Reference - Detail
| RRC ID | 82622 |
|---|---|
| Author | Bozadjieva N, Blandino-Rosano M, Chase J, Dai XQ, Cummings K, Gimeno J, Dean D, Powers AC, Gittes GK, Rüegg MA, Hall MN, MacDonald PE, Bernal-Mizrachi E. |
| Title | Loss of mTORC1 signaling alters pancreatic α cell mass and impairs glucagon secretion. |
| Journal | J Clin Invest |
| Abstract |
Glucagon plays a major role in the regulation of glucose homeostasis during fed and fasting states. However, the mechanisms responsible for the regulation of pancreatic α cell mass and function are not completely understood. In the current study, we identified mTOR complex 1 (mTORC1) as a major regulator of α cell mass and glucagon secretion. Using mice with tissue-specific deletion of the mTORC1 regulator Raptor in α cells (αRaptorKO), we showed that mTORC1 signaling is dispensable for α cell development, but essential for α cell maturation during the transition from a milk-based diet to a chow-based diet after weaning. Moreover, inhibition of mTORC1 signaling in αRaptorKO mice and in WT animals exposed to chronic rapamycin administration decreased glucagon content and glucagon secretion. In αRaptorKO mice, impaired glucagon secretion occurred in response to different secretagogues and was mediated by alterations in KATP channel subunit expression and activity. Additionally, our data identify the mTORC1/FoxA2 axis as a link between mTORC1 and transcriptional regulation of key genes responsible for α cell function. Thus, our results reveal a potential function of mTORC1 in nutrient-dependent regulation of glucagon secretion and identify a role for mTORC1 in controlling α cell-mass maintenance. |
| Volume | 127(12) |
| Pages | 4379-4393 |
| Published | 2017-12-1 |
| PII | 90004 |
| PMID | 29106387 |
| PMC | PMC5707167 |
| MeSH | Animals Glucagon / metabolism* Glucagon-Secreting Cells / cytology Glucagon-Secreting Cells / metabolism* Hepatocyte Nuclear Factor 3-beta / genetics Hepatocyte Nuclear Factor 3-beta / metabolism Mechanistic Target of Rapamycin Complex 1 / genetics Mechanistic Target of Rapamycin Complex 1 / metabolism* Mice Mice, Knockout Regulatory-Associated Protein of mTOR / genetics Regulatory-Associated Protein of mTOR / metabolism* Signal Transduction* |
| IF | 11.864 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 21 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC00806 |