Molecular mechanisms responsible for Intramyocellular lipids accumulation in human muscle during sarcopenia and type 2 diabetes

Abstract

Aging and type 2 diabetes are the major public health problem of the 21st century. The phenotypic similarity of skeletal muscle between sarcopenia and Type 2 diabetes is the accumulation of intramyocellular lipids (IMCL) in correlation with insulin resistance. Aging promotes coexpression of myogenic and adipogenic programs in murine myoblasts which may contribute to increased IMCL accumulation described in aged mouse muscles. Increase of IMCL has been proposed as biomarker for insulin resistance which is a pivotal feature in the pathogenesis of type 2 diabetes. The insulin-stimulated rate of glucose uptake by muscleis reduced in the insulin-resistantsubjectsand is associated with an increase in the IMCL content. Wnt 10b signalling pathway has been well characterized during aging in mice for its function as an inhibitor of the adipogenic program in muscle. As such Wnt 10b could be a good candidate to reduce IMCL accumulation and increase insulin sensitivity in human muscle. The aim of this study is to explore the links between Wnt 10b signalling pathway and insulin action in human muscle by using primary human muscle cells derived from young, middle aged, old, insulin-sensitive and type 2 diabetic subjects. We have already purified and characterized muscle cells from old and type 2 diabetic subjects. We would like to be able to identify new attractive targets for drug development in type 2 diabetes in humans. Source of research support: AFM (Association Francaise contre la Myopathie).