Artemether ameliorates type 2 diabetic kidney disease by increasing mitochondrial pyruvate carrier content in db/db mice

摘要

Diabetic kidney disease (DKD), the leading cause of kidney failure, is characterized by albuminuria and renal hypertrophy. Metabolic alterations and mitochondrial dysfunction play critical roles in DKD initiation and progression. Artemether, a methyl ether derivative of artemisinin used for the treatment of malaria, has been identified as a putative candidate for treating diabetes, but its effect on DKD has not been studied. The goal of this study was to examine the effect of artemether on type 2 diabetic db/db mice. Our results show that artemether reduced urinary albumin excretion, prevented diabetic kidney hypertrophy, attenuated glomerular basement membrane and tubular basement membrane thickening, and ameliorated foot process effacement in type 2 diabetic db/db mice. Artemether also protected against hyperglycemia and improved diabetic symptoms. In addition, it increased serum insulin level and restored the normal ratio of insulin, glucagon, and somatostatin levels in islets. Specifically, artemether increased the respiratory exchange ratio and regulated mitochondrial function and the redox state in the kidney. In conclusion, this experiment confirmed the renal protection ability of artemether in DKD. The mechanisms of this effect might be associated with the ability of artemether to increase mitochondrial pyruvate carrier content.