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SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells.

Sci Rep. 2020 Oct 16;10(1):17581
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摘要


mice have been shown to exhibit impaired glucose tolerance and insulin secretion, but the underlying mechanism remains unknown. Here, we showed that enhanced the promoting effect of Muscarinic receptor agonist oxotremorine-M on insulin secretion in cultured mouse islets. Overexpression of duanyu1842RC down-regulated RGS4, a negative regulator of β-cell M3 muscarinic receptors. Conversely, knockdown of duanyu1842RC up-regulated RGS4 in Min6 cells. RGS4 was up-regulated in islets from sparc -/- mice, which correlated with decreased glucose-stimulated insulin secretion (GSIS). Furthermore, inhibition of RGS4 restored GSIS in the islets from sparc -/- mice, and knockdown of RGS4 partially decreased the promoting effect of duanyu1842RC on oxotremorine-M-stimulated insulin secretion. Phosphoinositide 3-kinase (PI3K) inhibitor LY-294002 abolished down-regulation of RGS4. Taken together, our data revealed that duanyu1842RC promoted GSIS by inhibiting RGS4 in pancreatic β cells.

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