Nicotinamide mononucleotide increases muscle insulin sensitivity in women with prediabetes

Studies in rodents have shown obesity and aging impair tissue nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. The availability of nicotinamide mononucleotide (NMN) is an important rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in 25 postmenopausal women with prediabetes who were overweight/obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic-clamp procedure, increased by 25±7% (P<0.01) in the NMN group, which was accompanied by an increase in insulin-stimulated phosphorylation of muscle AKT (P<0.01), whereas neither outcome changed after placebo treatment. Body composition (fat mass, fat-free mass, intra-abdominal fat, intrahepatic triglyceride content) and muscle mitochondrial respiratory capacity did not change after treatment with placebo or NMN. These results demonstrate NMN improves muscle insulin sensitivity in women with prediabetes who are overweight/obese, independent of changes in body composition or mitochondrial function.

啮齿类动物研究显示，肥胖与衰老会损伤组织烟酰胺腺嘌呤二核苷酸（nicotinamide adenine dinucleotide，NAD+）的生物合成，进而引发代谢功能障碍。烟酰胺单核苷酸（nicotinamide mononucleotide，NMN）的生物利用度是哺乳动物NAD+生物合成过程中的重要限速因素。本研究针对25名合并超重/肥胖的前驱糖尿病绝经后女性，开展了一项为期10周的随机、安慰剂对照、双盲临床试验，以评估补充NMN对其代谢功能的影响。通过高胰岛素-正葡萄糖钳夹实验评估的胰岛素刺激葡萄糖处置率，在NMN组中升高了25±7%（P<0.01），同时伴随肌肉AKT胰岛素刺激磷酸化水平的上升（P<0.01）；而安慰剂组的这两项指标均未发生显著变化。安慰剂组与NMN组的身体成分（脂肪量、无脂肪量、腹腔内脂肪含量、肝内甘油三酯含量）及肌肉线粒体呼吸容量均未发生改变。上述结果表明，NMN可改善合并超重/肥胖的前驱糖尿病女性的肌肉胰岛素敏感性，且该效应不受身体成分或线粒体功能变化的影响。