TY - JOUR
T1 - Differential effects of insulin resistance on leucine and glucose kinetics in obesity
AU - Caballero, Benjamin
AU - Wurtman, Richard J.
N1 - Funding Information:
From the Clinical Research Center. Massachwetts Institute of Technology, Cambridge, MA. Address reprint requests to Benjamin Caballero. MD. PhD, Division of Human Nut&ion, The Johns Hopkins University, 615 N Wolfe St, Room 2041, Baltimore, MD 21205. Supported by National Institutes of Health Grant No. MOI-RR-00088 and by the Centefro r Brain Sciences and Metabolism Charitable Trust. Copytight 0 1991 by WB. Saunders Cornpan\ 0026049519114001-0011$03.00/0
PY - 1991/1
Y1 - 1991/1
N2 - The effects of insulin resistance on glucose and amino acid metabolism were studied in obese nondiabetic women (body mass index [BMI], (32.8 ± 2) and in lean controls. Glucose disposal rate, hepatic glucose production, and leucine carbon flux and oxidation were simultaneously measured during the postabsorptive state and during euglycemic hyperinsulinemia, by means of primed, constant infusions of d-[6,6-2H2]glucose and l-[1-13C]leucine. Each subject participated in two insulin clamp studies on separate days, at infusion rates of 10 and 40 mU (m2 · min)-1, producing plasma insulin levels of 20 to 25 and 70 to 80 μU/mL, respectively. Fat-free mass (FFM) was calculated from underwater weighing measurements. Insulin-mediated glucose disposal rate was significantly slower in the obese group: 2.05 ± 0.05 versus 3.84 ± 0.18 mg (kg · min)-1 in controls during the 10-mU insulin clamp, and 3.80 ± 0.23 versus 9.16 ± 0.47 mg (kg · min)-1 during the 40-mU clamp. The insulin-induced decrease in plasma levels of branched chain amino acids was also significantly blunted in the obese group. Baseline leucine flux was similar in lean and obese subjects (78 ± 3 and 71 ± 2 μmol (kg · h)-1, respectively), and its decline in response to insulin infusion was also comparable (8% and 10% during the 10-mU/m2 clamp, and of 17% and 18% during the 40-mU/m2 clamp in lean and obese, respectively). Basal leucine carbon oxidation (from [13C]leucine and [13C]αketoisocaproate [α-KIC] plasma enrichments) was also similar in lean and obese, and did not change significantly with insulin infusion. A significant correlation (R2 = .93) was found in both groups between lean body mass and plasma levels of branched chain amino acids. These results indicate that the elevation in plasma branched chain amino acid levels commonly observed in obesity is not necessarily associated with an impaired insulin-mediated amino acid flux, and that other factors, such as body composition, may be also determinants of the hyperaminoacidemia of obesity.
AB - The effects of insulin resistance on glucose and amino acid metabolism were studied in obese nondiabetic women (body mass index [BMI], (32.8 ± 2) and in lean controls. Glucose disposal rate, hepatic glucose production, and leucine carbon flux and oxidation were simultaneously measured during the postabsorptive state and during euglycemic hyperinsulinemia, by means of primed, constant infusions of d-[6,6-2H2]glucose and l-[1-13C]leucine. Each subject participated in two insulin clamp studies on separate days, at infusion rates of 10 and 40 mU (m2 · min)-1, producing plasma insulin levels of 20 to 25 and 70 to 80 μU/mL, respectively. Fat-free mass (FFM) was calculated from underwater weighing measurements. Insulin-mediated glucose disposal rate was significantly slower in the obese group: 2.05 ± 0.05 versus 3.84 ± 0.18 mg (kg · min)-1 in controls during the 10-mU insulin clamp, and 3.80 ± 0.23 versus 9.16 ± 0.47 mg (kg · min)-1 during the 40-mU clamp. The insulin-induced decrease in plasma levels of branched chain amino acids was also significantly blunted in the obese group. Baseline leucine flux was similar in lean and obese subjects (78 ± 3 and 71 ± 2 μmol (kg · h)-1, respectively), and its decline in response to insulin infusion was also comparable (8% and 10% during the 10-mU/m2 clamp, and of 17% and 18% during the 40-mU/m2 clamp in lean and obese, respectively). Basal leucine carbon oxidation (from [13C]leucine and [13C]αketoisocaproate [α-KIC] plasma enrichments) was also similar in lean and obese, and did not change significantly with insulin infusion. A significant correlation (R2 = .93) was found in both groups between lean body mass and plasma levels of branched chain amino acids. These results indicate that the elevation in plasma branched chain amino acid levels commonly observed in obesity is not necessarily associated with an impaired insulin-mediated amino acid flux, and that other factors, such as body composition, may be also determinants of the hyperaminoacidemia of obesity.
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U2 - 10.1016/0026-0495(91)90192-Y
DO - 10.1016/0026-0495(91)90192-Y
M3 - Article
C2 - 1984571
AN - SCOPUS:0026003658
SN - 0026-0495
VL - 40
SP - 51
EP - 58
JO - Metabolism
JF - Metabolism
IS - 1
ER -