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

Kelin Li; Minghui Wang; Ruxia Wang; Xiaojuan Wang; Hongchao Jiao; Jingpeng Zhao; Yunlei Zhou; Haifang Li; Hai Lin

doi:10.1016/j.tjnut.2023.08.024

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

J Nutr. 2023 Oct;153(10):2878-2892. doi: 10.1016/j.tjnut.2023.08.024. Epub 2023 Aug 22.

Authors

Kelin Li¹, Minghui Wang¹, Ruxia Wang², Xiaojuan Wang¹, Hongchao Jiao¹, Jingpeng Zhao¹, Yunlei Zhou³, Haifang Li⁴, Hai Lin⁵

Affiliations

¹ College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, China.
² Institute of Biological Resources, Jiangxi Academy of Sciences, Nanchang, China.
³ College of Chemistry and Material Science, Shandong Agricultural University, Tai'an, China.
⁴ College of Life Sciences, Shandong Agricultural University, Tai'an, China.
⁵ College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, China. Electronic address: hailin@sdau.edu.cn.

PMID: 37611831
DOI: 10.1016/j.tjnut.2023.08.024

Abstract

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 μmol/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 μM) 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.

Keywords: AMPK; S-sulfhydration; chick; glucose uptake; hydrogen sulfide; muscle fiber.