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肌生成抑制蛋白相关因子 X 通过下调胰岛 β 细胞中 RGS4 蛋白促进胰岛素分泌。

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

机构信息

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Sci Rep. 2020 Oct 16;10(1):17581. doi: 10.1038/s41598-020-74593-w.

DOI:10.1038/s41598-020-74593-w
PMID:33067534
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7567887/
Abstract

SPARC-deficient mice have been shown to exhibit impaired glucose tolerance and insulin secretion, but the underlying mechanism remains unknown. Here, we showed 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 the islets from 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.

摘要

缺乏 SPARC 的小鼠表现出葡萄糖耐量受损和胰岛素分泌受损，但潜在机制尚不清楚。在这里，我们表明 SPARC 增强了毒蕈碱受体激动剂 oxotremorine-M 对培养的小鼠胰岛中胰岛素分泌的促进作用。SPARC 的过表达下调了 RGS4，β 细胞 M3 毒蕈碱受体的负调节剂。相反，Min6 细胞中 SPARC 的敲低上调了 RGS4。SPARC-/- 小鼠胰岛中 RGS4 上调，与葡萄糖刺激的胰岛素分泌 (GSIS) 减少相关。此外，抑制 RGS4 可恢复 SPARC-/- 小鼠胰岛中的 GSIS，并且 RGS4 的敲低部分降低了 SPARC 对 oxotremorine-M 刺激的胰岛素分泌的促进作用。PI3K 抑制剂 LY-294002 消除了 SPARC 诱导的 RGS4 下调。总之，我们的数据表明 SPARC 通过抑制胰腺 β 细胞中的 RGS4 促进了 GSIS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/30818a7873e8/41598_2020_74593_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/c75b70c5cb7e/41598_2020_74593_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/464248a73fca/41598_2020_74593_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/49da25d5711f/41598_2020_74593_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/5d4024262704/41598_2020_74593_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/345aef74784f/41598_2020_74593_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/30818a7873e8/41598_2020_74593_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/c75b70c5cb7e/41598_2020_74593_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/464248a73fca/41598_2020_74593_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/49da25d5711f/41598_2020_74593_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/5d4024262704/41598_2020_74593_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/345aef74784f/41598_2020_74593_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/7567887/30818a7873e8/41598_2020_74593_Fig6_HTML.jpg

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