Reduced glycogen synthase activity in skeletal muscle from obese patients with and without type 2 (non-insulin-dependent) diabetes mellitus

Diabetologia. 1991 Apr;34(4):239-45. doi: 10.1007/BF00405082.


In order to evaluate the importance of a defect in insulin mediated non-oxidative glucose metabolism and glycogen synthase activity in skeletal muscles in obese subjects with and without Type 2 (non-insulin-dependent) diabetes mellitus we studied: 10 lean and 10 obese control subjects and 12 obese diabetic patients using the euglycaemic hyperinsulinaemic clamp technique (basal, 20 mU.(m2)-1.min-1, 80 mU.(m2)-1.min-1) in combination with indirect calorimetry. Muscle biopsies were taken from m. vastus lateralis at each insulin level. We found that non-oxidative glucose metabolism could be stimulated by insulin in all three groups (p less than 0.01). The values obtained at the highest insulin levels (around 140 microU/ml) were lower in both obese groups compared to the lean control subjects (118 +/- 21, 185 +/- 31, 249 +/- 14 mg.(m2)-1.min-1 (p less than 0.01]. Insulin stimulation of the glycogen synthase activity at a glucose-6-phosphate concentration of 0.1 mmol/l was absent in both obese groups, while activities increased significantly in the lean control subjects (19.6 +/- 4.2% to 45.6 +/- 6.8%, p less than 0.01). Glycogen synthase activities at the highest insulin concentrations only differed significantly between lean control subjects and obese diabetic patients (45 +/- 7% and 31 +/- 5%, p less than 0.05). We conclude that insulin resistance in peripheral tissues in obese subjects with and without Type 2 diabetes may be partly explained by a reduced insulin mediated non-oxidative glucose metabolism and that this abnormality might be due to an absent insulin stimulation of glycogen synthase in skeletal muscles. This enzyme defect is correlated to obesity itself.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Diabetes Mellitus / enzymology*
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Fatty Acids, Nonesterified / blood
  • Female
  • Glucose Clamp Technique
  • Glycogen Synthase / metabolism*
  • Humans
  • Insulin / blood
  • Insulin Infusion Systems
  • Kinetics
  • Male
  • Middle Aged
  • Muscles / enzymology*
  • Obesity / enzymology*
  • Obesity / metabolism
  • Reference Values


  • Fatty Acids, Nonesterified
  • Insulin
  • Glycogen Synthase