Artemether ameliorates type 1 diabetes mellitus by modulating glycolipid metabolism in skeletal muscle.

Abstract

Diabetes is a metabolic disorder involving disruptions in glucose and lipid homeostasis. Skeletal muscle, the primary organ responsible for insulin responsiveness, is crucial for regulating glucose and lipid metabolism. Modulating glucose and lipid metabolism within skeletal muscle to treat diabetes remains an active research area. Artemether, an anti-malarial agent, has significant anti-diabetic and lipid-lowering effects. A type 1 diabetes (T1D) mouse model was induced using streptozotocin. This study comprised three groups: wild-type controls, T1D mice, and T1D mice that received artemether for 8 weeks. Hypoglycemic efficacy was assessed by measuring fasting blood glucose and glycated hemoglobin A1c. Muscle fiber characteristics were analyzed using periodic acid-Schiff staining and immunofluorescence. Alterations in glucose, lipid, pyruvate, and fatty acid metabolism in skeletal muscle were analyzed using immunoblotting, immunofluorescence, and qPCR. In T1D mice, glucose glycolysis and pyruvate metabolism were impaired, whereas fatty acid uptake and use were enhanced. Artemether treatment inhibited pyruvate dehydrogenase kinase 4 activity and activated pyruvate dehydrogenase, promoting aerobic glucose metabolism and suppressing fatty acid metabolism in skeletal muscle. These findings suggest that artemether can alleviate symptoms in T1D mice by modulating glycolipid metabolism in skeletal muscle.