Background
Exercise can ameliorate type II diabetes mellitus (T2DM) by regulating intestinal flora metabolites. However, the detailed mechanism needs to be further explored.
Conclusions
Exercise-mediated SCFAs-upregulation may ameliorate insulin resistance (IR) through increasing autophagy of skeletal muscle cells by binding to GPR43. This study provides a theoretical basis for targeting gut bacterial metabolites to prevent T2DM.
Methods
A T2DM model using mice was established by feeding them a high-fat diet and giving them subsequent streptozocin injections. Fasting blood glucose and serum insulin were determined by blood glucose meter and radioimmunoassay, respectively. Intestinal flora was measured by 16sRNA sequencing. SCFA content was measured by gas chromatography (GC) or enzyme-linked immunosorbent assay (ELISA). A fluorescently labeled 2-deoxyglucose (2-NBDG) kit was employed to detect glucose uptake capacity, and western blot was utilized to explore the signaling pathway of insulin resistance and cell autophagy.
Results
In the T2DM model, along with a reduction in insulin resistance (IR), exercise reversed the decline of intestinal Bacteroidetes and the increase of Firmicutes. For metabolites of Bacteroides, exercise restored the decline in total intestinal and plasma short-chain fatty acids (SCFAs) in T2DM mice. However, the administration of GLPG0974-the inhibitor of G protein-coupled receptor 43 (GPR43), which is the receptor of SCFAs-abolished exercise-mediated alleviation in IR in vivo and acetate-mediated reduction of skeletal muscle IR (SMIR) in vitro. Mechanistically, exercise induced skeletal muscle cell autophagy, thereby ameliorating SMIR, which was neutralized by GLPG0974 exposure. Conclusions: Exercise-mediated SCFAs-upregulation may ameliorate insulin resistance (IR) through increasing autophagy of skeletal muscle cells by binding to GPR43. This study provides a theoretical basis for targeting gut bacterial metabolites to prevent T2DM.