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Improvement of insulin sensitivity by a novel drug candidate, BGP-15, in different animal studies.
Literáti-Nagy, Botond; Tory, Kálmán; Peitl, Barna; Bajza, Ágnes; Korányi, László; Literáti-Nagy, Zsuzsanna; Hooper, Philip L; Vígh, László; Szilvássy, Zoltán.
Afiliación
  • Literáti-Nagy B; 1 Drug Research Center Ltd. , Balatonfüred, Hungary .
Metab Syndr Relat Disord ; 12(2): 125-31, 2014 Mar.
Article en En | MEDLINE | ID: mdl-24386957
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oximas / Piperidinas / Resistencia a la Insulina / Diabetes Mellitus Experimental / Hipoglucemiantes Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Metab Syndr Relat Disord Asunto de la revista: METABOLISMO Año: 2014 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oximas / Piperidinas / Resistencia a la Insulina / Diabetes Mellitus Experimental / Hipoglucemiantes Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Metab Syndr Relat Disord Asunto de la revista: METABOLISMO Año: 2014 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Estados Unidos