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- Title
Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion-Induced Insulin Resistance.
- Authors
Harris, Lydia-Ann L. S.; Smith, Gordon I.; Patterson, Bruce W.; Ramaswamy, Raja S.; Okunade, Adewole L.; Kelly, Shannon C.; Porter, Lane C.; Klein, Samuel; Jun Yoshino; Mittendorfer, Bettina; Okunade, Adewole; Yoshino, Jun
- Abstract
Systemic hyperaminoacidemia, induced by either intravenous amino acid infusion or protein ingestion, reduces insulin-stimulated glucose disposal. Studies of mice suggest that the valine metabolite 3-hydroxyisobutyrate (3-HIB), fibroblast growth factor 21 (FGF21), adiponectin, and nonesterified fatty acids (NEFAs) may be involved in amino acid-mediated insulin resistance. We therefore measured in 30 women the rate of glucose disposal, and plasma 3-HIB, FGF21, adiponectin, and NEFA concentrations, under basal conditions and during a hyperinsulinemic-euglycemic clamp procedure (HECP), with and without concomitant ingestion of protein (n = 15) or an amount of leucine that matched the amount of protein (n = 15). We found that during the HECP without protein or leucine ingestion, the grand mean ± SEM plasma 3-HIB concentration decreased (from 35 ± 2 to 14 ± 1 µmol/L) and the grand median [quartiles] FGF21 concentration increased (from 178 [116, 217] to 509 [340, 648] pg/mL). Ingestion of protein, but not leucine, decreased insulin-stimulated glucose disposal (P < 0.05) and prevented both the HECP-mediated decrease in 3-HIB and increase in FGF21 concentration in plasma. Neither protein nor leucine ingestion altered plasma adiponectin or NEFA concentrations. These findings suggest that 3-HIB and FGF21 might be involved in protein-mediated insulin resistance in humans.
- Subjects
INSULIN resistance; DRUG resistance; HYPERINSULINISM; VALINE; METABOLITES; AMINO acids; BLOOD sugar; BUTYRIC acid; COMPARATIVE studies; FATTY acids; GROWTH factors; HYPOGLYCEMIC agents; INGESTION; INSULIN; LEUCINE; RESEARCH methodology; MEDICAL cooperation; DIETARY proteins; RESEARCH; HYDROXY acids; EVALUATION research; RANDOMIZED controlled trials; ADIPONECTIN; GLUCOSE clamp technique; PHARMACODYNAMICS
- Publication
Diabetes, 2017, Vol 66, Issue 7, p1871
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db16-1475