Determinants of insulin-stimulated skeletal muscle glycogen metabolism in man.

To examine factors which influence skeletal muscle glycogen synthesis in man, we related insulin sensitivity measured by euglycaemic insulin clamp in 43 healthy males to muscle glycogen synthase (GS) activity, GS protein content (Western blot), glycogen concentrations and fibre composition. Insulin increased muscle glycogen content (P < 0.05) and the change in glycogen content correlated with the GS protein content (r = 0.90, P = 0.01). GS protein concentration correlated inversely with age (r = -0.69, P = 0.04). Non-oxidative glucose disposal was inversely related to per cent type 2B fibres (r = -0.52, P < 0.05). The influence of age on these relationships was separately studied in young (n = 12, age = 26 +/- 2 years) and elderly (n = 15, age = 56 +/- 2 years) males. Insulin increased GS activity significantly only in young subjects (from 17.8 +/- 3.0 to 25.3 +/- 3.2 nmol mg protein-1 min-1; P = 0.015). GS activity and non-oxidative glucose disposal correlated in young (r = 0.69, P = 0.01) but not in the elderly (r = 0.064, P = 0.82) males, and this relationship was not influenced by the degree of obesity. In conclusion, muscle fibre type and GS activity are both determinants of muscle glycogen metabolism in healthy, normoglycaemic males. The close relationship between non-oxidative glucose metabolism and GS activity in young males is altered in ageing.