Metformin Effects are Augmented by Chronic Intermittent Cold Stress in High Fat Diet Fed Male Wistar Rats

Summary: This study investigated the effects of metformin on some glucose regulatory indices in high fat diet (HFD) fed male Wistar rats exposed to room temperature and chronic intermittent cold stress (CICS). Thirty rats were randomly divided into 5 groups. Group 1(control) was maintained on standard rat chow while groups 2–5 were maintained on HFD for 8weeks respectively prior to experimental procedures. Control, group 2(HFD untreated) and group 3(HFD+metformin (250mg/kg) were exposed to room temperature while groups 4(HFD untreated+CICS) and 5(HFD+CICS+metformin) were exposed to CICS for 21days. Blood glucose was monitored before initial exposure to HFD and on days 1,7,14 and 21 respectively. Blood samples (5mls) were thereafter collected by cardiac puncture following light ether anaesthesia, serum was obtained and analysed for insulin, cortisol, and lipid profile using laboratory kits. Pancreatic β-cell function and insulin resistance were estimated using the Homeostasis Model Assessment equations. It was observed that blood glucose reduced significantly in groups 2-4 on day21 compared to day1 values. At day 21 post-treatment, insulin level and insulin resistance were increased while cholesterol levels were reduced in all HFD groups compared to control. Cortisol was increased in group 2 but reduced in groups 3-4 compared to control. HDL was reduced in groups 2-3 while liver glycogen was increased in groups 2, 3 and 5 compared to control. Beta cell function and muscle glycogen were increased while LDL and triglyceride were reduced in groups 2-4 compared to control. In conclusion, metformin ameliorates high-fat diet (HFD) induced impairment of glucose and lipid regulatory indices by facilitating an increase in the storage of glycogen in the liver and muscle. Chronic intermittent cold stress exposure in HFD rats does not ameliorate insulin resistance but reduces impaired glucose and lipid regulatory indices likely through an increase in adaptive thermo-genic mechanisms. The actions of metformin in reducing stressful stimulus and preventing pre-diabetes syndrome in HFD fed rats are augmented by exposure to chronic intermittent cold stress.

Keywords
Cold stress; Metformin; pancreatic beta cell function; high fat diet; glucose metabolism