title: Synergic insulin sensitizing effect of rimonabant and BGP-15 in Zucker-obese rats.
abstract: Abdominal obesity is referred for as a common pathogenic root of multiple risk factors, which include insulin resistance, dyslipidemia, hypertension, and a pro-atherogenic and pro-inflammatory state. Irrespective of its psychiatric side effects, rimonabant through blocking cannabinoid-1 receptor (CB1R) induces an increase in whole body insulin sensitivity. The aim of this work was to study the effect of selected doses of another insulin sensitizer compound BGP-15, and rimonabant on insulin resistance in Zucker obese rats with a promise of inducing insulin sensitization together at lower doses than would have been expected by rimonabant alone. We found that BGP-15 potentiates the insulin sensitizing effect of rimonabant. The combination at doses, which do not induce insulin sensitization by themselves, improved insulin signaling. Furthermore our results suggest that capsaicin-induced signal may play a role in insulin sensitizing effect of both molecules. Our data might indicate that a lower dose of rimonabant in the treatment of insulin resistance and type 2 diabetes is sufficient to administer, thus a lower incidence of the unfavorable psychiatric side effects of rimonabant are to be expected.
authors: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
authors: Zsuzsanna
authors: Z
authors: Literati-Nagy
authors: Kálmán
authors: K
authors: Tory
authors: Botond
authors: B
authors: Literáti-Nagy
authors: Agnes
authors: A
authors: Bajza
authors: László
authors: L
authors: Vígh
authors: László
authors: L
authors: Vígh
authors: József
authors: J
authors: Mandl
authors: Zoltán
authors: Z
authors: Szilvássy
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004195:Disease Models, Animal; D004357:Drug Synergism; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism / Q000188:drug therapy / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D010091:Oximes / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D000077285:Rimonabant
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010091:Oximes; D010880:Piperidines; D011720:Pyrazoles; D005947:Glucose; C405586:BGP 15; D000077285:Rimonabant
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