The effect of hyperglycemia, hyperinsulinemia, and route of glucose administration on glucose oxidation and glucose storage

The separate effects of hyperinsulinemia, hyperglycemia, and the route of glucose administration on total glucose metabolism, glucose oxidation, and glucose storage were examined in 19 healthy young volunteers by employing the glucose clamp technique in combination with indirect calorimetry. Following 2 hr of euglycemic hyperinsulinemia (plasma insulin ∼97μU/ml) created by intravenous insulin/glucose infusion, total glucose metabolism (6.08 ± 0.56 mg/kg. min), glucose oxidation ( 2.63 ± 0.26 mg 0.26 mg kg · min), and glucose storage (3.46 ± 0.42 mg/kg · min) all increased 2 to 3-fold over basal rates. When additional hyperinsulinemia (163 ± 19 μU/ml) was created while maintaining euglycemia, total glucose metabolism (8.87 ± 0.69) and glucose storage (6.06 ± 0.51) both increased significantly (p < 0.005 and 0.02, respectively), but the rise in glucose oxidation (2.96 ± 0.17) was small and insignificant. During combined hyperglycemia (214 mg/dl) and hyperinsulinemia (217 μU/ml), total glucose metabolism (16.21 ± 0.58 mg/kg · min) and glucose storage (13.05 ± 0.57 mg/kg · min) both increased significantly (p < 0.001) compared to the euglycemic hyperinsulinemic conditions but glucose oxidation (3.04 ± 0.16 mg/kg · min) failed to increase further. These results indicate that the body's ability to oxidize glucose becomes saturated within the physiologic range of plasma insulin and glucose concentrations. With further increases in plasma glucose and insulin levels, the increase in glucose metabolism is primarily accounted for by an increase in glucose storage. The route of glucose administration, oral versus intravenous, had no effect on glucose oxidation. Under conditions of prolonged (6 hrs) euglycemic hyperinsulinemia, glucose oxidation was not significantly different whether the glucose was given intravenously (3.14 ± 0.11 mg/kg · min) or orally (3.63 ± 0.17). Similarly, under comparable conditios of hyperglycemic hyperinsulinemia, glucose oxidation was not different in subjects receiving intravenous (3.60 ± 0.28 mg/kg · min) and oral (4.03 ± 0.13) glucose. However, under conditions of hyperglycemic hyperinsulinemia both total body glucose metabolism (22.91 ± 0.42 versus 19.66 ± 1.10 mg/kg · min, p < 0.02) and glucose storage (18.76 ± 0.47 versus 15.95 ± 1.17, p < 0.02) were significantly greater during oral versus intravenous glucose. The site of the increased glucose storage observed with oral glucose could not be located since hepatic and femoral venous catheterization was not performed.