Hydrogen Sulfide Regulates Glucose Uptake in Skeletal Muscles via S-sulfhydration of AMPK in Muscle Fiber-type Dependent Way.

BACKGROUND: The effect of hydrogen sulfide (H2 S) on glucose homeostasis remains to be elucidated, especially in the state of insulin resistance.

OBJECTIVES: In the present study, we aimed to investigated the H2 S-regulated glucose uptake respectively in M. pectoralis major (PM) muscle (mainly consisted of fast-twitch glycolytic fibers) and M. biceps femoris (BF) muscle (mainly consisted of slow-twitch oxidative fibers) of chicken, which is a potential model of insulin resistance.

METHODS: Chicks were subjected to intraperitoneal injection of sodium hydrosulfide (NaHS, 50 μmol/kg BW/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 adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, AMPK S-sulfhydration and mitogen-activated protein kinase (MAPK) pathway induced by NaHS were detected.

RESULTS: NaHS enhanced glucose uptake and utilization of chicks (P < 0.05). In myoblasts from PM muscle, NaHS (100 μM) increased glucose uptake via activating AMPK S-sulfhydration, AMPK phosphorylation and AMPK/p38 MAPK pathway (P < 0.05). However, NaHS decreased glucose uptake in myoblasts from BF muscle through suppressing p38 MAPK pathway (P < 0.05). Moreover, NaHS increased S-sulfhydration and in turn the phosphorylation of AMPK (P < 0.05).

CONCLUSIONS: This study first reveals the role of H2 S in enhancing glucose uptake and utilization of chicks. The result suggests that NaHS involves in glucose uptake in skeletal muscle via a fiber-type dependent way. 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.