The Control of Hyperglycemia by Estriol and Progesterone in Alloxan induced Type I Diabetes Mellitus Mice Model through Hepatic Insulin Synthesis

As much as 20% of the women in menopause are reported to develop type I diabetes mellitus. The cessation of the ovarian syntheses of the female sex hormones is known to cause menopause in women, and the roles of estriol (one of the most abundant estrogens) and progesterone were investigated for hepatic insulin synthesis through estriol and progesterone induced synthesis of nitric oxide in the liver cells. Type 1 Diabetic mellitus mice were prepared by alloxan treatment, Nitric oxide was determined by methemoglobin method. Insulin was determined by enzyme linked immunosorbant assay. Injection of either 3.5 µM estriol or 3.5 nM progesterone to the diabetic mice which cannot synthesize pancreatic insulin, reduced the blood glucose level from 600 mg/dl to 120 mg/dl and 500 ± 25 mg/dl to 120 ± 6 mg/dl in 6 and 10 h respectively with simultaneous increase of the plasma insulin from 0 µunits/ml to 40 µunits/ml and 0 µunits/ml to 9.5 µunits/ml in the case of estriol and progesterone respectively with stimulated NO synthesis. The inhibition of the steroids induced NO synthesis by using NAME (NG-methyl-l-arginine acetate ester) in the reaction mixture resulted in the inhibition of hepatic insulin synthesis. Use of pure NO solution in 0.9% NaCl instead of either estriol or progesterone in the reaction mixture was found to stimulate the hepatic insulin synthesis. Both estriol and progesterone might be involved in the prevention of type 1 diabetes mellitus through the hepatic insulin synthesis even when the pancreatic insulin synthesis was impaired.