β Cell tone is defined by proglucagon peptides through cAMP signaling.

Autor:	Capozzi ME; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA., Svendsen B; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA., Encisco SE; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA., Lewandowski SL; Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Wisconsin-Madison, Madison, Wisconsin, USA., Martin MD; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA., Lin H; Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Alberta, Canada., Jaffe JL; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA., Coch RW; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.; Department of Medicine and., Haldeman JM; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.; Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA., MacDonald PE; Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Alberta, Canada., Merrins MJ; Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Wisconsin-Madison, Madison, Wisconsin, USA., D'Alessio DA; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.; Department of Medicine and., Campbell JE; Duke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.; Department of Medicine and.; Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2019 Mar 07; Vol. 4 (5). Date of Electronic Publication: 2019 Mar 07 (Print Publication: 2019).
DOI:	10.1172/jci.insight.126742
Abstrakt:	Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis. Here, we demonstrate the importance of proglucagon-derived peptides (PGDPs) for α to β cell communication and control of insulin secretion. Signaling through this system occurs through both the glucagon-like peptide receptor (Glp1r) and glucagon receptor (Gcgr). Loss of PGDPs, or blockade of their receptors, decreases insulin secretion in response to both metabolic and nonmetabolic stimulation of mouse and human islets. This effect is due to reduced β cell cAMP and affects the quantity but not dynamics of insulin release, indicating that PGDPs dictate the magnitude of insulin output in an isolated islet. In healthy mice, additional factors that stimulate cAMP can compensate for loss of PGDP signaling; however, input from α cells is essential to maintain glucose tolerance during the metabolic stress induced by high-fat feeding. These findings demonstrate an essential role for α cell regulation of β cells, raising the possibility that abnormal paracrine signaling contributes to impaired insulin secretion in diabetes. Moreover, these findings support reconsideration of the role for α cells in postprandial glucose control.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu