The protective role of hydrogen sulfide from obesity-associated metabolic stress in GLP-1 regulation

Abstract

Circulating palmitic acid (PA) and glycated albumin (GA) are increased in obesity and cause metabolic stress leading to diabetes. This includes the impairment of the glucoregulatory hormone glucagon-like peptide-1 (GLP-1) secreted from intestinal L-cells. Recently, the gasotransmitter hydrogen sulfide (H2S) has been implicated in the enhancement of GLP-1 secretion. We hypothesized that H2S can reduce the oxidative stress caused by PA and GA, and play a protective role in L-cell function. In mouse and human L-cell models, PA and GA caused

an increase in reactive oxygen species (ROS). The H2S donor GYY4137 partially blocked PA- ROS induction. In mice, PA-enriched Western diet (WD) elevated body weight in both sexes and

elevated fasting blood glucose and lipid peroxidation in males. A single GYY4137 injection improved oral glucose tolerance in WD-fed male mice and also enhanced glucose-stimulated GLP-1 release. To conclude, H2S reduces oxidative stress in GLP-1 cells and can improve glucose clearance in mice.