TY - JOUR
T1 - Streptozotocin dose-response curve in tilapia, a glucose-responsive teleost fish
AU - Wright, James R.
AU - Abraham, Cherrie
AU - Dickson, Brendan C.
AU - Yang, Hua
AU - Morrison, Carol M.
N1 - Funding Information:
The authors acknowledge financial support from the Canadian Diabetes Association (in honor of Marion C. Dill) and the IWK Children’s Hospital Foundation and the technical support of Heather Kearns, Colleen Pelley, Janet Tam, and Marlene Henry.
PY - 1999/6
Y1 - 1999/6
N2 - Streptozotocin (STZ) causes β cell necrosis and insulin-dependent diabetes in many species. The specificity of this β cell toxin relates to its structure as an alkylating agent with an attached glucose moiety. STZ uptake by rodent β 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 β cell necrosis. Another group of fish receiving the highest dose were followed longer to determine whether β 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 β cells.
AB - Streptozotocin (STZ) causes β cell necrosis and insulin-dependent diabetes in many species. The specificity of this β cell toxin relates to its structure as an alkylating agent with an attached glucose moiety. STZ uptake by rodent β 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 β cell necrosis. Another group of fish receiving the highest dose were followed longer to determine whether β 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 β cells.
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U2 - 10.1006/gcen.1999.7269
DO - 10.1006/gcen.1999.7269
M3 - Article
C2 - 10336831
AN - SCOPUS:0032995576
SN - 0016-6480
VL - 114
SP - 431
EP - 440
JO - General and Comparative Endocrinology
JF - General and Comparative Endocrinology
IS - 3
ER -