Tanday et al. examined variations in metabolic responses and pancreatic islets following the administration of streptozotocin (STZ) and hydrocortisone (HC) in male and female transgenic Glu^CreERT2/Rosa26-eYFP mice. Both male and female mice displayed STZ-induced hyperglycaemia, impaired glucose tolerance and reduced insulin concentrations. The metabolic effects of HC were also similar in the two sexes, leading to the classic rise in circulating insulin levels, indicative of insulin resistance.

Following HC administration, female mouse islets contained a higher proportion of α-cells compared with males. In all HC-treated mice, there were relatively comparable increases in β- and α-cell turnover rates, with female mice displaying a slight increase in HC-induced β-cell apoptosis susceptibility. Interestingly, healthy control female mice demonstrated an inherently higher rate of α- to β-cell transdifferentiation, which was reduced by HC treatment. Moreover, the number of glucagon-positive α-cells transitioning into insulin-positive β-cells increased in male STZ mice, but not in females.

In summary, while there were no overt sex-specific alterations in metabolic profiles in STZ or HC mice, subtle differences in pancreatic islet morphology underscore the influence of sex hormones on islets. These findings emphasise the importance of consideration when interpreting observations between male and female subjects.

Read the full article in Journal of Endocrinology 259 e230174