Proteomics

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MiR-17-92/106b regulate beta cell mitotic checkpoint and insulin secretion


ABSTRACT: Adult beta cells in the pancreas are the sole source of insulin in our body. Beta cell loss or increased demand for insulin, impose metabolic challenges because adult beta cells are generally quiescent and infrequently re-enter the cell division cycle. miR-17-92/106b is a family of proto-oncogene microRNAs, that regulate proliferation in normal tissues and in cancer. Here, we employ mouse genetics to demonstrate a critical role for miR-17-92/106b in glucose homeostasis and in controlling insulin secretion. Mass spectrometry analysis was performed on miR-17-92LoxP/LoxP;106-25-/- MEF lysate, without or with CRE-Adenovirus. miR-17-92LoxP/LoxP;106-25+/+ MEFs with GFP-Adenovirus served as controls. We demonstrate that miR-17-92/106b regulate the adult beta cell mitotic checkpoint and that miR-17-92/106b deficiency results in reduction in beta cell mass in-vivo. Furthermore, protein kinase A (PKA) is a new relevant molecular pathway downstream of miR-17-92/106b in control of adult beta cell division and glucose homeostasis. Therefore, contributes to the understanding of proto-oncogene miRNAs in the normal, untransformed endocrine pancreas, and illustrates new genetic means for regulation of beta cell mitosis and function by non-coding RNAs.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Alon Savidor  

LAB HEAD: Eran Hornstein

PROVIDER: PXD012610 | Pride | 2019-06-17

REPOSITORIES: Pride

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Publications

miR-17-92 and miR-106b-25 clusters regulate beta cell mitotic checkpoint and insulin secretion in mice.

Mandelbaum Amitai D AD   Kredo-Russo Sharon S   Aronowitz Danielle D   Myers Nadav N   Yanowski Eran E   Klochendler Agnes A   Swisa Avital A   Dor Yuval Y   Hornstein Eran E  

Diabetologia 20190611 9


<h4>Aims/hypothesis</h4>Adult beta cells in the pancreas are the sole source of insulin in the body. Beta cell loss or increased demand for insulin impose metabolic challenges because adult beta cells are generally quiescent and infrequently re-enter the cell division cycle. The aim of this study is to test the hypothesis that a family of proto-oncogene microRNAs that includes miR-17-92 and miR-106b-25 clusters regulates beta cell proliferation or function in the adult endocrine pancreas.<h4>Met  ...[more]

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