Streptozotocin dose-response curve in tilapia, a glucose-responsive teleost fish.
Streptozotocin (STZ) causes beta cell necrosis and insulin-dependent diabetes in many species. The specificity of this beta cell toxin relates to its structure as an alkylating agent with an attached glucose moiety. STZ uptake by rodent beta cells appears to be via the GLUT-2 glucose transporter. Teleost fish, in general, are severely glucose intolerant. The effects of STZ were examined in tilapia, a teleost fish with highly glucose-responsive islets. Fasted tilapia were given 0, 100, 150, 200, 250, 300, or 350 mg/kg STZ iv. Plasma glucose levels were followed for 72 h and the fish autopsied. Histological sections of islets were stained by immunoperoxidase for tilapia insulin. Severe hyperglycemia was seen in 20, 80, and 100% of fish receiving 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 whether beta cell necrosis and permanent hyperglycemia ensued. All fish died or were killed within 9 days because of severe hepatic failure characterized by hepatic necrosis, jaundice, and ascites; islet morphology was relatively normal suggesting, even in a glucose-sensitive species, that fish islets either do not take up STZ or are highly resistant to its "diabetogenic" effects. Tilapia may thus be a useful model to elucidate mechanisms of action of STZ. Furthermore, STZ may provide important insights into differences in glucose uptake and metabolism by mammalian and piscine beta cells.
Wright
J R
JR
Departments of Pathology, Izaak Walton Killam-Grace Health Centre, Halifax, Nova Scotia, B3J 3G9, Canada.
Abraham
C
C
Dickson
B C
BC
Yang
H
H
Morrison
C M
CM
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental; D004305:Dose-Response Relationship, Drug; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000737:chemistry / Q000187:drug effects; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D013311:Streptozocin / Q000008:administration & dosage* / Q000494:pharmacology; D017210:Tilapia / Q000097:blood* / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin