Effects of hyperprolactinaemia on glucose tolerance and insulin release in male and female rats

It has been shown that prolactin (PRL) induces glucose intolerance, hyperinsulinaemia and insulin resistance in several animal species, including rats. However, the sex differences regarding glucose homeostasis and insulin release in hyperprolactinaemic subjects have not been assessed to date. In the present study, hyperprolactinaemic (pituitary-grafted) or control (sham-operated) male and female rats were submitted to an i.v. glucose tolerance test (30 mg/100 g body weight, 30% glucose). Grafted female rats had fasting plasma glucose concentrations 26% above control (P < 0.01). After the glucose load there was a rapid and pronounced increase in plasma glucose levels in all animal groups, followed by a return to basal values within 30 min. However, the glucose concentrations in hyperprolactinaemic rats were significantly greater than those in controls at 5 min (males, P < 0.05) and 30 min (females, P < 0.05). The glucose disappearance rate was significantly increased in the grafted females compared with control (P < 0.01) and slightly increased in the grafted males. Plasma insulin concentration increased just after glucose load and returned to basal values within 5 min in all groups except for the grafted females, which had recovered their basal insulin levels at 15 min. The grafted male rats had insulin concentrations higher than those of sham-operated controls at 2 min (28.9 +/- 3.6 vs 17.3 +/- 2.1 microU/ml, P < 0.01), whereas females had plasma insulin concentrations greater than those in sham-operated controls 10 min after the glucose load (15.9 +/- 1.9 vs 10.1 +/- 1.4 microU/ml, P < 0.05). The areas under the plasma insulin concentration-time curves were also significantly increased in the hyperprolactinaemic rats and were positively correlated with plasma PRL concentrations (r = 0.613, P < 0.01). These results demonstrate that moderate chronic hyperprolactinaemia is associated with increased glucose-induced insulin release, which was altered at different times after the glucose load in grafted male and female rats, whereas fasting hyperglycaemia was observed only in grafted females, indicating a sexual dimorphism in the diabetogenic effects of PRL in rats.