The Insulinostatic Effect of Ghrelin Requires MRAP2 Expression in δ Cells

IScience
Terry C YinJulien A Sebag

Abstract

Ghrelin regulates both energy intake and glucose homeostasis. In the endocrine pancreas, ghrelin inhibits insulin release to prevent hypoglycemia during fasting. The mechanism through which this is accomplished is unclear, but recent studies suggest that ghrelin acts on δ cells to stimulate somatostatin release, which in turn inhibits insulin release from β cells. Recently, the Melanocortin Receptor Accessory Protein 2 (MRAP2) was identified as an essential partner of the ghrelin receptor (GHSR1a) in mediating the central orexigenic action of ghrelin. In this study we show that MRAP2 is expressed in islet δ cells and is required for ghrelin to elicit a calcium response in those cells. Additionally, we show that both global and δ cell targeted deletion of MRAP2 abrogates the insulinostatic effect of ghrelin. Together, these findings establish that ghrelin signaling within δ cells is essential for the inhibition of insulin release and identify MRAP2 as a regulator of insulin secretion.

Citations

May 1, 2021·International Journal of Molecular Sciences·Geetali PradhanYuxiang Sun
Dec 22, 2021·Journal of Neuroendocrinology·Mitchell Ty RinguetSebastian George Barton Furness

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