Introduction & Objective: H2S is the third gaseous signaling molecule with a variety of biological effects.H2S may be involved in diabetes by modulating inflammation. The aim of this study was to determine the effects and mechanisms of H2S on high-fat diet-induced insulin resistance in skeletal muscle.
Methods: Mice were injected intraperitoneally with NaHS (50 μmol/kg/d ), the Sirt2 inhibitor AGK2 (1 mg/kg/d), or disulfiram (50 mg/kg/d). Body weight, IPGTT, ITT, calculation of skeletal muscle/body weight ratio, skeletal muscle muscle fiber cross sectional area and adipose tissue were detected. The effects of NaHS-induced sirt2 changes and the NLRP3/caspase-1/GSDMD pathway were detected.
Results: The SIRT2 inhibitor AGK2 accelerated blood glucose and body weight elevation and decreased skeletal muscle/body weight ratio in mice, and IPGTT and ITT indicated that AGK2 inhibited the recovery of blood glucose and exacerbated skeletal muscle atrophy and adiposity in mice.However, NaHS and disulfiram were effective in reversing the above changes.
Conclusion: H2S regulates skeletal muscle satellite cell proliferation and differentiation by activating sirt2 and thereby inhibiting NLRP3/caspase-1/GSDMD pathway-mediated skeletal muscle scorpioning, resulting in increased skeletal muscle mass and thus alleviating IR resistance.
K. Qiu: None. W. Kong: None.
