Development of a Porcine Model of Type 1 Diabetes by Total Pancreatectomy and Establishment of a Glucose Tolerance Evaluation Method

Abstract

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. 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. 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. 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.