Context: It has been reported that in uncontrolled type 1 DM, hyperglycaemia leads to insulin resistance. Furthermore, recent data from human and animal studies suggest that, in female, sex steroids protect from this state characteristic of DM.

Methods: We have assessed the influence of 17b-estradiol and/or progesterone on insulin sensitivity by euglicemic-hyperinsulinemic clamp experiments in ovariectomized streptozotocin-induced diabetic rats, focusing on their effects on insulin receptor (IR) in skeletal muscle and adipose tissue. Five experimental groups, treated for 6, 11 and 16 days, were designed. Ovariectomized group treated with placebo (V) and ovariectomized STZ-induced diabetic groups treated with placebo (SV), 17b-estradiol (SE), porgesterone (SP) and 17b-estradiol and progesterone (SEP).

Results: Hyperglycaemia leads to insulin resistance throughtout the experimental period in SV rats. Although 17b-estradiol treatment (SE) always improves insulin sensitivity and progesterone treatment (SP) only improves this parameter at 6 and 11 days, 17b-estradiol plus progesterone treatment (SEP) shows the highest insulin sensitivity at 6 and 16 days. IR level is the highest at 6 and 16 days in SEP group in skeletal muscle, while in adipose tissue this parameter increase throught the experiment. However, in skeletal muscle of SE rats and in both tissues of SP rats, IR reached the maximun level at day 11.

Conclusions: This study demonstrates that the sinergic effect of 17b-estradiol and progesterone on insulin sensitivity is hormonal-, time and tissue dependent and it could open up new possibilities of treatment in uncontrolled type 1 DM.