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Diabetes. 2017 Jul;66(7):1871-1878. doi: 10.2337/db16-1475. Epub 2017 May 4.

Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion-Induced Insulin Resistance.

Author information

1
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO.
2
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO mittendb@wustl.edu.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01538836 NCT01757340.

PMID:
28473464
PMCID:
PMC5482083
DOI:
10.2337/db16-1475
[Indexed for MEDLINE]
Free PMC Article

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