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.

CONCLUSION:

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: Botond Literáti-Nagy, Kálmán Tory, Barna Peitl, Ágnes Bajza, László Korányi, Zsuzsanna Literáti-Nagy, Philip L Hooper, László Vígh, Zoltán Szilvássy
• Journal: Metabolic syndrome and related disorders (Metab Syndr Relat Disord) Vol. 12 Issue 2 Pg. 125-31 (Mar 2014) ISSN: 1557-8518 [Electronic] United States
• PMID: 24386957 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Hypoglycemic Agents
• Oximes
• Piperidines
• BGP 15

Topics

• Animals
• Diabetes Mellitus, Experimental (drug therapy, metabolism)
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Hypercholesterolemia (drug therapy, metabolism)
• Hypoglycemic Agents (therapeutic use)
• Insulin Resistance
• Male
• Oximes (therapeutic use)
• Piperidines (therapeutic use)
• Rabbits
• Rats
• Rats, Sprague-Dawley
• Rats, Wistar
• Vasodilation (drug effects)