Background: Diabetic foot ulcers (DFUs) are a severe complication of diabetes
mellitus, leading to chronic infections, amputations, and increased mortality despite
existing treatments. More effective therapeutics are urgently needed, and animal
models provide a critical platform for investigating the molecular mechanisms
underlying DFUs. Streptozotocin (STZ)—administered at a low dose to induce type 2
diabetes (T2D) and at a high dose to induce type 1 diabetes—is commonly used in
mice and rats in DFU research. Aim: The objective of this study is to highlight the
importance of including male and female rats in DFU research. Methods: Both male
and female Sprague–Dawley rats, 6–8 weeks old, were fed a high-fat diet for 9 weeks.
STZ (25 mg/kg intraperitoneally) was administered weekly from the 6th week to
induce T2D. Results: Female rats required a higher dose of STZ compared to male
rats. The induction of T2D correlated positively with weight gain, which was greater
in males than in females. Conclusion: The findings suggest that in addition to gender
and weight, other factors may influence the induction of T2D in rats. Most studies in
the literature do not use both sexes in DFU research. The distinct responses to STZ
and weight gain observed emphasize the need to include both sexes and employ
a more detailed approach in preclinical studies to enhance the understanding
of DFU wound healing and translate the findings into potential treatments.
Relevance for patients: The multifactorial effect on diabetes development, which
differs in males and females, suggests the need to consider etiological, physiological,
and demographic factors, such as body weight, gender, age, and body mass index,
in the prevention and treatment of diabetes. This will also help in planning the
individualized treatment for DFUs.
