Autocrine role of interleukin-13 on skeletal muscle glucose metabolism in type 2 diabetic patients involves microRNA let-7

作者：Jiang Lake Q; Franck Niclas; Egan Brendan; Sjogren Rasmus J O; Katayama Mutsumi; Duque Guimaraes Daniella; Arner Peter; Zierath Juleen R; Krook Anna^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2013, 305(11): E1359-E1366.

DOI：10.1152/ajpendo.00236.2013

• cytokines
• diabetes
• glucose metabolism
• lipid metabolism
• gene expression

Low-grade inflammation associated with type 2 diabetes (T2DM) is postulated to exacerbate insulin resistance. We report that serum levels, as well as IL-13 secreted from cultured skeletal muscle, are reduced in T2DM vs. normal glucose-tolerant (NGT) subjects. IL-13 exposure increases skeletal muscle glucose uptake, oxidation, and glycogen synthesis via an Akt-dependent mechanism. Expression of microRNA let-7a and let-7d, which are direct translational repressors of the IL-13 gene, was increased in skeletal muscle from T2DM patients. Overexpression of let-7a and let-7d in cultured myotubes reduced IL-13 secretion. Furthermore, basal glycogen synthesis was reduced in cultured myotubes exposed to an IL-13-neutralizing antibody. Thus, IL-13 is synthesized and released by skeletal muscle through a mechanism involving let-7, and this effect is attenuated in skeletal muscle from insulin-resistant T2DM patients. In conclusion, IL-13 plays an autocrine role in skeletal muscle to increase glucose uptake and metabolism, suggesting a role in glucose homeostasis in metabolic disease.

• 出版日期2013-12