Nature Article Implicates microRNAs in the Pathogenesis of Obesity and Type ... ( LA JOLLA Calif. and CAMBRIDGE Mass. J...)

Nature Article Implicates microRNAs in the Pathogenesis of Obesity and Type 2 Diabetes

Date:6/8/2011

LA JOLLA, Calif., and CAMBRIDGE, Mass., June 8, 2011 /PRNewswire/ -- Regulus Therapeutics Inc., a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, and Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced the publication in Nature of new pre-clinical data in mice about the antagonism of microRNA-103 and microRNA-107 (miR-103/107). Data from a collaborative study performed by Regulus, Alnylam and ETH Zurich demonstrated that antagonism of miR-103/107 with proprietary chemically modified anti-miR oligonucleotides could promote insulin signaling in both liver and adipose tissue. Silencing miR-103/107 in animal models of obesity improved glucose homeostasis, suggesting that these microRNAs are potential targets for the treatment of diabetes.

Defects in insulin signaling are among the most common and earliest defects that predispose an individual to the development of type 2 diabetes. The new findings demonstrated that miR-103/107 are upregulated in obese mice, and silencing with anti-miRs could improve glucose homeostasis and insulin sensitivity, while gain of function in liver or fat caused impaired glucose homeostasis. Direct targets of miR-103/107 identified include caveolin-1, a critical regulator of the insulin receptor. Upon miR-103/107 inactivation, caveolin-1 is upregulated, resulting in stabilization of the insulin receptor, enhanced insulin signaling, decreased adipocyte size and enhanced insulin-stimulated glucose uptake.

"microRNAs are a new class of regulatory molecules that influence many biological functions, including metabolism. These studies suggest t
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SOURCE Regulus Therapeutics Inc.
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