Acyclovir alleviates insulin resistance via activating PKM1 in diabetic mice

Aims: Diabetes mellitus (DM) is a major global health threat characterized by insulin resistance. A new tactic to ameliorate insulin resistance, thereby reversing the exacerbation of DM, is urgently needed. The work is aiming to provide a new strategy for DM treatment as well as to identify new targets. Main methods: C57BL/6 N mice were raised with high-fat diet (HFD) and infused with streptozotocin (STZ) to induce diabetes. The blood glucose, serum insulin, blood lipid and oxidative stress were detected. In vitro insulin resistance model experiment has been made to examine the molecular mechanisms underlying anti-diabetic effect of potential active chemicals in human hepatocellular carcinoma cells (HepG2). Key findings: Acyclovir, an antiviral nucleotide analog, alleviates insulin resistance by reducing blood lipids as well as oxidative stress and elevating insulin sensitivity on diabetic mice, which is in accord with results in the insulin resistance model of HepG2 cells. Mechanically, acyclovir stimulates pyruvate kinase M1 (PKM1) directly to activate adenosine 5 '-monophosphate (AMP)-activated protein kinase (AMPK)/Sirtuin1 (SIRT1) signaling pathway, thus improving insulin resistance. Significance: The present study supports that acyclovir should be translated to remedy DM, and PKM1 might be a valuable target to develop new medicines.

Automated summary

This study found that the antiviral drug acyclovir can improve insulin resistance by reducing blood lipids and oxidative stress, and increasing insulin sensitivity. Mechanistically, acyclovir stimulates pyruvate kinase M1 (PKM1) to activate the AMPK/SIRT1 signaling pathway, which could be a valuable target for developing new medications.