| First Author | Liu L | Year | 2021 |
| Journal | JCI Insight | Volume | 6 |
| Issue | 24 | PubMed ID | 34752420 |
| Mgi Jnum | J:320958 | Mgi Id | MGI:6861321 |
| Doi | 10.1172/jci.insight.152852 | Citation | Liu L, et al. (2021) Gq signaling in alpha cells is critical for maintaining euglycemia. JCI Insight 6(24):e152852 |
| abstractText | Glucagon, a hormone released from pancreatic alpha cells, plays a key role in maintaining euglycemia. New insights into the signaling pathways that control glucagon secretion may stimulate the development of novel therapeutic agents. In this study, we investigated the potential regulation of alpha cell function by G proteins of the Gq family. The use of a chemogenetic strategy allowed us to selectively activate Gq signaling in mouse alpha cells in vitro and in vivo. Acute stimulation of alpha cell Gq signaling led to elevated plasma glucagon levels, accompanied by increased insulin release and improved glucose tolerance. Moreover, chronic activation of this pathway greatly improved glucose tolerance in obese mice. We also identified an endogenous Gq-coupled receptor (vasopressin 1b receptor; V1bR) that was enriched in mouse and human alpha cells. Agonist-induced activation of the V1bR strongly stimulated glucagon release in a Gq-dependent fashion. In vivo studies indicated that V1bR-mediated glucagon release played a key role in the counterregulatory hyperglucagonemia under hypoglycemic and glucopenic conditions. These data indicate that alpha cell Gq signaling represents an important regulator of glucagon secretion, resulting in multiple beneficial metabolic effects. Thus, drugs that target alpha cell-enriched Gq-coupled receptors may prove useful to restore euglycemia in various pathophysiological conditions. |
