NIDDM subjects are characterized by impaired glucose tolerance and insulin resistance with respect to glucose metabolism. To examine whether the defect in glucose utilization extends to amino acid metabolism, 6 NIDDM subjects (64 ± 4 yr of age; ideal body weight of 107 ± 3%) and 7 control subjects (58 ± 4 yr of age; ideal body weight of 105 ± 2%) were studied with the euglycemic insulin clamp technique, in combination with [1-14C]leucine and indirect calorimetry. All subjects participated in two studies. In study 1, after 3 h of tracer equilibration, a 3-h insulin clamp (40 mU · m−2 · min−1) was performed to define the effect of insulin on leucine kinetics and glucose metabolism. In study 2, subjects received a repeat 3-h insulin clamp, and a balanced amino acid solution was infused to increase the plasma amino acid concentrations ∼ 2-fold to examine the effect of combined physiological hyperinsulinemia-hyperaminoacidemia on the rate of leucine and glucose disposal. Insulin-mediated total body glucose uptake was significantly reduced in NIDDM during both study 1 (5.6 ± 0.4 vs. 6.9 ± 0.6 mg · kg−1 · min−1 P < 0.01) and study 2 (5.2 ± 0.4 vs. 6.8 ± 0.6, P < 0.01). Basal plasma leucine (120 ± 10 vs. 123 ± 11 μM) and α-ketoisocaproic acid concentrations (28 ± 3 vs. 25 ± 2 μM) were similar in NIDDM and control subjects, respectively. In contrast, the basal plasma glucose concentration (8.9 ± 0.8 vs. 4.7 ± 0.2 μM) and the HbA1c (8.5 ± 0.2 vs. 5.7 ± 0.2%) were significantly increased in NIDDM (P < 0.01). In the postabsorptive state, endogenous leucine flux, leucine oxidation, and nonoxidative leucine disposal were similar in NIDDM and control subjects. When insulin was infused without amino acids (study 1), the decrement in plasma leucine (53 ± 5 vs. 48 ± 4 μM), endogenous leucine flux (13 ± 2 vs. 11 ± 1 μmol · m−2 · min−1), leucine oxidation (1.6 ± 0.2 vs. 1.3 ± 0.1 μmol · m−2 · min−1), and nonoxidative leucine disposal (10 ± 1 vs. 8 ± 1 μmol · m−2 · min−1) was comparable in both groups. During combined insulin and amino acid infusion (study 2), plasma leucine concentration (185 ± 20 vs. 190 ± 15 μM) rose similarly in NIDDM and control subjects. In NIDDM, the increment in leucine oxidation (9.0 ± 0.7 vs. 8.5 ± 0.6 μmol · m−2 · min−1) and nonoxidative leucine disposal (9.3 ± 0.7 vs. 10.5 ± 0.9 μmol · m−2 · min−1) was similar to that observed in control subjects; the decrement in endogenous leucine flux (22.3 ± 2.1 vs. 20.2 ±1.9 μmol · m−2 · min−1) was comparable in both groups. We conclude that 1) insulin-mediated glucose disposal is significantly impaired in NIDDM and 2) the effect of insulin on endogenous leucine flux (protein degradation), nonoxidative leucine disposal (protein synthesis), and leucine oxidation is similar in NIDDM and control subjects. These results indicate a clear-cut dissociation between the effect of insulin on glucose and protein metabolism in NIDDM.
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Original Articles|
December 01 1993
Different Sensitivity of Glucose and Amino Acid Metabolism to Insulin in NIDDM
Livo Luzi;
Livo Luzi
Diabetes Division, Department of Internal Medicine, University of Texas Health Science Center and Audie L. Murphy Veterans Administration Hospital
San Antonio, Texas
Department of Medicine, Radioactive and Stable Isotopes Laboratory, S. Raphael Scientific Institute, University of Milan
Milan, Italy
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Alexander S Petrides;
Alexander S Petrides
Diabetes Division, Department of Internal Medicine, University of Texas Health Science Center and Audie L. Murphy Veterans Administration Hospital
San Antonio, Texas
Department of Medicine, Radioactive and Stable Isotopes Laboratory, S. Raphael Scientific Institute, University of Milan
Milan, Italy
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Ralph A De Fronzo
Ralph A De Fronzo
Diabetes Division, Department of Internal Medicine, University of Texas Health Science Center and Audie L. Murphy Veterans Administration Hospital
San Antonio, Texas
Department of Medicine, Radioactive and Stable Isotopes Laboratory, S. Raphael Scientific Institute, University of Milan
Milan, Italy
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Address correspondence and reprint requests simultaneously to Dr. Livio Luzi, Department of Medicine, S. Raphael Scientific Institute, University of Milan, 20132 Milan, Italy; and Dr. Ralph A. De Fronzo, Diabetes Division, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284.
Diabetes 1993;42(12):1868–1877
Article history
Received:
February 22 1993
Revision Received:
July 22 1993
Accepted:
July 22 1993
PubMed:
8243833
Citation
Livo Luzi, Alexander S Petrides, Ralph A De Fronzo; Different Sensitivity of Glucose and Amino Acid Metabolism to Insulin in NIDDM. Diabetes 1 December 1993; 42 (12): 1868–1877. https://doi.org/10.2337/diab.42.12.1868
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