Decreased insulin sensitivity and muscle enzyme activity in elderly subjects

Abstract

Skeletal muscle glycogen deposition, and the activation of muscle glycogen synthase and pyruvate dehydrogenase during a hyerinsulinaemic euglycaemic clamp have been measured in six young and six elderly males matched for body mass index, physical activity and diet. Clamp glucose requirement (insulin, 0.1 U kg-1 h-1) was significantly lower in the older subjects (8.0 .+-. 0.4 mg kg-1 min-1) than in younger subjects (10.5 .+-. 0.6 mg kg-1 min-1, P < 0.02). Although the older subjects had a 6.5% decrease in lean body mass, clamp glucose requirement expressed per unit of lean body mass was also significantly decreased in the older subjects (10.2 .+-. 0.5) vs. 12.4 .+-. 0.6 mg kg-1 min-1, P < 0.05). The increase in muscle glycogen with the clamp was decreased by 33% in the older subjects (elderly; 13.1 .+-. 1.3 mg g-1 protein, young: 19.6 .+-. 2.2 mg g-1 protein; P < 0.05), and was strongly correlated with clamp glucose requirement (r = 0.72, P < 0.01). Glucose-6-phosphate independent glycogen synthase activity increased significantly between fasting and the end of the clamps in both groups (P < 0.001), but was lower at the end of the clamp in the older subjects (P < 0.05). Glycogen synthase activity at the end of the clamp correlated with both clamp glucose requirement (r = 0.83, P < 0.01) and muscle glycogen deposition (r = 0.73, P < 0.01). Skeletal muscle pyruvate dehydrogenase activity increased significantly betwen fasting and end of clamp in the young subjects (P < 0.05) but not in the elderly males. Pyruvate dehydrogenase activity at the end of the clamp, however, did not differ between the two groups and was not related to clamp glucose requirement. Thus the impaired glucose handling of the elderly may be related to decreased insulin action on muscle and muscle enzymes.