The CB-1 Receptor Antagonist Rimonabant Modulates the Interaction Between Adipocytes and Pancreatic Beta-Cells in Vitro

Abstract

Our data show that rimonabant modulates the adipocyte - beta-cell interaction with respect to beta-cell proliferation and indicate that signalling molecules other than adiponectin and components of the Wnt pathway mediate this cross-talk.

The cannabinoid ligands SR141716A and AM251 enhance human and mouse islet function via GPR55-independent signalling

“…The effects of SR141716A on insulin secretion in vitro and in vivo in rodents have been a point of controversy in the literature. Thus, it is reported to decrease insulin hypersecretion in islets isolated from diabetic rats [36] and glucose-induced insulin secretion from mouse islets [37], but another study showed that SR141716A did not significantly affect insulin secretion from mouse islets [38]. Conversely, SR141716A was found to reversibly stimulate insulin secretion from human islets [39], and its chronic administration improved islet function and morphology in diabetic rats [40].…”

Obesity and Diabetes

“…Thus, leptin-and rimonabantcaused inhibition of AMPK may result in the observed synergistic effects on food intake (Boustany-Kari et al 2011). In addition, rimonabant increases the expression of adiponectin by adipocytes (Bensaid et al 2003;Despres et al 2005), and this is supposed to be one reason for the improved insulin sensitivity with rimonabant observed in vivo ( € Ulgen et al 2011). Inhibition of peripheral CB1 receptors in adipocytes directly promotes transdifferentiation of white adipocytes into a mitochondria-rich, thermogenic brown fat phenotype, resulting in enhanced thermogenesis and insulin sensitivity (Perwitz et al 2010).…”