Received July 11, 2006
Revised August 29, 2006
Accepted after revision October 23, 2006

¹ Oviedo University

^* To whom correspondence should be addressed. E-mail: tinog{at}uniovi.es.

	Abstract

It has been reported that in streptozotocin (STZ)-induced diabetes hyperglycaemia leads to progressive insulin resistance on peripheral tissues. In this study, we tried to elucidate the effects of hyperglycaemia on insulin sensitivity and insulin signaling in ovariectomized diabetic rats. In addition, we attempted to demonstrate the role of 17-estradiol or progesterone on insulin sensitivity, focusing on its effects on key proteins of skeletal muscle, insulin receptor (IR) and Glut-4. Our results show that hyperglycaemia could modulate insulin signaling, at IR and Glut-4 level, in a different manner depending on exposure time. 17-estradiol and progesterone have different effects on insulin signaling. 17-estradiol treatment improves insulin sensitivity, but its action is depends on the exposure time and its plasma level. During the early period of treatment (days 6-11), this hormone counteracts the effects of hyperglycaemia downstream of IR, whereas during the second period of treatment (days 11-16) it may counteract the effects of hyperglycaemia by modulating IR relative tyrosine phosphorylation. By contrast, progesterone only improves insulin sensitivity during the first period of treatment (days 6-11) and this effect is not associated with changes in IR and Glut-4 content. Both hormones have a protective role in skeletal muscle against the effects of glucose toxicity, but their effects begin at different stages of treatment. These new findings improve our understanding of insulin resistance in type 1 DM and of the risk/benefit ratio when 17-estradiol and progesterone are used in oral contraceptives or hormonal replacement therapy taken by menopausal women with controlled type 1 DM.

Key Words: Diabetes, Oestrogen, Progesterone

This article has been cited by other articles:

				B. J. Yauger, P. Gorden, J. Park, E. Cochran, and P. Stratton Effect of Depot Medroxyprogesterone Acetate on Glucose Tolerance in Generalized Lipodystrophy Obstet. Gynecol., August 1, 2008; 112(2): 445 - 447. [Abstract] [Full Text] [PDF]