Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University , Shanghai , China.
Department of Biology, College of Arts and Sciences, Boston University , Boston , MA , USA.
Arch Physiol Biochem. 2019 Dec;125(5):470-477. doi: 10.1080/13813455.2019.1638414. Epub 2019 Jul 10.
Skeletal muscle atrophy is a complication of diabetes, partially induced by nicotinamide adenine dinucleotide (NAD) deficiency. This study investigates the potential of nicotinamide (NAM) supplementation, a precursor of NAD, against muscle atrophy. Mice were separated into normal control group, normal control with NAM administration group, diabetic group, and diabetic mice with NAM administration group. Basic characteristics, muscle weight, maximal grip strength, and myofibers cross-sectional area were analysed. Markers reflecting muscle atrophy and hypertrophy, and transforming growth factor β1/Smad2 (TGF-β1/Smad2) pathway were examined. NAM did not influence body weight and blood glucose. In diabetic mice, NAM increased NAD level, rescued muscle weight and strength loss, and increased myofibers cross-sectional area. NAM inhibited MuRF1 and Atrogin1, while elevated phosphorylation of Akt. Overactivation of TGF-β1/Smad2 pathway was repressed by NAM. NAM ameliorated diabetic muscle atrophy by rebalancing protein anabolism and catabolism, probably through de-activation of TGF-β1/Smad2 signaling.
骨骼肌萎缩是糖尿病的一种并发症，部分由烟酰胺腺嘌呤二核苷酸 (NAD) 缺乏引起。本研究探讨了烟酰胺 (NAM) 补充作为 NAD 的前体对肌肉萎缩的潜在作用。将小鼠分为正常对照组、正常对照组加 NAM 处理组、糖尿病组和糖尿病小鼠加 NAM 处理组。分析了基本特征、肌肉重量、最大握力和肌纤维横截面积。检测了反映肌肉萎缩和肥大的标志物，以及转化生长因子 β1/Smad2 (TGF-β1/Smad2) 途径。NAM 对体重和血糖没有影响。在糖尿病小鼠中，NAM 增加了 NAD 水平，挽救了肌肉重量和力量的丧失，并增加了肌纤维横截面积。NAM 抑制了 MuRF1 和 Atrogin1，同时增加了 Akt 的磷酸化。NAM 通过抑制 TGF-β1/Smad2 信号通路的过度激活来改善糖尿病性肌肉萎缩。NAM 通过去激活 TGF-β1/Smad2 信号转导，重新平衡蛋白质的合成和分解代谢，从而改善糖尿病性肌肉萎缩。
