Argonaute2 Mediates Compensatory Expansion of the Pancreatic 尾 Cell

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• 作者：Sudhir聽G. Tattikota ; Thomas Rathjen ; Sarah聽J. McAnulty ; Hans-Hermann Wessels ; Ildem Akerman ; Martijn van聽de聽Bunt ; Jean Hausser ; Jonathan聽L.S. Esguerra ; Anne Musahl ; Amit聽K. P ; ey ; Xintian You ; Wei Chen ; Pedro聽L. Herrera ; Paul聽R. Johnson ; Donal O鈥機arroll ; Lena Eliasson ; Mihaela Zavolan ; Anna聽L. Gloyn ; Jorge Ferrer ; Ruby Shalom-Feuerstein ; Daniel Aberdam ; et al.
• 刊名：Cell Metabolism
• 出版年：7 January, 2014
• 年：2014
• 卷：19
• 期：1
• 页码：122-134
• 全文大小：1632 K

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Summary

Pancreatic 尾 cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in 尾 cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory 尾 cell expansion. Loss of Ago2 during insulin resistance blocked 尾 cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and 尾 cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.