Malin Steven K, Battillo Daniel J, Beeri Michal S, Mustapic Maja, Delgado-Peraza Francheska, Kapogiannis Dimitrios
Rutgers University, New Brunswick, New Jersey, USA.
Division of Endocrinology, Metabolism & Nutrition, Rutgers University, New Brunswick, New Jersey, USA.
Aging Cell. 2025 Jan;24(1):e14369. doi: 10.1111/acel.14369. Epub 2024 Oct 18.
Adults with prediabetes are at risk for Alzheimer's Disease and Related Dementia (ADRD). While exercise may lower ADRD risk, the exact mechanism is unclear. We tested the hypothesis that short-term exercise would raise neuronal insulin signaling and pro-BDNF in neuronal extracellular vesicles (nEVs) in prediabetes. Twenty-one older adults (18F, 60.0 ± 8.6 yrs.; BMI: 33.5 ± 1.1 kg/m) with prediabetes (ADA criteria; 75 g OGTT) were randomized to 12 supervised work-matched continuous (n = 13, 70% HR) or interval (n = 8, 90% HR and 50% HR for 3 min each) sessions over 2-wks for 60 min/d. Aerobic fitness (VOpeak) and body weight were assessed. After an overnight fast, whole-body glucose tolerance (total area under the curve, tAUC) and insulin sensitivity (SIis) were determined from a 120 min 75 g OGTT. nEVs were acquired from 0 and 60 min time-points of the OGTT, and levels of insulin signaling proteins (i.e., p-IRS-1, total-/p-Akt, pERK1/2, pJNK1/2, and pp38) and pro-BNDF were measured. OGTT stimulatory effects were calculated from protein differences (i.e., OGTT 60-0 min). Adults were collapsed into a single group as exercise intensity did not affect nEV outcomes. Exercise raised VOpeak (+1.4 ± 2.0 mL/kg/min, p = 0.008) and insulin sensitivity (p = 0.01) as well as decreased weight (-0.4 ± 0.9 kg, p = 0.04) and whole-body glucose tAUC (p = 0.02). Training lowered 0-min pro-BDNF (704.1 ± 1019.0 vs. 414.5 ± 533.5, p = 0.04) and increased OGTT-stimulated tAkt (-51.8 ± 147.2 vs. 95 ± 204.5 a.u., p = 0.01), which was paralleled by reduced pAkt/tAkt at 60 min of the OGTT (1.3 ± 0.2 vs. 1.2 ± 0.1 a.u., p = 0.04). Thus, 2 weeks of exercise altered neuronal insulin signaling responses to glucose ingestion and lowered pro-BNDF among adults with prediabetes, thereby potentially lowering ADRD risk.
患有糖尿病前期的成年人有患阿尔茨海默病及相关痴呆症（ADRD）的风险。虽然运动可能会降低ADRD风险，但其确切机制尚不清楚。我们测试了这样一个假设：短期运动能提高糖尿病前期患者神经元细胞外囊泡（nEVs）中的神经元胰岛素信号传导和前脑源性神经营养因子（pro-BDNF）水平。21名患有糖尿病前期（符合美国糖尿病协会标准；75克口服葡萄糖耐量试验）的老年人（18名女性，年龄60.0±8.6岁；体重指数：33.5±1.1千克/平方米）被随机分为两组，在两周内，每天进行60分钟的有监督的与工作相匹配的持续运动（n = 13，心率储备的70%）或间歇运动（n = 8，分别为心率储备的90%和50%，各持续3分钟）。评估有氧适能（峰值摄氧量）和体重。经过一夜禁食后，通过120分钟的75克口服葡萄糖耐量试验测定全身葡萄糖耐量（曲线下总面积，tAUC）和胰岛素敏感性（SIis）。在口服葡萄糖耐量试验的0分钟和60分钟时间点采集nEVs，并测量胰岛素信号蛋白（即p-IRS-1、总Akt/p-Akt、pERK1/2、pJNK1/2和pp38）和pro-BDNF的水平。根据蛋白质差异（即口服葡萄糖耐量试验60 - 0分钟）计算口服葡萄糖耐量试验的刺激效应。由于运动强度不影响nEVs结果，所以将成年人合并为一个组。运动提高了峰值摄氧量（+1.4±2.0毫升/千克/分钟，p = 0.008）和胰岛素敏感性（p = 0.01），同时降低了体重（-0.4±0.9千克，p = 0.04）和全身葡萄糖tAUC（p = 0.02）。训练降低了0分钟时的pro-BDNF水平（704.1±1019.0对414.5±533.5，p = 0.04），并增加了口服葡萄糖耐量试验刺激后的tAkt水平（-51.8±147.2对95±204.5任意单位，p = 0.01），这与口服葡萄糖耐量试验60分钟时pAkt/tAkt的降低（1.3±0.2对1.2±0.1任意单位，p = 0.04）相平行。因此，为期2周的运动改变了糖尿病前期成年人神经元对葡萄糖摄入的胰岛素信号反应，并降低了pro-BDNF水平，从而有可能降低ADRD风险。
