Goettingen Minipigs (GMP): Comparison of Two Different Models for Inducing Diabetes

We compare two methods for inducing diabetes in Goettingen minipigs (GMP), in five with the beta cell toxin streptozotocin (STZ) and in five other GMP by total pancreatectomy (PE). Glucose homeostasis was assessed with the intravenous glucose-tolerance test (IVGTT) and continual monitoring of interstitial glucose levels. At conclusion of the observation period, the pancreata were examined histologically. Three non-diabetic GMP served as control group.The IVGTT revealed markedly diabetic profiles in both GMP groups. STZ-GMP were found to harbor residual C-peptides and scattered insulin-positive cells in the pancreas. PE-GMP survived the total pancreatectomy only with intensive postoperative care.Although both methods reliably induced diabetes in GMP, the PE-GMP clearly had more health problems and required a greater expenditure of time and resources. The PE-GMP model, however, was better at eliminating endogenous insulin and C-peptide than the STZ-GMP model.Neither the physiology of glucose metabolism [1,2] nor the pathophysiologies of types 1 and 2 diabetes mellitus [3-8] are fully understood. Among the promising methods for treating type 1 diabetes is the transplantation of isolated microencapsulated islets of Langerhans [9,10]; metabolic surgery is one of the recently introduced treatment options for type 2 diabetes [11,12]. Many open questions regarding experimental diabetes treatment modalities have been answered in studies using small animal diabetes models. Such studies, for example, have answered fundamental questions regarding the appropriate transplantation site for islets cells [13,14], the function of islets cell transplants in vivo [15,16], the recipient immune response to islets cell transplants [17], and regarding postoperative glucose homeostasis in the field of diabetes metabolism research [18]. As valuable as such studies are, however, questions regarding the feasibility of such concepts under preclinical conditions can only be answered in large ani