title: Diabetes induction by total pancreatectomy in minipigs with simultaneous splenectomy: a feasible approach for advanced diabetes research.
abstract: Safe and reliable diabetes models are a key prerequisite for advanced preclinical studies on diabetes. Chemical induction is the standard model of diabetes in rodents and also widely used in large animal models of non-human primates and minipigs. However, uncertain efficacy, the potential of beta-cell regeneration, and relevant side effects are debatable aspects particularly in large animals. Therefore, we aimed to evaluate a surgical approach of total pancreatectomy combined with splenectomy for diabetes induction in an exploratory study in Goettingen minipigs.
  
  
  
  Total pancreatectomy was performed in Goettingen minipigs (n = 4) under general anesthesia and endotracheal intubation. Prior to surgery, a central venous line was established for drug application and blood sampling. After median laparotomy, splenectomy was performed and the lobular pancreas was carefully dissected with particular attention to the duodenal vascular arcade. Close monitoring of blood glucose was initiated immediately after surgery by standard glucometer measurement or continuous glucose monitoring systems (CGMS). Exogenous insulin was given by multiple daily subcutaneous (s.c.) injections or via insulin pump systems (CSII). Complete endogenous insulin deficiency was confirmed by intravenous glucose tolerance test (ivGTT) and measurement of c-peptide. For establishing a suitable regimen for diabetes management, the animals were followed for 4-6 weeks.
  
  
  
  Following pancreatectomy and splenectomy, the animals showed a quick recovery from surgery and initial analgetic medication and volume substitution could be terminated within 24 h. A rapid increase in blood glucose was observed immediately following pancreatectomy necessitating insulin therapy. The induced exocrine insufficiency did not cause any clinical symptoms. Complete insulin deficiency could be confirmed in all animals by determination of negative c-peptide during glucose challenge. The two regimen of insulin treatment (multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII)) were both feasible with respect to acceptable glycemic control whereas CSII was considerably advantageous in comfort and popularity for both animals and care takers.
  
  
  
  Surgical pancreatectomy in combination with splenectomy to facilitate access to the pancreas is a feasible model for efficient diabetes induction in minipigs. The procedure itself and postoperative animal care could be performed without complications in this exploratory study. Nevertheless, this approach requires well-equipped infrastructure, experienced and skilled surgeons and anesthesiologists and dedicated animal care takers. The impact of total pancreatectomy in combination with splenectomy on the digestive and immune system must be considered in the design and definition of end points of experimental diabetes and transplantation studies.
authors: Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors: Sophie
authors: S
authors: Heinke
authors: Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. Barbara.ludwig@uniklinikum-dresden.de.|Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden Faculty of Medicine, DZD-German Centre for Diabetes Research, Technische Universität Dresden, Dresden, Germany. Barbara.ludwig@uniklinikum-dresden.de.|Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany. Barbara.ludwig@uniklinikum-dresden.de.
authors: Barbara
authors: B
authors: Ludwig
authors: Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors: Undine
authors: U
authors: Schubert
authors: Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors: Janine
authors: J
authors: Schmid
authors: Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors: Thomas
authors: T
authors: Kiss
authors: Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden Faculty of Medicine, DZD-German Centre for Diabetes Research, Technische Universität Dresden, Dresden, Germany.
authors: Anja
authors: A
authors: Steffen
authors: Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden Faculty of Medicine, DZD-German Centre for Diabetes Research, Technische Universität Dresden, Dresden, Germany.|Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany.|Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London, UK.
authors: Stefan
authors: S
authors: Bornstein
authors: Department of Visceral-, Thoracic- and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors: Stefan
authors: S
authors: Ludwig
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D005260:Female; D005951:Glucose Tolerance Test / Q000379:methods; D007332:Insulin Infusion Systems; D050417:Insulin-Secreting Cells; D010180:Pancreatectomy / Q000379:methods; D013156:Splenectomy / Q000379:methods; D013552:Swine; D013556:Swine, Miniature; D014183:Transplantation, Heterologous / Q000379:methods
chemical_list: D001786:Blood Glucose
keywords: animal model; diabetes; pancreatectomy