title: The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats.
abstract: OBJECTIVE
  To investigate the effects of pioglitazone and metformin treatment during pre-diabetic period for the prevention of diabetes in a rat model.
  
  
  METHODS
  OLETF rats aged 18-weeks, were treated with pioglitazone (10 mg/kg/day) and metformin (300 mg/kg/day) for 10 weeks from their pre-diabetic period. We measured weight, lipid profiles, fat distribution, glucose tolerance, and pancreatic insulin content.
  
  
  RESULTS
  Prominent weight gain (mostly subcutaneous fat area) was observed in the pioglitazone-treated OLETF (O-P) rats versus significant weight loss was observed in the metformin-treated OLETF (O-M) rats. Pioglitazone reversed the serum triglyceride (TG) and FFAs levels to normal (TG 0.46 +/- 0.04 vs 0.88 +/- 0.05 mmol/l in LETO). At the age of 28 weeks, the O-P rats showed completely normal glucose tolerance, and the glucose disposal rate (GDR) was markedly improved (25.6 +/- 0.4 vs 20.6 +/- 0.5 mg/min/kg in O-C, p < 0.05). The O-M rats also showed an improved fasting glucose and GDR level, but not as much as those with O-P rats. The pancreas insulin contents were much improved in the O-P rats (22.9 +/- 1.2 vs 18.8 +/- 1.3 nmol/pancreas in O-M rats, p < 0.05) with histological improvement.
  
  
  CONCLUSIONS
  The pre-diabetic treatment with pioglitazone, despite significant weight gain, completely prevents to develop diabetes and enhances beta cell function with preservation of islet cell changes. Metformin treatment was also effective, but mainly by ameliorating the insulin resistance with marked reduction in body weight. The reversal of dyslipidaemia and the fat redistribution might contribute to the greater improvement of pioglitazone treatment compared to metformin in OLETF rats.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Bundang Hospital, Seongnam, Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Choi
authors.forename: Zheng Shan
authors.initials: ZS
authors.lastname: Zhao
authors.forename: Yong Jik
authors.initials: YJ
authors.lastname: Lee
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Kim
authors.forename: Dae Jung
authors.initials: DJ
authors.lastname: Kim
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Ahn
authors.forename: Sung Kil
authors.initials: SK
authors.lastname: Lim
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Cha
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D000077205:Pioglitazone; D011236:Prediabetic State / Q000188:drug therapy; D051381:Rats; D020334:Rats, Inbred OLETF; D045162:Thiazolidinediones / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D008687:Metformin; D000077205:Pioglitazone