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miR-375 maintains normal pancreatic alpha- and beta-cell mass.

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.

Pubmed ID: 19289822

Authors

  • Poy MN
  • Hausser J
  • Trajkovski M
  • Braun M
  • Collins S
  • Rorsman P
  • Zavolan M
  • Stoffel M

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

April 7, 2009

Associated Grants

  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Animals
  • Blood Glucose
  • Cell Proliferation
  • Glucagon-Secreting Cells
  • Homeostasis
  • Insulin
  • Insulin-Secreting Cells
  • Islets of Langerhans
  • Mice
  • Mice, Knockout
  • Mice, Obese
  • MicroRNAs