Intestinal mTOR regulates GLP-1 production in mouse L cells
Intestinal mTOR regulates GLP-1 production in mouse L cells
复制标题
肠道 mTOR 调节小鼠 L 细胞中 GLP-1 的产生
DOI：
10.1007/s00125-015-3632-6
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发表时间：
2015-06
期刊：
影响因子：
8.2
通讯作者：
Zhang Weizhen
中科院分区：
文献类型：
--
作者：
Xu Geyang;Li Ziru;Ding Li;Tang Hong;Guo Song;Liang Hongbin;Wang Huadong;Zhang Weizhen
Aims/hypothesisGlucagon-like peptide (GLP-1), an intestinal incretin produced in L cells through proglucagon processing, is released in response to meal intake. The intracellular mechanism by which L cells sense the organism energy level to coordinate the production of GLP-1 remains unclear. Mechanistic target of rapamycin (mTOR) is an intracellular fuel sensor critical for energy homeostasis. In this study, we investigated whether intestinal mTOR regulates GLP-1 production in L cells.MethodsThe effects of mTOR on GLP-1 production were examined in lean- or high-fat diet (HFD) induced diabetic C57/BL6,db/db,Neurog3-Tsc1−/−mice, and STC-1 cells. GLP-1 expression was investigated by real-time PCR and western blotting. Plasma GLP-1 and insulin were detected by enzyme immunoassay and radioimmunoassay, respectively.ResultsFasting downregulated mTOR activity, which was associated with a decrement of intestinal proglucagon and circulating GLP-1. Upon re-feeding, these alterations returned to the levels of fed animals. In HFD induced diabetic mice, ileal mTOR signalling, proglucagon and circulating GLP-1 were significantly decreased. Inhibition of mTOR signalling by rapamycin decreased levels of intestinal and plasma GLP-1 in both normal and diabetic mice. Activation of the intestinal mTOR signalling byl-leucine orTsc1gene deletion increased levels of intestinal proglucagon and plasma GLP-1. Overexpression of mTOR stimulated proglucagon promoter activity and GLP-1 production, whereas inhibition of mTOR activity by overexpression of tuberous sclerosis 1 (TSC1) or TSC2 decreased proglucagon promoter activity and GLP-1 production in STC-1 cells.Conclusions/interpretationmTOR may link energy supply with the production of GLP-1 in L cells.
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影响因子：
4.9
作者：
Verdich, C;Toubro, S;Astrup, A
通讯作者：
Astrup, A
Nesfatin-1 对血糖稳态的外周影响
影响因子：
3.7
作者：
Li Z;Gao L;Tang H;Yin Y;Xiang X;Li Y;Zhao J;Mulholland M;Zhang W
通讯作者：
Zhang W
DOI：
10.1016/s0021-9258(19)50075-8
发表时间：
1992-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ying‐Chu Lee;S. Asa;D. Drucker
通讯作者：
Ying‐Chu Lee;S. Asa;D. Drucker
DOI：
10.1016/s0021-9258(18)67561-1
发表时间：
1986-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
D. Drucker;S. Mojsov;J. Habener
通讯作者：
D. Drucker;S. Mojsov;J. Habener
影响因子：
7.7
作者：
Matveyenko AV;Dry S;Cox HI;Moshtaghian A;Gurlo T;Galasso R;Butler AE;Butler PC
通讯作者：
Butler PC