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A pancreatic islet-specific microRNA regulates insulin secretion

Poy, MN; Eliasson, Lena LU ; Krutzfeldt, J; Kuwajima, S; Ma, Xiaosong LU ; MacDonald, Patrick LU ; Pfeffer, B; Tuschl, T; Rajewsky, N and Rorsman, Patrik LU , et al. (2004) In Nature 432(7014). p.226-230
Abstract
MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression(1). Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes(2-4). To study the role of miRNAs in pancreatic endocrine cells we cloned and identified a novel, evolutionarily conserved and islet-specific miRNA (miR-375). Here we show that overexpression of miR-375 suppressed glucose-induced insulin secretion, and conversely, inhibition of endogenous miR-375 function enhanced insulin secretion. The mechanism by which secretion is modified by miR-375 is independent of changes in glucose... (More)
MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression(1). Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes(2-4). To study the role of miRNAs in pancreatic endocrine cells we cloned and identified a novel, evolutionarily conserved and islet-specific miRNA (miR-375). Here we show that overexpression of miR-375 suppressed glucose-induced insulin secretion, and conversely, inhibition of endogenous miR-375 function enhanced insulin secretion. The mechanism by which secretion is modified by miR-375 is independent of changes in glucose metabolism or intracellular Ca2+-signalling but correlated with a direct effect on insulin exocytosis. Myotrophin (Mtpn) was predicted to be and validated as a target of miR-375. Inhibition of Mtpn by small interfering (si) RNA mimicked the effects of miR-375 on glucose-stimulated insulin secretion and exocytosis. Thus, miR-375 is a regulator of insulin secretion and may thereby constitute a novel pharmacological target for the treatment of diabetes. (Less)
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publication status
published
subject
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Nature
volume
432
issue
7014
pages
226 - 230
publisher
Nature Publishing Group
external identifiers
  • wos:000225020200048
  • pmid:15538371
  • scopus:9144270691
ISSN
0028-0836
DOI
10.1038/nature03076
language
English
LU publication?
yes
id
346ccc2b-37a2-440d-825a-9184ea38ac21 (old id 263672)
date added to LUP
2007-10-30 07:39:28
date last changed
2017-12-10 03:53:25
@article{346ccc2b-37a2-440d-825a-9184ea38ac21,
  abstract     = {MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression(1). Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes(2-4). To study the role of miRNAs in pancreatic endocrine cells we cloned and identified a novel, evolutionarily conserved and islet-specific miRNA (miR-375). Here we show that overexpression of miR-375 suppressed glucose-induced insulin secretion, and conversely, inhibition of endogenous miR-375 function enhanced insulin secretion. The mechanism by which secretion is modified by miR-375 is independent of changes in glucose metabolism or intracellular Ca2+-signalling but correlated with a direct effect on insulin exocytosis. Myotrophin (Mtpn) was predicted to be and validated as a target of miR-375. Inhibition of Mtpn by small interfering (si) RNA mimicked the effects of miR-375 on glucose-stimulated insulin secretion and exocytosis. Thus, miR-375 is a regulator of insulin secretion and may thereby constitute a novel pharmacological target for the treatment of diabetes.},
  author       = {Poy, MN and Eliasson, Lena and Krutzfeldt, J and Kuwajima, S and Ma, Xiaosong and MacDonald, Patrick and Pfeffer, B and Tuschl, T and Rajewsky, N and Rorsman, Patrik and Stoffel, M},
  issn         = {0028-0836},
  language     = {eng},
  number       = {7014},
  pages        = {226--230},
  publisher    = {Nature Publishing Group},
  series       = {Nature},
  title        = {A pancreatic islet-specific microRNA regulates insulin secretion},
  url          = {http://dx.doi.org/10.1038/nature03076},
  volume       = {432},
  year         = {2004},
}