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

Diabetologia. 2003 Oct;46(10):1324-8. doi: 10.1007/s00125-003-1196-3. Epub 2003 Aug 23.

Abstract

Aims/hypothesis: 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.

Methods: 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.

Results: 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.

Conclusion/interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / metabolism*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism*
  • Muscle, Skeletal / metabolism*
  • Phosphorylation / drug effects
  • Ribonucleotides / pharmacology
  • Signal Transduction*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Hypoglycemic Agents
  • Insulin
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • AICA ribonucleotide