title: Vildagliptin selectively ameliorates GLP-1, GLUT4, SREBP-1c mRNA levels and stimulates β-cell proliferation resulting in improved glucose homeostasis in rats with streptozotocin-induced diabetes.
abstract: OBJECTIVE
  Inhibitors of dipeptidyl peptidase-4 (DPP-4), a key regulator of the actions of incretin hormones, exert antihyperglycemic effects in type 2 diabetic patients. A major unanswered question concerns the potential ability of DPP-4 inhibition to have beneficial disease-modifying effects, specifically to attenuate loss of pancreatic β-cell mass and function due to oxidative stress induced inflammation. Here, we investigated the effects of a potent and selective DPP-4 inhibitor vildagliptin on glycemic control, pancreatic β-cell mass and function, genes and proteins expressions, tumor necrosis factor-alpha, and nitric oxide in an n2-STZ diabetic model of rat with defects in insulin sensitivity and secretion.
  
  
  METHODS
  To induce NIDDM, STZ (sigma chemicals, USA) (90 mg/kg) was administered i.p. to a group of 2 days old pups. Another group of pups received only saline. The pups were weaned for 21 days, and 6 weeks after the injection of STZ, the animals were checked for fasting glucose level (FPG) ≥160 mg/dl were considered as diabetic.
  
  
  RESULTS
  Significant and dose-dependent correction of postprandial and fasting hyperglycemia was observed in diabetic rats following 8 weeks of chronic therapy. Treatment with vildagliptin showed increase in the number of insulin-positive β-cells in islets and improved the expressions of genes and proteins are responsible for insulin secretions. In addition, treatment of rats with vildagliptin significantly increased insulin content; and decreased the nitric oxide and TNF-alpha concentration.
  
  
  CONCLUSIONS
  These findings suggest that DPP-4 inhibitors may offer long-lasting efficacy in the treatment of diabetes mellitus by modifying the courses of the disease.
authors.affiliation: Delhi Institute of Pharmaceutical Sciences and Research, Pushp Vihar, Sector-3, MB Road, New Delhi -110017, India. atul_akarte123@rediffmail.com
authors.forename: Atul Sureshrao
authors.initials: AS
authors.lastname: Akarte
authors.forename: B P
authors.initials: BP
authors.lastname: Srinivasan
authors.forename: Sonia
authors.initials: S
authors.lastname: Gandhi
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D013311:Streptozocin / Q000009:adverse effects; D016896:Treatment Outcome; D000077597:Vildagliptin
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D051275:Glucose Transporter Type 4; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D013311:Streptozocin; D052216:Glucagon-Like Peptide 1; D000077597:Vildagliptin; D005947:Glucose; D000218:Adamantane