Differential effects of insulin resistance on leucine and glucose kinetics in obesity

Benjamin H Caballero, Richard J. Wurtman

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)51-58
Number of pages8
JournalMetabolism
Volume40
Issue number1
DOIs
StatePublished - 1991
Externally publishedYes

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Leucine
Insulin Resistance
Obesity
Insulin
Glucose
Branched Chain Amino Acids
Carbon Cycle
Amino Acids
Hyperinsulinism
Body Composition
Body Mass Index
Carbon
Fats
Liver

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Differential effects of insulin resistance on leucine and glucose kinetics in obesity. / Caballero, Benjamin H; Wurtman, Richard J.

In: Metabolism, Vol. 40, No. 1, 1991, p. 51-58.

Research output: Contribution to journalArticle

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abstract = "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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