Vanweert 2020 J Clin Endocrinol Metab

Vanweert F, de Ligt M, Hoeks J, Hesselink MKC, Schrauwen P, Phielix E (2020) Elevated plasma branched-chain amino acid levels correlate with type 2 diabetes-related metabolic disturbances. J Clin Endocrinol Metab 106:e1827-36.

» PMID: 33079174

Vanweert Froukje, de Ligt Maerlies, Hoeks Joris, Hesselink Matthijs K C, Schrauwen Patrick, Phielix Esther (2020) J Clin Endocrinol Metab

Abstract: Patients with type 2 diabetes (T2DM) have elevated plasma branched-chain amino acid levels (BCAA). The underlying cause is however not known. Low mitochondrial oxidation of BCAA could contribute to higher plasma BCAA levels.

We aimed to investigate ex vivo muscle mitochondrial oxidative capacity and in vivo BCAA oxidation measured by whole-body leucine oxidation rates in patients with T2DM, first-degree relatives (FDR) and control participants (CON) with overweight or obesity.

An observational, community-based study was conducted.

Fifteen patients with T2DM, thirteen FDR and seventeen CON were included (age between 40-70 years and BMI ranging from 27-35 kg/m²).

High-resolution respirometry was used to examine ex vivo mitochondrial oxidative capacity in permeabilized muscle fibers. A subgroup of five T2DM and five CON underwent hyperinsulinemic-euglycemic clamps combined with 1- 13C leucine-infusion to determine whole-body leucine oxidation.

Total BCAA levels were higher in patients with T2DM compared to CON, but not in FDR, and correlated negatively with muscle mitochondrial oxidative capacity (r = -0.44, p<0.001). Consistently, whole-body leucine oxidation rate was lower in patients with T2DM vs. CON under basal conditions (0.202 ± 0.049 vs. 0.275 ± 0.043 μmol kg^-1 min^-1, p<0.05) and tended to be lower during high insulin infusion (0.326 ± 0.024 vs. 0.382 ± 0.013 μmol kg^-1 min^-1, p=0.075).

In patients with T2DM, a compromised whole-body leucine oxidation rate supports our hypothesis that higher plasma BCAA levels may at least originate partly from a low mitochondrial oxidative capacity.

© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserve • Keywords: 1- 13C leucine oxidation, Branched-chain amino acids, First-degree relatives, Insulin resistance, Mitochondrial oxidative capacity, Type 2 diabetes • Bioblast editor: Plangger M • O2k-Network Lab: NL Maastricht Schrauwen P

Labels: MiParea: Respiration  Pathology: Diabetes 

Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N  HRR: Oxygraph-2k 

2020-10