Gq signaling in α cells is critical for maintaining euglycemia

• DOI: 10.1172/jci.insight.152852
• Publication Date: 2021-11-17T15:38:07Z
• Authors: Liu Liu; Diptadip Dattaroy; Katherine F. Simpson; Luiz F. Barella; Yinghong Cui; Yan Xiong; Jian Jin; Gabriele M. König; Evi Kostenis; Jefferey C. Roman; Klaus H. Kaestner; Nicolai M. Doliba; Jürgen Wess
• Keywords: Hyperglucagonemia; Glucagon receptor

Glucagon, a hormone released from pancreatic α cells, plays key role in maintaining euglycemia. New insights into the signaling pathways that control glucagon secretion may stimulate development of novel therapeutic agents. In this study, we investigated potential regulation cell function by G proteins Gq family. The use chemogenetic strategy allowed us to selectively activate mouse cells vitro and vivo. Acute stimulation led elevated plasma levels, accompanied increased insulin release improved glucose tolerance. Moreover, chronic activation pathway greatly tolerance obese mice. We also identified an endogenous Gq-coupled receptor (vasopressin 1b receptor; V1bR) was enriched human cells. Agonist-induced V1bR strongly stimulated Gq-dependent fashion. vivo studies indicated V1bR-mediated played counterregulatory hyperglucagonemia under hypoglycemic glucopenic conditions. These data indicate represents important regulator secretion, resulting multiple beneficial metabolic effects. Thus, drugs target cell–enriched receptors prove useful restore euglycemia various pathophysiological