Regulation of whole-body leucine metabolism with insulin during mixed-meal absorption in normal and diabetic humans.

To determine the effects of insulin on dietary and endogenous leucine metabolism, five normal subjects, seven insulin-insufficient insulin-dependent (IDDM) diabetic patients, and five diabetic patients controlled with continuous subcutaneous insulin infusion (CSII) were studied before and for 8 h after ingestion of a chemically defined elemental test meal (10 cal/kg) containing crystalline amino acids. L-[1-14C]leucine was included in the meal to trace the entry and oxidation of the dietary leucine. Total (meal + endogenous) entry of leucine into the circulation was estimated with a constant infusion of [2H3]leucine. Postabsorptive and meal-related increases in the plasma leucine concentration were greater (P less than .05) in the insulin-insufficient IDDM than in the normal subjects but returned to near-normal values with CSII. Baseline leucine flux was approximately 40% greater in the insulin-insufficient IDDM than in normal subjects (2.17 +/- 0.17 vs. 1.55 +/- 0.15 mumol.kg-1.min-1, respectively; .05 less than P less than .01) but were near normal during CSII treatment (1.85 +/- 0.25 mumol.kg-1.min-1). Furthermore, total leucine entry during meal absorption was greater in the insulin-insufficient IDDM (1.41 +/- 0.10 mmol.kg-1.8 h-1) than in either normal (0.96 +/- 0.08 mmol.kg-1.8 h-1, P less than .01) or IDDM subjects during CSII treatment (1.09 +/- 0.11 mmol.kg-1.8 h-1, P less than .05). Fractional oxidation (approximately 40-50%) and entry of dietary leucine were similar in all three groups