Insulin resistance in older rats.

Abstract

Insulin-stimulated glucose utilization was estimated in vivo in 1.5-, 4-, and 12-mo-old rats with an insulin suppression test wherein the height of the steady-state plasma glucose ( SSPG ) concentration, at similar steady-state plasma insulin levels, provides a direct reflection of the efficiency of insulin-stimulated glucose disposal. In parallel studies, the effect of age on in vitro insulin-stimulated glucose uptake was assessed in perfused hindlimb preparations. In addition, changes in the activity of enzymes that regulate muscle glycolysis, glycogenesis, and glycogenolysis were determined in isolated soleus muscle. The results indicated that rats got heavier as they became older, and changes in weight were associated with parallel increases in mean (+/- SE) SSPG concentrations as rats grew from 1.5 (56 +/- 3 mg/dl) to 4 (172 +/- 6 mg/dl) to 12 mo of age (194 +/- 8 mg/dl). The age-related decline in in vivo insulin action was associated with a reduction in insulin action on muscle, and maximal insulin-stimulated glucose uptake by perfused hindlimbs of 12-mo-old rats was approximately 50% of the value seen with perfused hindlimbs from 1.5-mo-old rats. Soleus muscle enzyme activity also varied with age, with significant increases in glycogen synthase and decreases in glycogen phosphorylase documented. Furthermore, muscle glycogen phosphorylase activity, which fell during an insulin infusion in 1.5-mo-old rats, did not change when 12-mo-old rats were infused at comparable insulin levels. Finally, glycogen content was significantly increased (P less than 0.01) in soleus muscle from 12-mo-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)