Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects

N Engl J Med. 1996 Oct 31;335(18):1357-62. doi: 10.1056/NEJM199610313351804.


Background: Insulin resistance in the offspring of parents with non-insulin-dependent diabetes mellitus (NIDDM) is the best predictor of development of the disease and probably plays an important part in its pathogenesis. We studied the mechanism and degree to which exercise training improves insulin sensitivity in these subjects.

Methods: Ten adult children of parents with NIDDM and eight normal subjects were studied before starting an aerobic exercise-training program, after one session of exercise, and after six weeks of exercise. Insulin sensitivity was measured by the hyperglycemic-hyperinsulinemic clamp technique combined with indirect calorimetry, and the rate of glycogen synthesis in muscle and the intramuscular glucose-6-phosphate concentration were measured by carbon-13 and phosphorus-31 nuclear magnetic resonance spectroscopy, respectively.

Results: During the base-line study, the mean (+/-SE) rate of muscle glycogen synthesis was 63 +/- 9 percent lower in the offspring of diabetic parents than in the normal subjects (P < 0.001). The mean value increased 69 +/- 10 percent (P = 0.04) and 62 +/- 11 percent (P = 0.04) after the first exercise session and 102 +/- 11 percent (P = 0.02) and 97 +/- 9 percent (P = 0.008) after six weeks of exercise training in the offspring and the normal subjects, respectively. The increment in glucose-6-phosphate during hyperglycemic-hyperinsulinemic clamping was lower in the offspring than in the normal subjects (0.039 +/- 0.013 vs. 0.089 +/- 0.009 mmol per liter, P = 0.005), reflecting reduced glucose transport-phosphorylation, but this increment was normal in the offspring after the first exercise session and after exercise training. Basal and stimulated insulin secretion was higher in the offspring than the normal subjects and was not altered by the exercise training program.

Conclusions: Exercise increases insulin sensitivity in both normal subjects and the insulin-resistant offspring of diabetic parents because of a twofold increase in insulin-stimulated glycogen synthesis in muscle, due to an increase in insulin-stimulated glucose transport-phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Biological Transport, Active
  • Diabetes Mellitus, Type 2 / genetics
  • Exercise / physiology
  • Female
  • Glucose / metabolism*
  • Glucose Clamp Technique
  • Glucose-6-Phosphate / metabolism
  • Glycogen / biosynthesis*
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / physiology*
  • Insulin Secretion
  • Male
  • Muscle, Skeletal / metabolism*
  • Phosphorylation
  • Physical Fitness / physiology*


  • Insulin
  • Glucose-6-Phosphate
  • Glycogen
  • Glucose