In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD⁺) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a 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 postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT 03151239).

在啮齿动物中，肥胖和衰老会损害烟酰胺腺嘌呤二核苷酸 (NAD ⁺ ) 的生物合成，从而导致代谢功能障碍。烟酰胺单核苷酸 (NMN) 可用性是哺乳动物 NAD ⁺的限速因素生物合成。我们进行了一项为期 10 周的随机、安慰剂对照、双盲试验，以评估补充 NMN 对患有超重或肥胖的前驱糖尿病的绝经后妇女代谢功能的影响。通过使用高胰岛素-正常血糖钳夹评估胰岛素刺激的葡萄糖处理和骨骼肌胰岛素信号 [蛋白激酶 AKT 的磷酸化和雷帕霉素的机制靶标 (mTOR)] 在补充 NMN 后增加，但在安慰剂治疗后没有变化。 NMN 补充剂上调血小板衍生生长因子受体 β 和其他与肌肉重塑相关的基因的表达。这些结果表明，NMN 增加了超重或肥胖的糖尿病前期女性的肌肉胰岛素敏感性、胰岛素信号传导和重塑（clinicaltrial.gov NCT 03151239）。