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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7014
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pubmed:dateCreated |
2004-11-11
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pubmed:abstractText |
MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression. Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes. 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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1476-4687
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pubmed:author |
pubmed-author:EliassonLenaL,
pubmed-author:KrutzfeldtJanJ,
pubmed-author:KuwajimaSatoruS,
pubmed-author:MaXiaosongX,
pubmed-author:MacdonaldPatrick EPE,
pubmed-author:PfefferSébastienS,
pubmed-author:PoyMatthew NMN,
pubmed-author:RajewskyNikolausN,
pubmed-author:RorsmanPatrikP,
pubmed-author:StoffelMarkusM,
pubmed-author:TuschlThomasT
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pubmed:issnType |
Electronic
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pubmed:day |
11
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pubmed:volume |
432
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
226-30
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15538371-Animals,
pubmed-meshheading:15538371-Calcium Signaling,
pubmed-meshheading:15538371-Cell Line,
pubmed-meshheading:15538371-Cloning, Molecular,
pubmed-meshheading:15538371-Diabetes Mellitus,
pubmed-meshheading:15538371-Exocytosis,
pubmed-meshheading:15538371-Gene Expression,
pubmed-meshheading:15538371-Gene Silencing,
pubmed-meshheading:15538371-Gene Therapy,
pubmed-meshheading:15538371-Glucose,
pubmed-meshheading:15538371-Insulin,
pubmed-meshheading:15538371-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:15538371-Islets of Langerhans,
pubmed-meshheading:15538371-Mice,
pubmed-meshheading:15538371-MicroRNAs,
pubmed-meshheading:15538371-Organ Specificity,
pubmed-meshheading:15538371-Potassium Chloride,
pubmed-meshheading:15538371-Substrate Specificity,
pubmed-meshheading:15538371-Tolbutamide
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pubmed:year |
2004
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pubmed:articleTitle |
A pancreatic islet-specific microRNA regulates insulin secretion.
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pubmed:affiliation |
Laboratory of Metabolic Diseases and Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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