AJP - Endocrinology and Metabolism, Vol 268, Issue 5 E839-E844, Copyright © 1995 by American Physiological Society
Brain serotonin depletion attenuates diabetogenic effects of streptozotocin
Y. F. Yang and M. T. Lin
Department of Physiology, National Cheng Kung University Medical College, Tainan City, Taiwan, Republic of China.
The diabetogenic effects of streptozotocin (STZ) were studied on blood
glucose, plasma insulin, feeding and drinking, body weight, islet
morphology, and hypothalamic serotonin (5-HT) release in vehicle-pretreated
rats and in rats pretreated with either intracerebroventricular injection
of 5,7-dihydroxytryptamine (5,7-DHT; a 5-HT nerve fiber depletor),
intraperitoneal injection of p-chlorophenylalanine (PCPA; a tryptophan
hydroxylase inhibitor), or intraperitoneal injection of p-chloroamphetamine
(PCA; a neurotoxin for 5-HT nerve fiber). At four days after STZ
administration, vehicle-treated rats displayed hyperglycemia, polydipsia,
polyphagia, decreased plasma insulin level, derangement of islet morphology
(few insulin cells, accumulation of glucagon cells), and elevated 5-HT
release in the hypothalamus. The above diabetogenic effects of STZ were
attenuated by brain serotonin depletion induced by 5,7-DHT, PCPA, or PCA.
Furthermore, the STZ-induced hyperglycemia or derangement of islet
morphology was attenuated by peripheral sympathectomy or adrenalectomy. It
is concluded that brain serotonin depletion attenuates diabetogenic effects
of STZ by reducing sympathetic efferent activity in rats.
