title: Improvement of insulin sensitivity by a novel drug candidate, BGP-15, in different animal studies.
abstract: BACKGROUND
  Insulin resistance has been recognized as the most significant predictor of further development of type 2 diabetes mellitus (T2DM). Here we investigated the effect of a heat shock protein (HSP) co-inducer, BGP-15, on insulin sensitivity in different insulin-resistant animal models and compared its effect with insulin secretagogues and insulin sensitizers.
  
  
  METHODS
  Insulin sensitivity was assessed by the hyperinsulinemic euglycemic glucose clamp technique in normal and cholesterol-fed rabbits and in healthy Wistar and Goto-Kakizaki (GK) rats in dose-ranging studies. We also examined the effect of BGP-15 on streptozotocin-induced changes in the vasorelaxation of the aorta in Sprague-Dawley rats.
  
  
  RESULTS
  BGP-15 doses of 10 and 30 mg/kg increased insulin sensitivity by 50% and 70%, respectively, in cholesterol-fed but not in normal rabbits. After 5 days of treatment with BGP-15, the glucose infusion rate was increased in a dose-dependent manner in genetically insulin-resistant GK rats. The most effective dose was 20 mg/kg, which showed a 71% increase in insulin sensitivity compared to control group. Administration of BGP-15 protected against streptozotocin-induced changes in vasorelaxation, which was similar to the effect of rosiglitazone.
  
  
  CONCLUSIONS
  Our results indicate that the insulin-sensitizing effect of BGP-15 is comparable to conventional insulin sensitizers. This might be of clinical utility in the treatment of T2DM.
authors.affiliation: 1 Drug Research Center Ltd. , Balatonfüred, Hungary .
authors.forename: Botond
authors.initials: B
authors.lastname: Literáti-Nagy
authors.forename: Kálmán
authors.initials: K
authors.lastname: Tory
authors.forename: Barna
authors.initials: B
authors.lastname: Peitl
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Bajza
authors.forename: László
authors.initials: L
authors.lastname: Korányi
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Literáti-Nagy
authors.forename: Philip L
authors.initials: PL
authors.lastname: Hooper
authors.forename: László
authors.initials: L
authors.lastname: Vígh
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szilvássy
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D010091:Oximes / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D010091:Oximes; D010880:Piperidines; C405586:BGP 15