Abstract
AIMS/HYPOTHESIS: Insulin resistance in obesity and type 2 diabetes is associated with elevated plasma branched-chain amino acid (BCAA) levels. Here, we examined whether the ability of insulin to clear plasma BCAAs and any influence of acute exercise or exercise training on this response are intact in obesity and type 2 diabetes. METHODS: In four case-control studies of participants with type 2 diabetes matched to glucose-tolerant individuals with obesity and lean individuals, who underwent hyperinsulinaemic-euglycaemic clamps, we examined the effect of insulin on plasma BCAAs (studies I-IV), with or without prior acute exercise (60 min, 70% V˙O2max ) (study II), and before and after 10 weeks of endurance exercise training (study III) or 8 weeks of high-intensity interval training (study IV). RESULTS: Insulin sensitivity was reduced in individuals with type 2 diabetes compared with individuals with obesity (study I-IV) and lean individuals (studies I and IV), and in individuals with obesity vs lean individuals (study I) (all p<0.05). Exercise training (studies III and IV) increased insulin sensitivity in all groups (all p<0.01). Plasma BCAAs were elevated in individuals with type 2 diabetes compared with individuals with obesity (studies I, III and IV) and lean individuals (studies I and IV) (all p<0.05). The ability of insulin to reduce plasma BCAAs was significantly attenuated in participants with type 2 diabetes compared with both lean individuals (studies I and IV) and individuals with obesity (studies I, II and IV) (all p<0.05). Acute exercise slightly reduced plasma BCAAs in both individuals with type 2 diabetes and individuals with obesity but did not potentiate insulin's ability to reduce plasma BCAAs (study II). Exercise training had no impact on fasting BCAAs and did not affect insulin's ability to reduce plasma BCAAs in any group (studies III and IV) or rescue the attenuated insulin suppression of plasma BCAAs in participants with type 2 diabetes. CONCLUSIONS/INTERPRETATION: Our results demonstrate that insulin's ability to suppress plasma BCAAs is impaired in type 2 diabetes but is intact in individuals with obesity. Although acute exercise reduces fasting BCAA levels, neither acute exercise nor exercise training affects insulin's ability to suppress plasma BCAAs in glucose-tolerant individuals with or without obesity or in individuals with type 2 diabetes.