Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
Pathol Oncol Res. 2013 Jul;19(3):571-5. doi: 10.1007/s12253-013-9620-6. Epub 2013 May 3.
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.
腹部肥胖被认为是多种危险因素的共同致病根源，这些危险因素包括胰岛素抵抗、血脂异常、高血压以及动脉粥样硬化和炎症前状态。尽管利莫那班具有精神副作用，但通过阻断大麻素受体 1（CB1R），它会引起全身胰岛素敏感性增加。本工作的目的是研究另一种胰岛素增敏化合物 BGP-15 和利莫那班对肥胖 Zucker 大鼠胰岛素抵抗的影响，以期在低于单独使用利莫那班预期的剂量下共同诱导胰岛素敏感性。我们发现，BGP-15 增强了利莫那班的胰岛素增敏作用。在不单独引起胰岛素增敏的剂量下，联合用药改善了胰岛素信号。此外，我们的结果表明，辣椒素诱导的信号可能在这两种分子的胰岛素增敏作用中发挥作用。我们的数据可能表明，在治疗胰岛素抵抗和 2 型糖尿病时，利莫那班的低剂量足以给药，因此预计利莫那班不利的精神副作用的发生率会更低。
