Protection by nicotinamide against streptozotocin-induced reduction in pancreatic TRH.
The concentration of thyrotrophin-releasing hormone (TRH) immunoreactivity was determined in pancreatic islets and acini in the rat. In addition, time-course changes in TRH in response to an iv injection of streptozotocin (65 mg/kg body weight) with or without nicotinamide (500 mg/kg body weight) were examined in the whole pancreas. Furthermore, pancreatic TRH was measured in diabetic rats treated with insulin for 3 weeks. The TRH concentration in rat islets was 42-fold higher than in exocrine glands, indicating that the majority of pancreatic TRH is of islet origin. The mean concentration of pancreatic TRH decreased to 60 and 65% of the respective control values at 4 and 7 h after administration of streptozotocin, respectively. AT 24 h, it fell to 10% of control values without significant changes in TRH levels in the hypothalamus and gastrointestinal tract. In contrast, no significant change in pancreatic TRH was noted in rats given combined treatment with streptozotocin and nicotinamide. The injection of streptozotocin alone resulted in severe hypoglycaemia at 7 h and hyperglycaemia at 24 h, whereas neither resulted from the combined treatment. Insulin therapy had no influence on the decreased TRH concentrations in the diabetic pancreas. These results suggest that TRH may be localized to the B cells of pancreatic islets, and that the marked reduction in TRH in diabetic pancreases is not a metabolic consequence of insulin deficiency.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D009536:Niacinamide; D013311:Streptozocin; D013973:Thyrotropin-Releasing Hormone