Plasma acylcarnitines during insulin stimulation in humans are reflective of age-related metabolic dysfunction
- Duke Molecular Physiology Institute, Duke University, Durham, NC, 27704 (United States)
- Department of Biomedical Sciences, 228 Irvine Hall, Ohio University, Athens, OH, 45701 (United States)
- Department of Internal Medicine, Emory University, Atlanta, GA, 30322 (United States)
- Department of Kinesiology, Human Performance Laboratory, East Carolina University, Greenville, NC, 27858 (United States)
The purpose of this study was to determine if plasma acylcarnitine (AC) profiling is altered under hyperinsulinemic conditions as part of the aging process. Fifteen young, lean (19–29 years) and fifteen middle-to older-aged (57–82 years) individuals underwent a 2-hr euglycemic-hyperinsulinemic clamp. Plasma samples were obtained at baseline, 20 min, 50 min, and 120 min for analysis of AC species and amino acids. Skeletal muscle biopsies were performed after 60 min of insulin-stimulation for analysis of acetyl-CoA carboxylase (ACC) phosphorylation. Insulin infusion decreased the majority of plasma short-, medium-, and long-chain (SC, MC, and LC, respectively) AC. However, during the initial 50 min, a number of MC and LC AC species (C10, C10:1, C12:1, C14, C16, C16:1, C18) remained elevated in aged individuals compared to their younger counterparts indicating a lag in responsiveness. Additionally, the insulin-induced decline in skeletal muscle ACC phosphorylation was blunted in the aged compared to young individuals (−24% vs. −56%, P < 0.05). These data suggest that a desensitization to insulin during aging, possibly at the level of skeletal muscle ACC phosphorylation, results in a diminished ability to transition to glucose oxidation indicative of metabolic inflexibility. - Highlights: • Plasma acylcarnitine profiling reveals metabolic inflexibility in aged individuals. • Time course acylcarnitine profiling is critical to identify metabolic dysfunction. • Acetyl-CoA carboxylase phosphorylation status is related to metabolic dysfunction.
- OSTI ID:
- 22696671
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 479, Issue 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
EGLP-1 lowers body weight better than exendin-4 by reducing food intake and increasing basal energy expenditure in diet-induced obese mice
In vivo cardiac glucose metabolism in the high-fat fed mouse: Comparison of euglycemic–hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach