Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects

Abstract

Background: Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity.

Objective: To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans.

Methods: Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U) during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5) to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5). In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U) in association with the above BCAA infusion (N = 4) or under the same conditions without BCAA infusion (N = 3). Plasma glucose turnover was measured prior to and during insulin infusion.

Results: Insulin infusion completely suppressed the endogenous glucose production (EGP) across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05). Insulin infusion stimulated whole-body glucose disposal rate (GDR) across all groups. However, the increase (%) in GDR was not different [median (1st quartile - 3rd quartile)] between Control and BCAA in either the 40U ([199 (167-278) vs. 186 (94-308)] or 80 U ([491 (414-548) vs. 478 (409-857)] experiments (P > 0.05). Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P < 0.05) with no differences between Control and BCAA in either of the experiments (P > 0.05).

Conclusion: Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

Fig 1. Experimental design.

Infusion protocol depicting the “basal” and “hyperinsulinemic-euglycemic clamp” study periods described in the text. [6,6–²H₂]glucose, branched-chain amino acids (BCAA; i.e., BranchAmin), saline, insulin and glucose were infused as indicated; [BCAA], total branched-chain amino acids concentration.

Fig 2. Plasma glucose turnover.

Rates of endogenous glucose production (EGP) and whole-body glucose disposal (GDR) in the basal period (i.e., Basal) and following insulin infusion (i.e., Insulin). Insulin was infused at either 40 mU/m²/min in a control group (A) and a group with increased plasma branched-chain amino acid concentrations (B) or 80 mU/m²/min in a control group (C) and a group with increased plasma branched-chain amino acid concentrations (D). Boxes describe interquartile range (IQR; 1^st quartile—3^rd quartile) with the horizontal line in the box representing the median value. P values are for the comparison of the corresponding medians.

Fig 3. Insulin-stimulated changes in plasma glucose turnover.

Changes from the basal period in the rates of endogenous glucose production (EGP) and whole-body glucose disposal (GDR) as a result of the insulin infusion at either 40 mU/m²/min (A) or 80 mU/m²/min (B) in the control group (Control) and the group with the increased plasma branched-chain amino acid (BCAA) concentrations. Boxes describe interquartile range (IQR; 1^st quartile—3^rd quartile) with the horizontal line in the box representing the median value.