Safe induction of diabetes by high-dose streptozotocin in pigs.
OBJECTIVE
Streptozotocin (STZ) has been widely used to induce diabetes in rodents and nonhuman primates, but it has been found difficult to achieve a completely diabetic state in pigs in the absence of detrimental side effects. As a result, pancreatectomy has been advocated in this species. We have investigated the effects of 2 dosages of STZ to safely induce diabetes in pigs.


METHODS
Three pigs received Zanosar STZ at 150 mg/kg (group 1). Four pigs received Zanosar STZ at 200 mg/kg (group 2). The levels of glucose, insulin, and C-peptide when (a) fasting, (b) 30 minutes after eating, and (c) during intravenous glucose tolerance tests (IVGTTs) were measured in all pigs for 4 weeks after STZ injection. To confirm how long the diabetic state can be maintained after induction with STZ, levels were measured for 20 weeks in group 2.


RESULTS
One to 4 weeks after STZ administration, in group 1 (150 mg/kg) pigs, insulin and C-peptide levels were detected up to 7 microIU/mL and 0.4 ng/mL, respectively, both when fasting and after a meal test or IVGTT, indicating that the pigs had failed to become fully diabetic. In group 2 (200 mg/kg) pigs, insulin and C-peptide levels were less than the 2 microIU/mL and 0.25 ng/mL respective detection levels and did not increase after a meal test or IVGTT. Group 2 remained completely diabetic for the entire 20-week period of follow-up, without STZ-related hepatic or renal dysfunction.


CONCLUSIONS
High-dose (200 mg/kg) Zanosar STZ induces diabetes safely and completely in pigs without side effects. Pancreatectomy can, therefore, be avoided.
Hara
Hidetaka
H
Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
Lin
Yih Jyh
YJ
Zhu
Xiaocheng
X
Tai
Hao-Chih
HC
Ezzelarab
Mohamed
M
Balamurugan
A N
AN
Balamarugan
A N
AN
Bottino
Rita
R
Houser
Stuart L
SL
Cooper
David K C
DK
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002096:C-Peptide / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D010179:Pancreas / Q000473:pathology; D013311:Streptozocin / Q000008:administration & dosage*; D013552:Swine
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D013311:Streptozocin