INVOLVEMENT OF LIVER AND SKELETAL-MUSCLE IN SUCROSE-INDUCED INSULIN-RESISTANCE - DOSE-RESPONSE STUDIES

The ability of dietary sucrose to induce insulin resistance independen t of changes in body weight is controversial. In the present study mal e rats were fed a high-starch (ST) diet (starch 68% of total kcal) ad libitum for 2 wk and then were fed equicalorically either the ST diet or a high-sucrose (SU) diet (sucrose 68% of total kcal) for 8 wk. Eugl ycemic, hyperinsulinemic (0, 1.2, 4.1, 8, 15 mU.kg(-1) min(-)1 n = 6-8 /group per dose) clamps were then used to establish dose-response rela tionships for glucose kinetics and metabolism. Body weight (513 +/- 3 g) and composition were similar between groups after the 8-wk dietary period. Glucose infusion rates (GIR; mg.kg(-1).min(-1)) were significa ntly less in SU (0.9 +/- 0.3, 5.8 +/- 0.6, 14.8 +/- 1.3, and 18 +/- 1. 1) than in ST rats (4.1 +/- 0.9, 12.3 +/- 1.2, 22.6 +/- 1.5, and 25.9 +/- 1.8) at 1.2, 4.1, 8, and 15 mU.kg(-1) min(-1), respectively. Impai red suppression of endogenous glucose production accounted for 46, 43, 23, and 0% of the reduction in GIR in SU rats at 1.2, 4.1, 8, and 15 mU.kg(-1).min(-1), respectively. Despite basal hyperinsulinemia (38 +/ - 2 mu U/ml in SU vs. 26 +/- 2 mu U/ml in ST rats), liver phosphoenolp yruvate carboxykinase (PEPCK) activity was 50% higher in SU than in ST rats and remained elevated in SU rats (by 30-40%) at the two lower in sulin doses. No skeletal muscle glycogen accumulation occurred in SU r ats at any of the insulin doses, and glycogen synthase I activity was significantly lower in SU rats at the two highest insulin doses. Thus an SU diet has the capacity to induce hepatic and skeletal muscle insu lin resistance. This insulin resistance may in part be explained by el evated hepatic PEPCK activity and reduced skeletal muscle glycogen syn thesis.