p38 MAPK activation upregulates pro-inflammatory pathways in skeletal muscle cells from insulin resistant type 2 diabetic patients

Skeletal muscle is the key site of peripheral insulin resistance in type 2 diabetes. Insulin-stimulated glucose uptake is decreased in differentiated diabetic myotubes in keeping with a retained genetic/epigenetic defect of insulin action. Microarray analysis was used to investigate differences in gene expression with differentiation in diabetic cultures compared to controls. Muscle biopsies were obtained from type 2 diabetics with a family history of type 2 diabetes and clinical evidence of marked insulin resistance and age-and BMI-matched controls. Muscle cell cultures were derived from these biopsies and RNA extracted from both myoblasts and myotubes for gene expression analysis.