acyclovir and Insulin-Resistance

The global emergence of obesity as an epidemic has made fatty liver disease a public health problem in the Western world. The increased incidence of obesity has been paralleled by an increase in metabolic syndrome in the same cohort of patients. The net consequence of insulin resistance in a large majority of these obese individuals is hepatic steatosis, which over time in a proportion of these patients progresses to steatohepatitis and cirrhosis. Despite the increased awareness among physicians regarding its presence, the diagnostic process has been hampered by the lack of sensitive and specific population-based screening tests. Liver biopsy remains the gold standard for diagnosis as well as for grading and staging of the disease process but its precise role in the diagnostic conundrum continues to be debated.

Topics: Acyclovir; Comorbidity; Disease Progression; Fatty Liver; Hepatitis C; Humans; Incidence; Insulin Resistance; Iron Overload; Liver; Liver Function Tests; Prevalence; Ultrasonography

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.. 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).. 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.. The present study supports that acyclovir should be translated to remedy DM, and PKM1 might be a valuable target to develop new medicines.

Topics: Acyclovir; AMP-Activated Protein Kinases; Animals; Diabetes Mellitus, Experimental; Diet, High-Fat; Insulin; Insulin Resistance; Mice; Mice, Inbred C57BL; Pyruvate Kinase