17beta-Estradiol and/or progesterone protect from insulin resistance in STZ-induced diabetic rats.
Recent clinical and experimental evidences suggest that sex steroids protect from insulin resistance associated with diabetes. Therefore, we have assessed the influence of E2 and/or P4 on insulin sensitivity by euglicaemic-hyperinsulinaemic clamp in ovariectomized streptozotocin-induced diabetic rats, focusing on key proteins of insulin signaling in skeletal muscle. Although low plasma levels of E2 (days 6 and 11) increased Glut-4 plasma membrane content and subsequent improved insulin sensitivity, they could not fully reverse hyperglycaemia negative effects on p85alpha-IRS-1 association and IRS-1 content during 11 days. However, high plasma levels of E2 (day 16) could reverse hyperglycaemia effects not only on Glut-4 plasma membrane content but also on p85alpha-IRS-1 association and IRS-1 protein content level. In contrast, P4 treatment only improved insulin sensitivity when its plasma concentration was low (days 6 and 11) and its effects were not associated with any proteins study in this paper. The combined therapy had a synergic effect on insulin sensitivity when their plasma levels were low (day 6) or high (day 16), that could be associated with Glut-4 plasma membrane content modulation, p85alpha-IRS-1 association and IRS-1 amount. These new findings improve our understanding of biochemical basis of insulin resistance due to hyperglycaemia and could open up new possibilities of treatment in uncontrolled type 1 DM.
Ordóñez
P
P
Department of Functional Biology, Physiology Area, University of Oviedo, C/ Julián Clavería s/n 33006, Oviedo, Spain.
Moreno
M
M
Alonso
A
A
Llaneza
P
P
Díaz
F
F
González
C
C
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D004958:Estradiol / Q000627:therapeutic use*; D005260:Female; D015309:Glucose Clamp Technique; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D010052:Ovariectomy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011374:Progesterone / Q000627:therapeutic use*; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D021122:Protein Subunits; D011374:Progesterone; D004958:Estradiol; D019869:Phosphatidylinositol 3-Kinases