Nitrite increases glucose-stimulated insulin secretion and islet insulin content in obese type 2 diabetic male rats

Nitric Oxide. 2017 Apr 1;64:39-51. doi: 10.1016/j.niox.2017.01.003. Epub 2017 Jan 9.


Purpose: Reduced bioavailability of nitric oxide (NO) is associated with pathogenesis of type 2 diabetes. Nitrite can act as a substrate for generation of systemic NO. The aim of this study was to examine the effects of nitrite administration on glucose-stimulated insulin secretion (GSIS) and islet insulin content in obese type 2 diabetic rats.

Methods: Male rats were divided into 4 groups: Control, control + nitrite, diabetes, and diabetes + nitrite. Sodium nitrite (50 mg/L in drinking water) was administered for 8 weeks. Diabetes was induced using high-fat diet and low-dose of streptozotocine. Serum levels of fasting glucose, insulin, and lipid profile were measured and the insulin resistance/sensitivity indices were calculated every 2 weeks. Glycated hemoglobin (HbA1C) was measured every month. 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: Nitrite administration significantly increased insulin secretion in both control and diabetic rats in presence of 16.7 mM glucose. Nitrite also significantly increased islet insulin content by 27% and 39% in both control and diabetic rats, respectively. Nitrite decreased elevated serum IL-1β in diabetic rats (4.0 ± 0.2 vs. 2.9 ± 0.2 pg/mL, P = 0.001). In diabetic rats, nitrite also significantly increased tissue levels of GLUT4 by 22% and 26% in soleus muscle and epididymal adipose tissue, respectively. In addition, nitrite significantly improved glucose and insulin tolerance, insulin sensitivity, lipid profile, and decreased fasting glucose and insulin, but had no effect on HbA1C.

Conclusions: Long-term nitrite administration increased both insulin secretion and insulin content in obese type 2 diabetic rats. In addition, nitrite therapy had favorable effects on glucose tolerance, insulin resistance, inflammation, and dyslipidemia in type 2 diabetic rats.

Keywords: Glucose tolerance; Inflammation; Insulin resistance; Insulin secretion; Nitrite; Type 2 diabetes.

MeSH terms

  • Animals
  • Body Weight
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Eating
  • Glucose / metabolism*
  • Insulin / metabolism*
  • Insulin Resistance
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Male
  • Nitric Oxide / metabolism
  • Nitrites / administration & dosage
  • Nitrites / pharmacology*
  • Rats
  • Rats, Wistar


  • Insulin
  • Nitrites
  • Nitric Oxide
  • Glucose