Hyperglycemia compensates for diet-induced insulin resistance in liver andskeletal muscle of rats

High-fat and high-sucrose diets increase the contribution of gluconeogenesi s to glucose appearance (glc Ra) under basal conditions. They also reduce i nsulin suppression of glc Ra and insulin-stimulated muscle glycogen synthes is under euglycemic, hyperinsulinemic conditions. The purpose of the presen t study was to determine whether these impairments influence liver and musc le glycogen synthesis under hyperglycemic, hyperinsulinemic conditions. Mal e rats were fed a high-sucrose, high-fat, or low-fat, starch control diet f or either 1 (n = 5-7/group) or 5 wk (n = 5-6/group). Studies involved two 9 0-min periods. During the first, a basal period (BP), [6-H-3] glucose was i nfused. In the second, a hyperglycemic period (HP), [6-H-3] glucose, [6-C-1 4] glucose, and unlabeled glucose were infused. Plasma glucose (BP: 111.2 /- 1.5 mg/dl; HP: 172.3 +/- 1.5 mg/dl), insulin (BP: 2.5 +/- 0.2 ng/ml; HP: 4.9 +/- 0.3 ng/ml), and glucagon (BP: 81.8 +/- 1.6 ng/l; HP: 74.0 +/- 1.3 ng/l) concentrations were not significantly different among diet groups or with respect to time on diet. There were no significant differences among g roups in the glucose infusion rate (mg . kg(-1) . min(-1)) necessary to mai ntain arterial glucose concentrations at similar to 170 mg/dl (pooled avera ge: 6.4 +/- 0.8 at 1 wk; 6.4 +/- 0.7 at 5 wk), percent suppression of glc R -a (44.4 +/- 7.8% at 1 wk; 63.2 +/- 4.3% at 5 wk), tracer-estimated net liv er glycogen synthesis (7.8 +/- 1.3 mug.g liver(-1) . min(-1) at 1 wk; 10.5 +/- 2.2 mug . g liver(-1) . min(-1) at 5 wk), indirect pathway glycogen syn thesis (3.7 +/- 0.9 mug . g liver(-1) . min(-1) at 1 wk; 3.4 +/- 0.9 mug . g liver(-1) . min(-1) at 5 wk), or tracer-estimated net muscle glycogenesis (1.0 +/- 0.3 mug . g muscle(-1) . min(-1) at 1 wk; 1.6 +/- 0.3 mug . g mus cle(-1) . min(-1) at 5 wk). These data suggest that hyperglycemia compensat es for diet-induced insulin resistance in both liver and skeletal muscle.