The effect of insulin on the disposal of intravenous glucose was examined employing the euglycemic insulin clamp technique in 24 normal subjects. When the plasma insulin concentration was raised by approximately 100 μU/ml, total glucose metabolism rose to 6.63 ± 0.38 mg/kg · min. Basal splanchnic (hepatic venous catheter technique) glucose production, 2.00 increased only slightly. These results suggest that the ability of higher doses of insulin to further stimulate glucose metabolism is primarily the result of increased glucose storage by peripheral tissues, most likely muscle. 0.15 ± mg/kg · min, reverted to a small net glucose uptake which averaged 0.33 mg/kg · min over the ensuing 2 h. This represented only 5% of the total glucose metabolized. In contrast, leg (femoral venous catheterization) glucose uptake rose from 1.18 ± 0.14 to 8.40 ± 1.06 mg/kg of leg wt. per min. If all muscles in the body respond similarly to those in the leg, muscle would account for 85% of the total glucose metabolism. To determine the relative contributions of glucose oxidation versus glucose storage by peripheral tissues following hyperinsulinemia, we performed euglycemic insulin clamp studies in combination with indirect calorimetry. Basal glucose oxidation, 1.21 ± 0.10 mg/kg min, rose to 2.28 ± 0.16 (P < 0.01), and this increase above baseline accounted for only 20% of the total glucose metabolized, 5.44 ± 0.38 mg/kg · min. Following insulin, glucose storage increased to 3.18 ± 0.34 mg/kg min and was responsible for 59% of the total glucose metabolized. These results indicate that the primary effect of insulin on muscle tissue is to enhance glucose storage, presumably as glycogen. When a higher degree of hyperinsulinemia (163 ± 19 μl/ml) was created while maintaining euglycemia, total glucose metabolism (7.99 ± 0.58) and glucose storage (5.30 ± 0.80) both increased (P < 0.01) compared with the lower dose insulin clamp study, but glucose oxidation (2.70 ± 0.16 mgμkg min)increased only slightly. These results suggest that the ability of higher doses of insulin to further stimulate glucose metabolism is primarily the result of increased glucose storage by peripheral tissues, most likely muscle.

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