蛋氨酸限制 (MR) 改善葡萄糖代谢。H19 是骨骼肌胰岛素敏感性和葡萄糖代谢的关键调节因子。因此，该研究旨在揭示H19在MR对骨骼肌葡萄糖代谢的潜在机制。老年小鼠被喂养MR饮食25周。小鼠胰岛β细胞系β-TC6细胞和小鼠肌母细胞系C2C12细胞被用来建立凋亡或胰岛素抵抗模型。我们发现MR增加了腺病毒-2 (Bcl-2) 表达，减少了Bcl-2相关X蛋白 (Bax)，剪切半胱氨酸特异性蛋白酶3 (Caspase-3) 在胰腺中的表达，并促进了β-TC6细胞的胰岛素分泌。同时，MR增加了H19的表达，insulin Receptor Substrate-1（IRS-1）/ insulin Receptor Substrate-2（IRS-2）值，蛋白激酶B（Akt）磷酸化，糖原合成酶激酶-3β（GSK3β）磷酸化，并且在腓肠肌中增加了hexokinase 2 (HK2)的表达，促进了C2C12细胞的葡萄糖摄取。但是这些结果在C2C12细胞中H19 knockedown 之后被逆转了。总之，MR可以减轻胰腺细胞凋亡，促进胰岛素分泌。MR通过H19 / IRS-1 / Akt路径增强了腓肠肌胰岛素依赖性的葡萄糖摄取和利用，从而改善HFD老年小鼠的血糖紊乱和胰岛素抵抗。

Methionine restriction (MR) improves glucose metabolism. In skeletal muscle, H19 is a key regulator of insulin sensitivity and glucose metabolism. Therefore, this study aims to reveal the underlying mechanism of H19 upon MR on glucose metabolism in skeletal muscle. Middle-aged mice were fed MR diet for 25 weeks. Mouse islets β cell line β-TC6 cells and mouse myoblast cell line C2C12 cells were used to establish the apoptosis or insulin resistance model. Our findings showed that MR increased B-cell lymphoma-2 (Bcl-2) expression, deceased Bcl-2 associated X protein (Bax), cleaved cysteinyl aspartate-specific proteinase-3 (Caspase-3) expression in pancreas, and promoted insulin secretion of β-TC6 cells. Meanwhile, MR increased H19 expression, insulin Receptor Substrate-1/insulin Receptor Substrate-2 (IRS-1/IRS-2) value, protein Kinase B (Akt) phosphorylation, glycogen synthase kinase-3β (GSK3β) phosphorylation, and hexokinase 2 (HK2) expression in gastrocnemius muscle and promoted glucose uptake in C2C12 cells. But these results were reversed after H19 knockdown in C2C12 cells. In conclusion, MR alleviates pancreatic apoptosis and promotes insulin secretion. And MR enhances gastrocnemius muscle insulin-dependent glucose uptake and utilization via the H19/IRS-1/Akt pathway, thereby ameliorating blood glucose disorders and insulin resistance in high-fat-diet (HFD) middle-aged mice.