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DOI: 10.1148/radiol.2301021413
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(Radiology 2004;230:163-168.)
© RSNA, 2004

Experimental Studies

Induction of Diabetes in Nonhuman Primates by Means of Temporary Arterial Embolization and Selective Arterial Injection of Streptozotocin1

Michael G. Tal, MD, Boaz Hirshberg, MD, Ziv Neeman, MD, David Bunnell, MD, S. Soleimanpour, MD, John Bacher, Noelle Patterson, Richard Chang, MD and David M. Harlan, MD

1 From the Department of Diagnostic Imaging, Yale University School of Medicine, PO Box 208042, New Haven, CT 06520-8042 (M.G.T.); and the Transplantation and Autoimmunity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (B.H., D.B., S.S., N.P., D.M.H.); Radiology Department, Warren Grant Magnuson Clinical Center (Z.N., R.C.); and Surgery Service, Veterinary Resources Program, Office of Research Services (J.B.), Department of Health and Human Services, National Institutes of Health, Bethesda, Md. From the 2002 RSNA scientific assembly. Received October 31, 2002; revision requested January 13, 2003; final revision received May 12; accepted May 20. Address correspondence to M.G.T. (e-mail: michael.tal@yale.edu).

PURPOSE: 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.

MATERIALS AND 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).

CONCLUSION: 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.

© RSNA, 2004

Index terms: Animals • Diabetes mellitus • Experimental study • Pancreas, interventional procedures, 770.1264 • Pancreas, transplantation