The experimental protocols used in the present study were approved by the Institutional Animal Ethics Committee, and the Deanship of Scientific Research, and College of Pharmacy, Qassim University, Saudi Arabia [Approval ID 2020-CP-12] 10137-cavm-2020-1-3-I. Male Sprague–Dawley rats (aged 3 months) were divided into five groups (six rats per group): a control group (NC), diabetes control group (DC), continuous calorie restriction group (CCR), alternate day calorie restriction group (ALT), and a calorie restriction for 2 days group (PF). The control group received an intramuscular (IM) injection of a vehicle (0.5 % w/v carboxyl methyl cellulose sodium). Hyperglycemia was induced in the other groups by an IM injection of STZ (55 mg/kg). The development of hyperglycemia was confirmed by measuring the rats’ blood glucose levels (Accu-Chek Glucometer, Roche, Germany) after 72 h and on day 4 after the last injection. Rats with fasting blood glucose levels higher than 126 mg/dl were considered to be diabetic and used as subjects in further studies [17 (link)]. The four fasting protocols were started after six weeks (Figure 1).
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