title: MicroRNA-17-92 cluster regulates pancreatic beta-cell proliferation and adaptation.
abstract: MiR-17-92 cluster contributes to the regulation of mammalian development, aging and tumorigenesis. The functional roles of miR-17-92 in pancreatic beta-cells are largely unknown. In this study, we found that conditional deletion of miR-17-92 in mouse pancreatic beta-cells (miR-17-92βKO) significantly reduces glucose tolerance and the first phase of insulin secretion, despite normal ad libitum fed and fasting glucose levels. Proliferation is down-regulated in pancreatic beta-cells after deleting miR-17-92. MiR-17-92βKO mice show higher phosphatase and tensin homologue (PTEN) and lower phosphorylated AKT in islets. Under high fat diet challenge for 16 weeks, miR-17-92βKO mice lose compensation and exhibit higher glucose levels, and lower insulin secretion. Collectively, these data suggest that miR-17-92 is a critical contributor to molecular mechanisms regulating glucose-stimulated insulin secretion and pancreatic beta-cell adaptation under metabolic stress.
authors: Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, PR China.
authors: Yaxi
authors: Y
authors: Chen
authors: Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, PR China.
authors: Li
authors: L
authors: Tian
authors: Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, PR China.
authors: Shan
authors: S
authors: Wan
authors: Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, PR China.
authors: Ying
authors: Y
authors: Xie
authors: Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, PR China.
authors: Xiang
authors: X
authors: Chen
authors: Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, PR China.
authors: Xiao
authors: X
authors: Ji
authors: Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, PR China.
authors: Qian
authors: Q
authors: Zhao
authors: Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, PR China.
authors: Chunyu
authors: C
authors: Wang
authors: Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, PR China.
authors: Kun
authors: K
authors: Zhang
authors: The Polis Center, Indiana University-Purdue University Indianapolis, 1200 Waterway Blvd # 100, Indianapolis, IN 46202, USA.
authors: Janet M
authors: JM
authors: Hock
authors: Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, PR China.
authors: Haoming
authors: H
authors: Tian
authors: Laboratory of Endocrinology and Metabolism, Department of Endocrinology, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, PR China. Electronic address: xijieyu@scu.edu.cn.
authors: Xijie
authors: X
authors: Yu
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D059305:Diet, High-Fat; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D018149:Glucose Intolerance / Q000235:genetics / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007328:Insulin; C575895:MIRN17-92 microRNA, mouse; D035683:MicroRNAs; D005947:Glucose
keywords: Adaptation; MiR-17-92; PTEN; Pancreatic beta-cells; Proliferation