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miR-375 maintains normal pancreatic α- and β-cell mass

Item Type:Article
Title:miR-375 maintains normal pancreatic α- and β-cell mass
Creators Name:Poy, M.N. and Hausser, J. and Trajkovski, M. and Braun, M. and Collins, S. and Rorsman, P. and Zavolan, M. and Stoffel, M.
Abstract:Altered growth and development of the endocrine pancreas is a frequent cause of the hyperglycemia associated with diabetes. Here we show that microRNA-375 (miR-375), which is highly expressed in pancreatic islets, is required for normal glucose homeostasis. Mice lacking miR-375 (375KO) are hyperglycemic, exhibit increased total pancreatic alpha-cell numbers, fasting and fed plasma glucagon levels, and increased gluconeogenesis and hepatic glucose output. Furthermore, pancreatic beta-cell mass is decreased in 375KO mice as a result of impaired proliferation. In contrast, pancreatic islets of obese mice (ob/ob), a model of increased beta-cell mass, exhibit increased expression of miR-375. Genetic deletion of miR-375 from these animals (375/ob) profoundly diminished the proliferative capacity of the endocrine pancreas and resulted in a severely diabetic state. Bioinformatic analysis of transcript data from 375KO islets revealed that miR-375 regulates a cluster of genes controlling cellular growth and proliferation. These data provide evidence that miR-375 is essential for normal glucose homeostasis, alpha- and beta-cell turnover, and adaptive beta-cell expansion in response to increasing insulin demand in insulin resistance.
Keywords:Diabetes, Glucagon, microRNA, Islet, Proliferation, Blood Glucose, Cell Proliferation, Glucagon-Secreting Cells, Homeostasis, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Knockout Mice, Obese Mice, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:106
Number:14
Page Range:5813-5818
Date:7 April 2009
Official Publication:https://doi.org/10.1073/pnas.0810550106
PubMed:View item in PubMed

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