Møller Pauline M, Kjøbsted Rasmus, Petersen Maria H, de Almeida Martin E, Pedersen Andreas J T, Wojtaszewski Jørgen F P, Højlund Kurt
Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Diabetologia. 2025 May 22. doi: 10.1007/s00125-025-06454-y.
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.
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% ) (study II), and before and after 10 weeks of endurance exercise training (study III) or 8 weeks of high-intensity interval training (study IV).
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.
目的/假设:肥胖和2型糖尿病中的胰岛素抵抗与血浆支链氨基酸(BCAA)水平升高有关。在此,我们研究了肥胖和2型糖尿病患者中胰岛素清除血浆BCAAs的能力以及急性运动或运动训练对该反应的任何影响是否仍然存在。
在四项病例对照研究中,2型糖尿病患者与糖耐量正常的肥胖个体和瘦个体相匹配,这些个体接受了高胰岛素-正常血糖钳夹试验,我们研究了胰岛素对血浆BCAAs的影响(研究I-IV),有无急性运动(60分钟,70% )(研究II),以及耐力运动训练10周前后(研究III)或高强度间歇训练8周前后(研究IV)。
与肥胖个体(研究I-IV)和瘦个体(研究I和IV)相比,2型糖尿病个体的胰岛素敏感性降低,与瘦个体相比,肥胖个体的胰岛素敏感性也降低(研究I)(所有p<0.05)。运动训练(研究III和IV)使所有组的胰岛素敏感性增加(所有p<0.01)。与肥胖个体(研究I、III和IV)和瘦个体(研究I和IV)相比,2型糖尿病个体的血浆BCAAs升高(所有p<0.05)。与瘦个体(研究I和IV)和肥胖个体(研究I、II和IV)相比,2型糖尿病参与者中胰岛素降低血浆BCAAs的能力显著减弱(所有p<0.05)。急性运动使2型糖尿病个体和肥胖个体的血浆BCAAs略有降低,但未增强胰岛素降低血浆BCAAs的能力(研究II)。运动训练对空腹BCAAs无影响,在任何组中均未影响胰岛素降低血浆BCAAs的能力(研究III和IV),也未挽救2型糖尿病参与者中胰岛素对血浆BCAAs抑制作用的减弱。
结论/解读:我们的结果表明,2型糖尿病患者中胰岛素抑制血浆BCAAs的能力受损,但肥胖个体中该能力仍然存在。尽管急性运动可降低空腹BCAA水平,但急性运动和运动训练均不影响糖耐量正常的肥胖或非肥胖个体或2型糖尿病个体中胰岛素抑制血浆BCAAs的能力。