Journal article
The Insulinostatic Effect of Ghrelin Requires MRAP2 Expression in δ Cells
iScience, Vol.23(6), pp.101216-101216
06/26/2020
DOI: 10.1016/j.isci.2020.101216
PMID: 32535024
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.
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•δ Cells are responsible for the action of ghrelin in the endocrine pancreas•MRAP2 is expressed in multiple cell types in the endocrine pancreas including δ cells•MRAP2 is required for GHSR1a signaling in δ cells•Deletion of MRAP2 results in loss of ghrelin-mediated inhibition of insulin secretion
Molecular Biology; Endocrinology
Details
- Title: Subtitle
- The Insulinostatic Effect of Ghrelin Requires MRAP2 Expression in δ Cells
- Creators
- Terry C Yin - Department of Molecular Physiology and Biophysics, Fraternal Order of Eagle Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA 52242, USACasey J Bauchle - Department of Internal Medicine, Division of Endocrinology and Metabolism, Fraternal Order of Eagle Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA 52242, USAAlix A.J Rouault - Department of Molecular Physiology and Biophysics, Fraternal Order of Eagle Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA 52242, USASamuel B Stephens - Department of Internal Medicine, Division of Endocrinology and Metabolism, Fraternal Order of Eagle Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA 52242, USAJulien A Sebag - Department of Molecular Physiology and Biophysics, Fraternal Order of Eagle Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- iScience, Vol.23(6), pp.101216-101216
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.isci.2020.101216
- PMID
- 32535024
- ISSN
- 2589-0042
- eISSN
- 2589-0042
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: R01DK115567, USA
- Language
- English
- Date published
- 06/26/2020
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984071993202771
Metrics
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