title: Brain serotonin depletion attenuates diabetogenic effects of streptozotocin.
abstract: 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.
authors.affiliation: Department of Physiology, National Cheng Kung University Medical College, Tainan City, Taiwan, Republic of China.
authors.forename: Y F
authors.initials: YF
authors.lastname: Yang
authors.forename: M T
authors.initials: MT
authors.lastname: Lin
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000172:deficiency* / Q000378:metabolism; D010133:p-Chloroamphetamine / Q000494:pharmacology
chemical_list: D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D010133:p-Chloroamphetamine; D010134:Fenclonine; D004298:Dopamine