Induction of diabetes in nonhuman primates by means of temporary arterial embolization and selective arterial injection of streptozotocin.
OBJECTIVE
To develop and assess a technique for induction of C peptide-negative diabetes in adult nonhuman primates in preparation for preclinical investigation of type 1 diabetes treatments.


METHODS
First, temporary embolization of the hepatic and gastric arteries was performed in 14 adult nonhuman primates (six cynomolgus, five rhesus, and three pigtail macaques). After embolization was confirmed with angiography, streptozotocin was injected at a dose of 50-70 mg/kg into the celiac artery and branches supplying the pancreas. The macaques then were given intravenous injections of arginine and glucose, and blood levels of insulin and C peptide were measured with an enzyme-linked immunosorbent assay to determine whether diabetes had been induced.


RESULTS
All but one of the macaques developed persistent long-term C peptide-negative diabetes after the streptozotocin injection. One macaque did not develop diabetes after the initial injection and was given a second dose of streoptozotocin, which did induce diabetes. None of the macaques showed any symptoms of hepatic or renal injury, and only one died (of gastric dilatation 5 days after the procedure).


CONCLUSIONS
Streptozotocin injection after temporary embolization of the hepatic and gastric arteries is a safe and reproducible method for inducing C peptide-negative diabetes in adult nonhuman primates in preparation for preclinical investigation of type 1 diabetes treatments.
Tal
Michael G
MG
Department of Diagnostic Imaging, Yale University School of Medicine, PO Box 208042, New Haven, CT 06520-8042, USA. michael.tal@yale.edu
Hirshberg
Boaz
B
Neeman
Ziv
Z
Bunnell
David
D
Soleimanpour
S
S
Bacher
John
J
Patterson
Noelle
N
Chang
Richard
R
Harlan
David M
DM
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000209:etiology*; D004621:Embolization, Therapeutic; D007269:Injections, Intra-Arterial; D011323:Primates; D013311:Streptozocin / Q000008:administration & dosage; D013997:Time Factors
D013311:Streptozocin