Intraislet glucagon signaling is critical for maintaining glucose homeostasis

• DOI: 10.1172/jci.insight.127994
• Publication Date: 2019-04-23T16:01:00Z
• Authors: Lu Zhu; Diptadip Dattaroy; Jonathan Pham; Lingdi Wang; Luiz F. Barella; Yinghong Cui; Kenneth J. Wilkins; Bryan L. Roth; Ute Hochgeschwender; Franz M. Matschinsky; Klaus H. Kaestner; Nicolai M. Doliba; Jürgen Wess
• Keywords: Homeostasis; Alpha cell

Glucagon, a hormone released from pancreatic α cells, plays key role in maintaining proper glucose homeostasis and has been implicated the pathophysiology of diabetes. In vitro studies suggest that intraislet glucagon can modulate function β cells. However, because lack suitable experimental tools, vivo physiological this cross-talk remained elusive. To address issue, we generated mouse model selectively expressed an inhibitory designer GPCR (Gi DREADD) cells only. Drug-induced activation receptor almost completely shut off secretion vivo, resulting markedly impaired insulin secretion, hyperglycemia, intolerance. Additional with human islets indicated stimulates release primarily by activating cell GLP-1 receptors. These findings strongly signaling is essential for vivo. Our work may pave way toward development novel classes antidiabetic drugs act modulating between