Hydrogen Sulfide Regulates Glucose Uptake in Skeletal Muscles via S-Sulfhydration of AMPK in Muscle Fiber Type-Dependent Way

作者：Li, Kelin; Wang, Minghui; Wang, Ruxia; Wang, Xiaojuan; Jiao, Hongchao; Zhao, Jingpeng; Zhou, Yunlei; Li, Haifang; Lin, Hai^*

来源：Journal of Nutrition, 2023, 153(10): 2878-2892.

DOI：10.1016/j.tjnut.2023.08.024

• hydrogen sulfide
• glucose uptake
• AMPK
• S-sulfhydration
• muscle fiber
• chick

Background: The effect of hydrogen sulfide (H2S) on glucose homeostasis remains to be elucidated, especially in the state of insulin resistance.Objectives: In the present study, we aimed to investigate H2S-regulated glucose uptake in the M. pectoralis major (PM) muscle (which mainly consists of fast-twitch glycolytic fibers) and M. biceps femoris (BF) muscle (which mainly consists of slow-twitch oxidative fibers) of the chicken, a potential model of insulin resistance.Methods: Chicks were subjected to intraperitoneal injection of sodium hydrosulfide (NaHS, 50 mu mol/kg body mass/day) twice a day to explore glucose homeostasis. In vitro, myoblasts from PM and BF muscles were used to detect glucose uptake and utilization. Effects of AMP-activated protein kinase (AMPK) phosphorylation, AMPK S-sulfhydration, and mitogen-activated protein kinase (MAPK) pathway induction by NaHS were detected.Results: NaHS enhanced glucose uptake and utilization in chicks (P < 0.05). In myoblasts from PM muscle, NaHS (100 mu M) increased glucose uptake by activating AMPK S-sulfhydration, AMPK phosphorylation, and the AMPK/p38 MAPK pathway (P < 0.05). However, NaHS decreased glucose uptake in myoblasts from BF muscle by suppressing the p38 MAPK pathway (P < 0.05). Moreover, NaHS increased S-sulfhydration and, in turn, the phosphorylation of AMPK (P < 0.05).Conclusions: This study reveals the role of H2S in enhancing glucose uptake and utilization in chicks. The results suggest that NaHS is involved in glucose uptake in skeletal muscle in a fiber type-dependent way. The AMPK/p38 pathway and protein S-sulfhydration promote glucose uptake in fast-twitch glycolytic muscle fibers, which provides a muscle fiber-specific potential therapeutic target to ameliorate glucose metabolism.