در موش هاي صحرايي ATP بررسي تغييرات حساسيت به انسولين در پي گنادكتومي يك طرفه ، دو طرفه ، تجويز استراديول ، پروژستون و تستوسترون به همراه بازكننده يا مسدودكننده كانال هاي پتاسيم حساس به

Effects of uni- and bi-lateral gonadectomy and administration of estradiol, progesterone and testosterone with pancreatic Beta-cell KATP channels blocker or opener on insulin sensitivity in rats

Background and aim: The effects of sex steroid hormones on insulin secretion and sensitivity is important for related disorders treatment. Therefore, the main purpose of the present study was to clarify the effects of sex hormones on insulin sensitivity in rats. Due to the role of pancreatic p-cellsʹ ATP-sensitive K+ (KATP) channels in insulin secretion, the effects of the hormones on pancreatic KATP channels were also studied. Method: Diazoxide (30mg/kg/day) or verapamil (100mg/kg/day) were used as pancreatic Betaellsʹ KATP channels opener and blocker, respectively. Testosterone (50 mg/kg/day) as replacement dose in biorchiectomized rats and 10 mg/kg/day in intact male animals and progesterone (20 mg/kg/day) and estradiol (200 µg/kg/day) in female rats were also used. Male rats were divided into nine groups consisting of control, uni-and bi-orchiectomized, testosterone receiving biorchiectomized, testosterone receiving intact rats, diazoxide or verapamil and testosterone plus diazoxide or verapamil receiving animals. Female rats were divided into control, uni-and bi-ovariectomized, progesterone or estradiol receiving bi-ovariectomized and progesterone, estradiol, diazoxide or verapamil receiving and progesterone plus diazoxide or verapamil receiving animals. After 4 weeks, serum glucose and insulin were measured and insulin sensitivity (glucose/insulin ratio) was compared statistically between the groups. Results: In the male rats, bi-orchiectomy, and diazoxide or diazoxide plus testosterone treatments increased insulin sensitivity; but uniorchiectomy, testosterone, verapamil or testosterone plus verapamil treatments decreased insulin sensitivity. In the female rats, uni- and biovariectomy, progesterone, diazoxide or progesterone plus diazoxide or verapamil, treatments increased insulin sensitivity; but estradiol or verapamil treatments resulted in the decrease of insulin sensitivity. Conclusion: Testosterone and estradiol were insulin sensitivity reducers but ovariectomy, bi-orchiectomy and progesterone were insulin sensitivity enhancer in rats. Presumably testosterone was not contributed in closing or opening of pancreatic Beta-cell KATP channels but progesterone influenced insulin sensitivity by its inhibitory effect on pancreatic KATP channels.