Mechanism of hyperglycemia during experimental duodenal ulceration Induced by dulcerozine in rats

• Published in: Japanese Journal of Pharmacology Vol. 46; no. suppl; p. 290
• Main Authors: Kurebayashi, Voh-ichi, Ikeda, Takuya, Akashi, Akira, Osada, Yasuaki
• Format: Journal Article
• Language: English
• Published: The Japanese Pharmacological Society 1988
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)57712-5

A profound, dose-related increase in the serum glucose level was elicited by ulcerogenic doses of dulcerozine (100 and 300 mg/kg s.c.) in fasted rats. Dulcerozine also provoked a marked elevation in the level of serum corticosterone, which was abolished by either adrenalectomy or hypophysectomy, suggesting that this agent may stimulate the pituitary-adrenal system as a potent chemical stressor. The hyperglycemic response to dulcerozine was totally abolished by adrenalectomy and partially inhibited by hypophysectomy. Intraperitoneal pretreatment of rats with either phentolamine (1 and 3 mg/kg) or RX-781094 (1 and 3 mg/kg) dose-dependently inhibited dulcerozine-induced elevation in the serum level of glucose, but prazosin (1 and 3 mg/kg) or propranolol (1 and 3 mg/kg) pretreatment had little effect. These blocking agents were without significant effect on the stimulation of the corticosterone secretion by dulcerozine. Based on these findings, it might be expected that not only the corticosterone hypersecretion but also the suppression of the alpha-2 adrenoceptor-mediated insulin secretion probably due to the augmented release of epinephrine from adrenal medulla is responsible for dulcerozine-induced hyperglycemia. In addition, dulcerozine-induced duodenal ulceration was significantly but not completely suppressed in adrenalectomized animals, although the mortality was rather increased. It seems therefore likely that the deleterious action of dulcerozine on the pituitary-adrenal system may contribute, at least in part, to its duodenal ulcerogenic property.