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

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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