title: Nitrite increases glucose-stimulated insulin secretion and islet insulin content in obese type 2 diabetic male rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Neurophysiology Research Center and Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Sevda
authors.initials: S
authors.lastname: Gheibi
authors.affiliation: Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Bakhtiarzadeh
authors.affiliation: Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Sajad
authors.initials: S
authors.lastname: Jeddi
authors.affiliation: Atherosclerosis and Coronary Artery Research Center, Department of Physiology, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran.
authors.forename: Khadijeh
authors.initials: K
authors.lastname: Farrokhfall
authors.affiliation: Neurophysiology Research Center and Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Homeira
authors.initials: H
authors.lastname: Zardooz
authors.affiliation: Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Ghasemi@endocrine.ac.ir.
authors.forename: Asghar
authors.initials: A
authors.lastname: Ghasemi
mesh_terms: D000818:Animals; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004435:Eating; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D009573:Nitrites; D009569:Nitric Oxide; D005947:Glucose
keywords: Glucose tolerance; Inflammation; Insulin resistance; Insulin secretion; Nitrite; Type 2 diabetes