Intermittent fasting modulates glycated hemoglobin, serum insulin, and hexokinase in STZ-induced diabetic male Wistar rats

Intermittent fasting (IF) is a recent non-pharmacological treatment used to manage type 2 diabetes mellitus (T2DM). Nevertheless, its relative effectiveness compared with conventional pharmacotherapy and its effects on major glycolytic enzymes are not well documented. This study was therefore designed to investigate the effects of various IF regimes on selected glycemic indicators and hepatic hexokinase activity in streptozotocin (STZ)-induced diabetic Wistar rats. The Wistar rats were induced with Type 2 diabetes by administering fructose followed by one low-dose injection of STZ (35 mg/kg). The animals were randomly assigned to six groups (n=3), namely: non-diabetic control, untreated diabetic control, metformin-treated (30 mg/kg), and three IF regimen groups (8, 12, and 15 hours daily). Serum glycated hemoglobin (HbA1c), insulin, and hepatic hexokinase activity were tested after the intervention period. Group E (12-hour IF regimen) had the greatest metabolic changes, with a significant decrease in HbA1c (p<0.05), an increase in serum insulin levels near metformin, and the highest significant increase (p<0.05) in hepatic hexokinase activity compared to other IF regimens and the untreated diabetic control. The 15-hour IF was less effective. The general glycemic control of 12-hour IF was similar to that of metformin. A middle-range 12-hour intermittent fasting diet is effective in glycemic control, restoration of insulin levels, and hepatic hexokinase activity in STZ-induced diabetic rats. The findings indicate an ideal fasting period with maximum metabolic advantage, thereby confirming IF as a powerful non-pharmacological approach, possibly through mechanisms such as improved glycolysis and increased insulin sensitivity.