A mathematical model reveals sex-specific changes in glucose and insulin tolerance during rat puberty and maturation

Aim To evaluate the effects of maturation and sex on glucose metabolism during glucose tolerance (GTT) and insulin tolerance tests (ITT) in young and adult male and female rats by using two different approaches – the conventional, which uses area under the curve and glucose curve, and mathematical modeling that identifies parameters necessary for determining the function that models glucose metabolism. Methods Male and female rats at 3.5 and 12 months of age underwent standard GTT and ITT after overnight fasting. The parameters were identified by using Mathematica-module NonlinearModelFit [ ] for experimentally obtained data. Results When data were statistically analyzed, both sexes and age groups had similar glucose and insulin tolerance. In the mathematical model of GTT, parameters describing the rate of glucose concentration increase G’(0) and decrease G’I multiplied with maturation, with a concomitant decrease in the time point (tmax, tI) of reaching maximum and minimum glucose concentration (Gmax, G0). The mathematical model of ITT for males was independent of age, unlike of that for females, which had increased G’(0) and G’I, and more quickly recovered from hypoglycemia after maturation. Conclusion The mathematical model revealed female susceptibility to large glucose excursions, which are better reflected by ITT in young animals and by GTT in adults