title: TSC1-mTOR signaling determines the differentiation of islet cells.
abstract: Neurogenin3-driven deletion of tuberous sclerosis complex 1 (Tsc1) activated mechanistic target of rapamycin complex 1 (mTORC1) measured by the upregulation 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.
authors.affiliation: Department of Physiology and PathophysiologyPeking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Physiology and PathophysiologyPeking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Physiology and PathophysiologyPeking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Physiology and PathophysiologyPeking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology and PathophysiologyPeking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Physiology and PathophysiologyPeking University Health Science Center, and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China weizhenzhang@bjmu.edu.cn.|Department of SurgeryUniversity of Michigan Medical Center, Ann Arbor, Michigan, USA.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001786:Blood Glucose; D002454:Cell Differentiation / Q000502:physiology*; D059305:Diet, High-Fat; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013004:Somatostatin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001786:Blood Glucose; D005934:Glucagon; D007328:Insulin; D009419:Nerve Tissue Proteins; D013004:Somatostatin; D058570:TOR Serine-Threonine Kinases; D019098:Telomerase; C407737:Neurog3 protein, mouse; C509187:Tert protein, mouse
keywords: diabetes; differentiation and development; glucose metabolism; insulin; mechanistic target of rapamycin complex 1