FASTING DOES NOT IMPAIR INSULIN-STIMULATED GLUCOSE-UPTAKE BUT ALTERS INTRACELLULAR GLUCOSE-METABOLISM IN CONSCIOUS RATS

Effects of 24-h and 48-h fasting on maximal insulin-stimulated whole-b ody and muscle glucose uptake, glycogen synthesis, and glycolysis were studied in conscious rats by combining the glucose clamp technique wi th tracer methods. Fasting decreased body weight and basal plasma gluc ose, plasma insulin, hepatic glucose output, and glucose clearance (P < 0.05 for all). However, maximal insulin-stimulated whole-body glucos e uptake, normalized to body weight, was almost identical in fed, 24-h fasted, and 48-h fasted rats (191 +/- 8, 185 +/- 14, and 182 +/- 5 mu mol . kg-1 . min-1, respectively; P > 0.7). Similarly, rates of insuli n-stimulated glucose uptake by four different skeletal muscles, estima ted by the 2-deoxyglucose injection technique, were not different amon g the three groups. In contrast to glucose uptake, insulin-stimulated whole-body glycolysis was decreased significantly after fasting (36% a fter 48 h fasting; P < 0.05), whereas insulin-stimulated whole-body gl ycogen synthesis was increased (44% after 48 h fasting; P < 0.05). In fed rats, glycolysis was the major pathway for glucose metabolism duri ng hyperinsulinemia, accounting for 60 +/- 5% of glucose uptake. This fraction was decreased significantly by fasting (P < 0.01), so that af ter a 48-h fast, glycolysis accounted for only 40 +/- 3% of insulin-st imulated glucose uptake and glycogen synthesis became predominant path way, accounting for 60 +/- 3% of whole-body glucose utilization. Whole -body patterns of glucose metabolism during hyperinsulinemia were para lleled by glucose metabolism in individual muscles. These data indicat e that fasting for up to 48 h in rats had no effect on insulin-stimula ted glucose disposal (whole body or muscle) but resulted in a change o f the primary metabolic path for insulin-stimulated glucose utilizatio n from glycolysis to glycogen synthesis.