RT Journal Article
SR Electronic
T1 SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β-cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.11.902916
DO 10.1101/2020.01.11.902916
A1 Li Hu
A1 Fengli He
A1 Meifeng Huang
A1 Qian Zhao
A1 Lamei Cheng
A1 Neveen Said
A1 Zhiguang Zhou
A1 Feng Liu
A1 Yan-Shan Dai
YR 2020
UL http://biorxiv.org/content/early/2020/01/13/2020.01.11.902916.abstract
AB SPARC-deficient mice have been shown to exhibit impaired glucose tolerance and insulin secretion, but the underlying mechanism remains unknown. Here, we show that SPARC enhanced the promoting effect of Muscarinic receptor agonist oxotremorine-M on insulin secretion in cultured mouse islets. Overexpression of SPARC down-regulated RGS4, a negative regulator of β-cell M3 muscarinic receptors. Conversely, knockdown of SPARC 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 sparc -/- mice, and knockdown of RGS4 partially decreased the promoting effect of SPARC on oxotremorine-M stimulated insulin secretion. Phosphoinositide 3-kinase (PI3K) inhibitor LY-294002 abolished SPARC-induced down-regulation of RGS4. Taken together, our data revealed that SPARC promoted GSIS by inhibiting RGS4 in pancreatic β cells.