Amino acids-Rab1A-mTORC1 signaling controls whole-body glucose homeostasis
Xin Zhang, Xiaowen Wang, Ziqiang Yuan, Sarah J. Radford, Chen Liu, Steven K. Libutti, X.F. Steven Zheng
Abstract
mice are viable but become hyperglycemic and glucose intolerant due to impaired insulin transcription and β-cell proliferation and maintenance. Mechanistically, Rab1A mediates AA-mTORC1 signaling, particularly branched chain amino acids (BCAA), to regulate the stability and localization of the insulin transcription factor Pdx1. Collectively, these results reveal a physiological role of aa-Rab1A-mTORC1 signaling in the control of whole-body glucose homeostasis in mammals. Intriguingly, Rab1A expression is reduced in β-cells of type 2 diabetes (T2D) patients, which is correlated with loss of insulin expression, suggesting that Rab1A downregulation contributes to T2D progression.