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Mechanistic Investigation of GHS-R Mediated Glucose-Stimulated Insulin Secretion in Pancreatic Islets.
- Source :
- Biomolecules (2218-273X); Mar2022, Vol. 12 Issue 3, p407, 17p
- Publication Year :
- 2022
-
Abstract
- Ghrelin receptor, a growth hormone secretagogue receptor (GHS-R), is expressed in the pancreas. Emerging evidence indicates that GHS-R is involved in the regulation of glucose-stimulated insulin secretion (GSIS), but the mechanism by which GHS-R regulates GSIS in the pancreas is unclear. In this study, we investigated the role of GHS-R on GSIS in detail using global Ghsr<superscript>−/−</superscript> mice (in vivo) and Ghsr-ablated pancreatic islets (ex vivo). GSIS was attenuated in both Ghsr<superscript>−/−</superscript> mice and Ghsr-ablated islets, while the islet morphology was similar between WT and Ghsr<superscript>−/−</superscript> mice. To elucidate the mechanism underpinning Ghsr-mediated GSIS, we investigated the key steps of the GSIS signaling cascade. The gene expression of glucose transporter 2 (Glut2) and the glucose-metabolic intermediate—glucose-6-phosphate (G6P) were reduced in Ghsr-ablated islets, supporting decreased glucose uptake. There was no difference in mitochondrial DNA content in the islets of WT and Ghsr<superscript>−/−</superscript> mice, but the ATP/ADP ratio in Ghsr<superscript>−/−</superscript> islets was significantly lower than that of WT islets. Moreover, the expression of pancreatic and duodenal homeobox 1 (Pdx1), as well as insulin signaling genes of insulin receptor (IR) and insulin receptor substrates 1 and 2 (IRS1/IRS2), was downregulated in Ghsr<superscript>−/−</superscript> islets. Akt is the key mediator of the insulin signaling cascade. Concurrently, Akt phosphorylation was reduced in the pancreas of Ghsr<superscript>−/−</superscript> mice under both insulin-stimulated and homeostatic conditions. These findings demonstrate that GHS-R ablation affects key components of the insulin signaling pathway in the pancreas, suggesting the existence of a cross-talk between GHS-R and the insulin signaling pathway in pancreatic islets, and GHS-R likely regulates GSIS via the Akt-Pdx1-GLUT2 pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2218273X
- Volume :
- 12
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Biomolecules (2218-273X)
- Publication Type :
- Academic Journal
- Accession number :
- 155980803
- Full Text :
- https://doi.org/10.3390/biom12030407