Aberrant p38 mitogen-activated protein kinase signalling in skeletal muscle from Type 2 diabetic patients

• DOI: 10.1007/s00125-003-1196-3
• Publication Date: 2003-10-27T16:30:15Z
• Authors: H. A. Koistinen; A. V. Chibalin; J. R. Zierath
• Keywords: 0303 health sciences; Middle Aged; Ribonucleotides; Aminoimidazole Carboxamide; p38 Mitogen-Activated Protein Kinases; 3. Good health; 03 medical and health sciences; Diabetes Mellitus, Type 2; Case-Control Studies; Humans; Hypoglycemic Agents; Insulin; Mitogen-Activated Protein Kinases; Phosphorylation; Muscle, Skeletal; Signal Transduction

p38 mitogen activated protein kinase (MAPK) is generally thought to facilitate signal transduction to genomic, rather than metabolic responses. However, recent evidence implicates a role for p38 MAPK in the regulation of glucose transport; a site of insulin resistance in Type 2 diabetes. Thus we determined p38 MAPK protein expression and phosphorylation in skeletal muscle from Type 2 diabetic patients and non-diabetic subjects.In vitro effects of insulin (120 nmol/l) or AICAR (1 mmol/l) on p38 MAPK expression and phosphorylation were determined in skeletal muscle from non-diabetic (n=6) and Type 2 diabetic (n=9) subjects.p38 MAPK protein expression was similar between Type 2 diabetic patients and non-diabetic subjects. Insulin exposure increased p38 MAPK phosphorylation in non-diabetic, but not in Type 2 diabetic patients. In contrast, basal phosphorylation of p38 MAPK was increased in skeletal muscle from Type 2 diabetic patients.Insulin increases p38 MAPK phosphorylation in skeletal muscle from non-diabetic subjects, but not in Type 2 diabetic patients. However, basal p38 MAPK phosphorylation is increased in skeletal muscle from Type 2 diabetic patients. Thus, aberrant p38 MAPK signalling might contribute to the pathogenesis of insulin resistance.