MicroRNA-17-92 cluster regulates pancreatic beta-cell proliferation and adaptation.
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.
['Chen|Yaxi|Y|', 'Tian|Li|L|', 'Wan|Shan|S|', 'Xie|Ying|Y|', 'Chen|Xiang|X|', 'Ji|Xiao|X|', 'Zhao|Qian|Q|', 'Wang|Chunyu|C|', 'Zhang|Kun|K|', 'Hock|Janet M|JM|', 'Tian|Haoming|H|', 'Yu|Xijie|X|']
D000222:Adaptation, Physiological D000818:Animals D017209:Apoptosis D002460:Cell Line D049109:Cell Proliferation D059305:Diet, High-Fat D017353:Gene Deletion D005786:Gene Expression Regulation D005947:Glucose D018149:Glucose Intolerance D007328:Insulin D000078790:Insulin Secretion D050417:Insulin-Secreting Cells D008297:Male D008810:Mice, Inbred C57BL D018345:Mice, Knockout D035683:MicroRNAs D010641:Phenotype D015398:Signal Transduction
Pancreatic beta-cells Proliferation Adaptation MiR-17-92 PTEN