Plasma acylcarnitines during insulin stimulation in humans are reflective of age-related metabolic dysfunction.
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.
Department of Biomedical Sciences, 228 Irvine Hall, Ohio University, Athens, OH, 45701, USA; Diabetes Institute, Ohio University, Athens, OH, 45701, USA; Ohio Musculoskeletal and Neurological Institute, Ohio University, Athens, OH, 45701, USA. Electronic address: consitt@ohio.edu.
Leslie A
LA
Consitt
Duke Molecular Physiology Institute, Duke University, Durham, NC, 27704, USA; Department of Medicine, Duke University, Durham, NC, 27704, USA.
Timothy R
TR
Koves
Duke Molecular Physiology Institute, Duke University, Durham, NC, 27704, USA; Department of Medicine, Duke University, Durham, NC, 27704, USA; Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, 27704, USA.
Deborah M
DM
Muoio
Department of Biomedical Sciences, 228 Irvine Hall, Ohio University, Athens, OH, 45701, USA.
Masato
M
Nakazawa
Department of Internal Medicine, Emory University, Atlanta, GA, 30322, USA.
Christopher A
CA
Newton
Department of Kinesiology, Human Performance Laboratory, East Carolina University, Greenville, NC, 27858, USA; East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, 27858, USA.
Joseph A
JA
Houmard
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000378:metabolism; D000596:Amino Acids / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology; D010084:Oxidation-Reduction; D010766:Phosphorylation; D055815:Young Adult
D000596:Amino Acids; D007328:Insulin; C116917:acylcarnitine; D000103:Acetyl-CoA Carboxylase; D005947:Glucose; D002331:Carnitine
Acetyl-CoA carboxylase; Acylcarnitine; Aging; Amino acid; Human; Metabolism
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