The endocrine function of heterotopic islets of Langerhans.

Abstract

AbstractIslets of Langerhans may be removed from the pancreatic environment and transferred as autografts to a heterotopic site such as the spleen or liver. The success of such grafts has been equated with normoglycemia but success in dogs has been variable. We have developed a model of canine islet autografting that entails total pancreatectomy, preparation of a pancreatic suspension by perfusion of the pancreatic duct with collagenase, and delivery of the autograft to the spleen by reflux through tributaries of the splenic vein. In this study, fasting insulin response to intravenous glucose (0.5 g/kg), tolbutamide (0.5 g), glucagon (1.0 mg), and arginine (460 mg/kg) was measured before and 3 weeks after intrasplenic islet autografts. The 5 animals studied achieved fasting normoglycemia immediately; therefore, they were successful grafts. The response to glucose, however, was distinctly abnormal with statistically different peripheral insulin levels at 1, 3, 5, and 10 minutes. The insulin response was graphed, the area under the curve determined, and the integrated response was only 20% of preoperative controls. This diminished insulin response was reflected in impaired glucose clearance with a K value of 1.95 ± 0.24 in grafted animals compared to 3.12 ± 0.74 in preoperative controls. Peak insulin responses, however, to tolbutamide (70.4% of normal), glucagon (85.4%), and arginine (94.7%) were not statistically different in grafted animals compared to controls. The disparity of beta cell response to these various secretagogues suggests significant alteration of beta cell function either as a consequence of heterotopic placement, grafting injury, or accommodation to reduced islet number. Comparison of these data with those obtained in other systems supports some sort of accommodation to explain these beta cell changes.