Augmented glucose-induced insulin release in mice lacking G(o2), but not G(o1) or G(i) proteins

作者：Wang Ying; Park Sangeun; Bajpayee Neil S; Nagaoka Yoshiko; Boulay Guylain; Birnbaumer Lutz^*; Jiang Meisheng

来源：Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(4): 1693-1698.

DOI：10.1073/pnas.1018903108

• somatostatin
• exocytosis
• islet activating protein
• signal transduction
• G-protein-coupled receptor

Insulin secretion by pancreatic beta cells is a complex and highly regulated process. Disruption of this process can lead to diabetes mellitus. One of the various pathways involved in the regulation of insulin secretion is the activation of heterotrimeric G proteins. Bordetella pertussis toxin (PTX) promotes insulin secretion, suggesting the involvement of one or more of three G(i) and/or two Go proteins as suppressors of insulin secretion from beta cells. However, neither the mechanism of this inhibitory modulation of insulin secretion nor the identity of the G(i/o) proteins involved has been elucidated. Here we show that one of the two splice variants of G(o), G(o2), is a key player in the control of glucose-induced insulin secretion by beta cells. Mice lacking G(o2)alpha, but not those lacking a subunits of either G(o1) or any G(i) proteins, handle glucose loads more efficiently than wild-type (WT) mice, and do so by increased glucose-induced insulin secretion. We thus provide unique genetic evidence that the G(o2) protein is a transducer in an inhibitory pathway that prevents damaging oversecretion of insulin.

• 出版日期2011-1-25
• 单位NIH