determine the effects of sodium nitrate on glucose tolerance, insulin sensitivity, inflammation, glucose-stimulated insulin secretion (GSIS), and islet insulin content in obese type 2 diabetic male rats.

Methods: Male Wistar rats were divided into four groups: Control, control+nitrate, diabetes, and diabetes+nitrate. Diabetes was induced using high-fat diet and low-dose of streptozotocin. Sodium nitrate (100 mg/l in drinking water) was administered for 2 months. Serum levels of fasting glucose, insulin, and lipid profile were measured and the insulin resistance/sensitivity indices were calculated every 2-weeks. At the end of the study, tissue levels of glucose transporter 4 (GLUT4) protein and serum interleukin-1 beta (IL-1β) were measured as well as glucose and insulin tolerance test were done. GSIS from isolated pancreatic islets and islet insulin content were also determined.

Results: Compared to the control group, diabetic rats had glucose intolerance, dyslipidemia, and higher serum glucose and insulin. In diabetic rats, nitrate significantly improved glucose (area under the curve: 26603 vs. 31947, P<0.001) and insulin (area under the curve: 6981 vs 8968, P<0.001) tolerance, insulin resistance, insulin sensitivity, lipid profile, and decreased fasting glucose (8%) and insulin (11%), but had no effect on GSIS and islet insulin content. In diabetic rats, nitrate significantly increased tissue levels of GLUT4 by 17% and 22% in soleus muscle and epididymal adipose tissue, respectively. Nitrate also decreased elevated serum IL-1β in diabetic rats (4.7±0.5 vs. 3.2±0.6 pg/ml, P=0.02).

Conclusion: Nitrate administration had favourable effects on glucose tolerance, insulin resistance, insulin sensitivity, inflammation, and dyslipidemia in type 2 diabetic rats.

Keywords: Glucose tolerance; Insulin resistance; Insulin sensitivity; Inflammation; Sodium nitrate; Type 2 diabetes.