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AJP: Endocrinology and Metabolism

Year: 2010  |  Volume: 299  |  Issue: 5  |  Page No.: 794 - 801

NF-{kappa}B activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions

P Tantiwong, K Shanmugasundaram, A Monroy, S Ghosh, M Li, R. A DeFronzo, E Cersosimo, A Sriwijitkamol, S Mohan and N. Musi

Abstract

NF-B is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-B activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-B activity in muscle. The effect that exercise has on NF-B activity/signaling also is not clear. We measured NF-B DNA-binding activity and the mRNA level of putative NF-B-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-B activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-B activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-B activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-B activity in muscle. Acute exercise stimulates NF-B in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-B activity, which could be explained by the already elevated NF-B activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-B activity, suggesting that other factors promote gene expression of these cytokines during exercise.

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