title: Development of a porcine model of type 1 diabetes by total pancreatectomy and establishment of a glucose tolerance evaluation method.
abstract: OBJECTIVE
  To develop and evaluate the efficacy of diabetes-targeted cell therapies in humans, a reliable model in larger animals is highly desirable. This article reports the surgical technique of total pancreatectomy in pigs and the biochemical analysis of the characteristics of totally pancreatectomized pigs.
  
  
  METHODS
  Surgical total pancreatectomy was conducted in 23 pigs. Blood glucose, insulin, biochemistries, activity index, and intravenous glucose tolerance test (IVGTT) were examined to assess the pathophysiological profiles of diabetic pigs.
  
  
  RESULTS
  A total of 14 pigs successfully underwent total pancreatectomy without requiring biliary reconstruction and were analyzed in the present study. Activity index was decreased from day 5 on and the mean survival of totally pancreatectomized pigs was 7.6 +/- 2.7 days. No endogenous insulin secretion was confirmed in these pigs. Pigs which received total pancreatectomy demonstrated significantly higher levels of ketone bodies. IVGTT performed within 4 days after total pancreatectomy showed a spontaneous decrease in blood glucose levels despite an absence of endogenous insulin secretion. IVGTT on day 5 or later showed continued hyperglycemia in pigs with total pancreatectomy. Histological examination showed atrophy of hepatocytes and decreased glycogen storage in the liver and decreased mucus production of the small intestine.
  
  
  CONCLUSIONS
  This article describes a porcine model of diabetes created by total pancreatectomy and it analyzes the pathophysiological profiles in the animals. The present study has suggested that IVGTT on day 5 or later after total pancreatectomy is a reliable method to evaluate the efficacy of cell therapies.
authors.affiliation: Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Shikata-cho, Okayama, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Naoya
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Teru
authors.initials: T
authors.lastname: Okitsu
authors.forename: Chen
authors.initials: C
authors.lastname: Yong
authors.forename: Takuya
authors.initials: T
authors.lastname: Fukazawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kosaka
authors.forename: Michiki
authors.initials: M
authors.lastname: Narushima
authors.forename: Takashi
authors.initials: T
authors.lastname: Arata
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood; D001284:Atrophy; D001786:Blood Glucose / Q000032:analysis; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology; D003967:Diarrhea / Q000503:physiopathology; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007657:Ketone Bodies / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000378:metabolism; D010180:Pancreatectomy; D011188:Potassium / Q000097:blood; D013552:Swine
chemical_list: D001786:Blood Glucose; D007657:Ketone Bodies; D006003:Glycogen; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D011188:Potassium