الفهرس 
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Abstract
The aim of the present work was to study the metabolic consequences of estrogen deficiency with diabetes and to evaluate the benefits gained by estradiol treatment alone and insulin treatment alone versus combination of these two hormonal therapies. This was carried out by investigating the fasting blood glucose, glycosylated hemoglobin, lipid profile, in vivo vascular reactivity and insulin signaling pathway protein genes.
Eighty adult female albino rats of local strain, weighing (200-250) grams each, were used in this work. The animals were classified into the following groups:
1. Sham-operated control group (n =10) (Shame C).
2. Overectomized control group (n=10) (C).
3. Diabetic group (n =10) (D).
4. Ovariectomized diabetic group (n =10) (OVR D)
5. Insulin treated diabetic group (n =10) (D I).
6. Insulin -treated ovariectomized diabetic group (n =10) (OVR D I)
7. Estradiol-Insulin- treated diabetic group (n =10)(D E I)
8. Estradiol-Insulin- treated ovariectomized diabetic group (n =10) (OVX DEI).
At the end of 12 weeks rats scarified and examined for:
4. Biochemical assessment for glycemic and lipid profile.
5. Examination of the in vivo vascular reactivity.
6. Biochemical assessment of insulin signaling pathway protein genes by reverse transcriptase polymerase chain reaction (RT-PCR) for the following genes IRS 1, IRS 2, AKT2/PBK &PI3K.
The results showed that diabetes cause marked hyperglycemia and Dyslipidemia in the form of significant elevation of plasma triglycerides, total cholesterol, LDL and decreased HDL level, moreover decreased (AKT2, IRS 1, IRS2 , PI3K ), Also significant decrease in heart rate, marked elevation of basal mean arterial blood pressure and decreased vascular reactivity towards vasodilators and vasoconstrictors drugs.
Ovariectomy as in group 2 resulted in increased tendency to hyperglycemia although still non diabetic. Also Lipid profile showed unfavorable changes in the form of significant elevation of plasma triglycerides, total cholesterol, LDL and decreased of HDL with decreased (AKT2, IRS 1, IRS2, PI3K). Also significant decreased in heart rate, marked elevation of basal mean arterial blood pressure and decreased vascular reactivity towards vasodilators and vasoconstrictors drugs.
Combination of estrogen deficiency with diabetes in ovariectomized diabetic group as in group 4 resulted in aggravations of all the above mentioned metabolic derangements and decreased vascular reactivity towards vasodilators and vasoconstrictors drugs. The worsening additive effect of estrogen deficiency to diabetes towards lipids and lipoproteins metabolism makes it mandatory for estrogen replacement therapy beside insulin for competent glycemic control and preventing the catastrophic consequences of dyslipidemia especially on the cardiovascular system in postmenopausal females.
Treating rats with Insulin alone as in group 5&6 decreased blood glucose level,. With raised (AKT2, IRS 1, IRS2, PI3K) however as their values were still significantly lower than control group.
Combination of both estradiol and insulin therapies as in group 7,8 found to lower blood glucose level , improved the dyslipidemic state and normalized (AKT2, IRS 1,IRS2 , PI3K ) as compared to untreated groups, also nearly normalized vascular reactivity towards vasodilators and vasoconstrictors drugs.