Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7353
pubmed:dateCreated
2011-7-1
pubmed:abstractText
Defects in insulin signalling are among the most common and earliest defects that predispose an individual to the development of type 2 diabetes. MicroRNAs have been identified as a new class of regulatory molecules that influence many biological functions, including metabolism. However, the direct regulation of insulin sensitivity by microRNAs in vivo has not been demonstrated. Here we show that the expression of microRNAs 103 and 107 (miR-103/107) is upregulated in obese mice. Silencing of miR-103/107 leads to improved glucose homeostasis and insulin sensitivity. In contrast, gain of miR-103/107 function in either liver or fat is sufficient to induce impaired glucose homeostasis. We identify caveolin-1, a critical regulator of the insulin receptor, as a direct target gene of miR-103/107. We demonstrate that caveolin-1 is upregulated upon miR-103/107 inactivation in adipocytes and that this is concomitant with stabilization of the insulin receptor, enhanced insulin signalling, decreased adipocyte size and enhanced insulin-stimulated glucose uptake. These findings demonstrate the central importance of miR-103/107 to insulin sensitivity and identify a new target for the treatment of type 2 diabetes and obesity.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
474
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
649-53
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21654750-Adipocytes, pubmed-meshheading:21654750-Animals, pubmed-meshheading:21654750-Caveolin 1, pubmed-meshheading:21654750-Cell Size, pubmed-meshheading:21654750-Diabetes Mellitus, Type 2, pubmed-meshheading:21654750-Disease Models, Animal, pubmed-meshheading:21654750-Gene Expression, pubmed-meshheading:21654750-Gene Expression Regulation, pubmed-meshheading:21654750-Gene Silencing, pubmed-meshheading:21654750-Glucose, pubmed-meshheading:21654750-Homeostasis, pubmed-meshheading:21654750-Hyperglycemia, pubmed-meshheading:21654750-Insulin, pubmed-meshheading:21654750-Liver, pubmed-meshheading:21654750-Male, pubmed-meshheading:21654750-Mice, pubmed-meshheading:21654750-Mice, Inbred C57BL, pubmed-meshheading:21654750-MicroRNAs, pubmed-meshheading:21654750-Signal Transduction, pubmed-meshheading:21654750-Up-Regulation
pubmed:year
2011
pubmed:articleTitle
MicroRNAs 103 and 107 regulate insulin sensitivity.
pubmed:affiliation
Institute for Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli Strasse 16, CH-8093 Zurich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't