Association between Sleep Deprivation and Metformin Treatment on Pancreatic and Liver Function in Mice

Abstract

Metformin has been widely used as a therapeutic drug for hyperglycemia and diabetes. Sleep is a vital and restorative process that is necessary for the proper functioning of organs. Sleep deprivation can induce multi-organ injury, including damage to the pancreas and liver that may result in hyperglycemia and diabetes. We studied the role of metformin in reversing sleep deprivation-induced hyperglycemia and pancreatic and liver dysfunction in mice. Mice were kept in cages and fed water and food ad libitum. Mice were subjected to a cycle of 1-day sleep deprivation (7:00 am-7:00 pm) and 1-day sleep for 30 days (15 cycles). Metformin (100 or 300 mg/kg/day p.o.) was administered from 16th to 30th day. Animals were killed on day 31. The pancreatic function was analyzed by determining the levels of serum glucose, amylase (AMYL), and insulin. Inflammation of the pancreas and liver was investigated by studying the expression of iNOS and NFĸB, and levels of cytokines. Proteins involved in the GLUT2-PPARγ-pAMPK glycolytic pathway in the liver were analyzed to evaluate the anti-hyperglycemic role of metformin. Sleep deprivation increased blood glucose, AMYL, and GPT levels. Furthermore, it resulted in liver and pancreatic inflammation. However, compared with control, sleep deprivation decreased the levels of proteins involved in the GLUT2-PPARγ-pAMPK glycolytic pathway. Sleep deprivation plus metformin decreased blood glucose and GPT levels and pancreatic inflammation. However, the combination increased the levels of proteins involved in the GLUT2-PPARγ-pAMPK glycolytic pathway. In addition, metformin alone increased the levels of AMYL, as well as resulted in islet atrophy, edge irregularities, and disordered pancreatic acinar cells. Metformin attenuates hyperglycemia and reduces pancreatic and liver inflammation in sleep-deprived mice; however, it may cause pancreatic dysfunction.