title: TCTP is essential for β-cell proliferation and mass expansion during development and β-cell adaptation in response to insulin resistance.
abstract: The perinatal period is critical for β-cell mass establishment, which is characterized by a transient burst in proliferation to increase β-cell mass in response to the need for glucose homeostasis throughout life. In adulthood, the ability of β-cells to grow, proliferate, and expand their mass is also characteristic of pathological states of insulin resistance. Translationally controlled tumor-associated protein (TCTP), an evolutionarily highly conserved protein that is implicated in cell growth and proliferation, has been identified as a novel glucose-regulated survival-supporting protein in pancreatic β-cells. In this study, the enhanced β-cell proliferation detected both during the perinatal developmental period and in insulin-resistant states in high-fat diet-fed mice was found to parallel the expression of TCTP in pancreatic β-cells. Specific knockout of TCTP in β-cells led to increased expression of total and nuclear Forkhead box protein O1 and tumor suppressor protein 53, and decreased expression of p70S6 kinase phosphorylation and cyclin D2 and cyclin-dependent kinase 2. This resulted in decreased β-cell proliferation and growth, reduced β-cell mass, and insulin secretion. Together, these effects led to hyperglycemia. These observations suggest that TCTP is essential for β-cell mass expansion during development and β-cell adaptation in response to insulin resistance.
authors.affiliation: PhD Program in Pharmacology and Toxicology (M.J.-T., S.-H.C.) and Department of Pharmacology (S.-S.W., S.-H.C.), School of Medicine, Tzu Chi University, Hualien 970, Taiwan; Departments of Emergency Medicine (M.J.-T.) and Medical Research (M.-J.W.), Neuro-Medical Scientific Center, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan; Institutes of Molecular Biology (H.-F.Y.-Y.), Academia Sinica, Taipei 115, Taiwan; and Department of Life Science and Institute of Molecular Biology (M.-K.C.), National Chung-Cheng University, Chia-Yi 621, Taiwan.
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Hsin-Fang
authors.initials: HF
authors.lastname: Yang-Yen
authors.forename: Ming-Ko
authors.initials: MK
authors.lastname: Chiang
authors.forename: Mei-Jen
authors.initials: MJ
authors.lastname: Wang
authors.forename: Shiou-Shian
authors.initials: SS
authors.lastname: Wu
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation; D018149:Glucose Intolerance / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D014408:Biomarkers, Tumor; D001786:Blood Glucose; D007328:Insulin; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1