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

This study investigated the effects of metformin on some glucose regulatory indices in high fat diet (HFD) fedmale Wistar rats exposed to room temperature and chronic intermittent cold stress (CICS). Thirty rats were randomly dividedinto 5 groups. Group 1(control) was maintained on standard rat chow while groups 2-5 were maintained on HFD for 8weeksrespectively 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 toCICS 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 obtainedand analysed for insulin, cortisol, and lipid profile using laboratory kits. Pancreatic β-cell function and insulin resistancewere estimated using the Homeostasis Model Assessment equations. It was observed that blood glucose reduced significantlyin groups 2-4 on day21 compared to day1 values. At day 21 post-treatment, insulin level and insulin resistance were increasedwhile cholesterol levels were reduced in all HFD groups compared to control. Cortisol was increased in group 2 but reducedin groups 3-4 compared to control. HDL was reduced in groups 2-3 while liver glycogen was increased in groups 2, 3 and 5compared to control. Beta cell function and muscle glycogen were increased while LDL and triglyceride were reduced ingroups 2-4 compared to control. In conclusion, metformin ameliorates high-fat diet (HFD) induced impairment of glucoseand lipid regulatory indices by facilitating an increase in the storage of glycogen in the liver and muscle. Chronic intermittentcold stress exposure in HFD rats does not ameliorate insulin resistance but reduces impaired glucose and lipid regulatoryindices likely through an increase in adaptive thermo-genic mechanisms. The actions of metformin in reducing stressfulstimulus and preventing pre-diabetes syndrome in HFD fed rats are augmented by exposure to chronic intermittent coldstress.