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MicroRNA-7a regulates pancreatic beta cell function

Latreille, Mathieu; Hausser, Jean; Stuetzer, Ina; Zhang, Quan; Hastoy, Benoit; Gargani, Sofia; Kerr-Conte, Julie; Pattou, Francois; Zavolan, Mihaela and Esguerra, Jonathan LU , et al. (2014) In Journal of Clinical Investigation 124(6). p.2722-2735
Abstract
Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic beta cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of beta cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in beta cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates beta cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in... (More)
Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic beta cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of beta cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in beta cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates beta cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in beta cells developed diabetes due to impaired insulin secretion and beta cell dedifferentiation. Interestingly, perturbation of miR-7a expression in beta cells did not affect proliferation and apoptosis, indicating that miR-7 is dispensable for the maintenance of endocrine beta cell mass. Furthermore, we found that miR-7a levels are decreased in obese/ diabetic mouse models and human islets from obese and moderately diabetic individuals with compensated beta cell function. Our results reveal an interconnecting miR-7 genomic circuit that regulates insulin granule exocytosis in pancreatic beta cells and support a role for miR-7 in the adaptation of pancreatic p cell function in obesity and type 2 diabetes. (Less)
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type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Investigation
volume
124
issue
6
pages
2722 - 2735
publisher
The Journal of Clinical Investigation
external identifiers
  • wos:000336868800042
  • scopus:84900797916
ISSN
0021-9738
DOI
10.1172/JCI73066
language
English
LU publication?
yes
id
55f0316e-b7ae-4005-8dfd-502ffe845762 (old id 4549158)
date added to LUP
2014-08-01 07:38:08
date last changed
2017-10-08 03:57:54
@article{55f0316e-b7ae-4005-8dfd-502ffe845762,
  abstract     = {Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic beta cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of beta cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in beta cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates beta cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in beta cells developed diabetes due to impaired insulin secretion and beta cell dedifferentiation. Interestingly, perturbation of miR-7a expression in beta cells did not affect proliferation and apoptosis, indicating that miR-7 is dispensable for the maintenance of endocrine beta cell mass. Furthermore, we found that miR-7a levels are decreased in obese/ diabetic mouse models and human islets from obese and moderately diabetic individuals with compensated beta cell function. Our results reveal an interconnecting miR-7 genomic circuit that regulates insulin granule exocytosis in pancreatic beta cells and support a role for miR-7 in the adaptation of pancreatic p cell function in obesity and type 2 diabetes.},
  author       = {Latreille, Mathieu and Hausser, Jean and Stuetzer, Ina and Zhang, Quan and Hastoy, Benoit and Gargani, Sofia and Kerr-Conte, Julie and Pattou, Francois and Zavolan, Mihaela and Esguerra, Jonathan and Eliasson, Lena and Ruelicke, Thomas and Rorsman, Patrik and Stoffel, Markus},
  issn         = {0021-9738},
  language     = {eng},
  number       = {6},
  pages        = {2722--2735},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {MicroRNA-7a regulates pancreatic beta cell function},
  url          = {http://dx.doi.org/10.1172/JCI73066},
  volume       = {124},
  year         = {2014},
}