Combined subtotal pancreatectomy with selective streptozotocin infusion--a model for the induction of insulin deficiency in dogs.

ABSTRACT

Standardized models of type I diabetes-like insulin deficiency in larger laboratory animals hardly exist. It was therefore investigated whether stable long-term insulin deficiency in dogs can be induced by selective beta-cell destruction in a safe and reliable procedure without damage of other organs. In Beagle dogs, the diabetogenic response to systemic streptozotocin administration (38.5-28 mg/kg b.wt.) was tested. In addition, resection of corpus and cauda pancreatis in combination with selective streptozotocin perfusion (25 mg/kg b.wt.) of the remaining pancreas tissue was evaluated. Whereas systemic streptozotocin administration failed to destroy insulin secretion, but led to a variety of intoxication symptoms even in comparatively low doses (28 mg/kg b.wt.), the latter procedure resulted in a complete and persistent insulin depletion (basal serum immunoreactive insulin less than or equal to 3 microU/ml, no stimulated response) without toxic organ damage or other serious side effects. The dogs developed type I-like diabetes, which required continuous exogenous insulin substitution. From these results, subtotal pancreatectomy with selective streptozotocin perfusion of the remaining pancreas is proposed as a safe model of insulin deficiency in dogs, which should be further evaluated in experimental diabetology.