TSC1-mTOR signaling determines the differentiation of islet cells
- L Ding, Physiology and Pathophysiology, Peking University Health Science Centre, Beijing, China
- Y Yin, Physiology and Pathophysiology, Peking University Health Science Centre, Beijing, China
- L Han, Physiology and Pathophysiology, Peking University Health Science Centre, Beijing, China
- Y Li, Department of Physiology and Pathophysiology, PekingUniversityHealth Science Center, China, China
- J Zhao, Department of Physiology and Pathophysiology, PekingUniversityHealth Science Center, China, China
- W Zhang, Surgery, the University of Michigna, Ann Arbor, United States
- Correspondence: Weizhen Zhang, Email: weizhenz{at}umich.edu
Abstract
Neurogenin3-driven deletion of tuberous sclerosis complex 1 (Tsc1) activated mechanistic target of rapamycin complex 1 (mTORC1) measured by up-regulation of mTOR and S6 phosphorylation in islet cells. Neurogenin3-Tsc1-/- mice demonstrated a significant increase in average islet size and mean area of individual islet cell. Insulin mRNA and plasma insulin levels increased significantly after weaning. Glucagon mRNA and plasma levels increased in neonate followed by modest reduction in adult. Somatostatin mRNA and plasma levels markedly increased. Neurogenin3-Tsc1-/- mice fed standard chow demonstrated a significant improvement in glucose tolerance and no alteration in insulin sensitivity. In Neurogenin3-Tsc1-/- mice fed 45% high fat diets, both glucose tolerance and insulin sensitivity were significantly impaired. Rapamycin reversed the activation of mTORC1, attenuated β cells hypertrophy and abolished the improvement of glucose tolerance. TSC1-mTORC1 signaling plays an important role in the development of pancreatic endocrine cells, and in the regulation of glucose metabolism.
- Received 21 June 2016
- Received in final form 7 October 2016
- Accepted 17 October 2016
- Accepted Preprint first posted online on 17 October 2016
