Streptozotocin dose-response curve in tilapia, a glucose-responsive teleost fish

Streptozotocin (STZ) causes beta cell necrosis and insulin-dependent diabet es in many species. The specificity of this beta cell toxin relates to its structure as an alkylating agent with an attached glucose moiety. STZ uptak e by rodent beta cells appears to be via the GLUT-2 glucose transporter. Te leost fish, in general, are severely glucose intolerant. The effects of STZ were examined in tilapia, a teleost fish with highly glucose-responsive is lets. Fasted tilapia were given 0, 100, 150, 200, 250, 300, or 350 mg/kg ST Z iv. Plasma glucose levels were followed for 72 h and the fish autopsied. Histological sections of islets were stained by immunoperoxidase for tilapi a insulin. Severe hyperglycemia was seen in 20, 80, and 100% of fish receiv ing 250, 300, and 350 mg/kg doses; however, sections of islets showed only partial degranulation with no evidence of beta cell necrosis. Another group of fish receiving the highest dose were followed longer to determine wheth er beta cell necrosis and permanent hyperglycemia ensued. All fish died or were killed within 9 days because of severe hepatic failure characterized b y hepatic necrosis, jaundice, and ascites; islet morphology was relatively normal suggesting, even in a glucose-sensitive species, that fish islets ei ther do not take up STZ or are highly resistant to its "diabetogenic" effec ts. Tilapia may thus be a useful model to elucidate mechanisms of action of STZ. Furthermore, STZ may provide important insights into differences in g lucose uptake and metabolism by mammalian and piscine beta cells. (C) 1999 Academic Press.