Pancreatic structure and glucose tolerance in a longitudinal study of experimental pancreatitis-induced diabetes

C. J. Yeo, J. A. Bastidas, R. E. Schmieg, S. Walfisch, N. F. Couse, J. L. Olson, D. K. Andersen, M. J. Zinner

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22 Scopus citations

Abstract

Chronic pancreatitis is associated with glucose intolerannce and resultant pancreatogenic diabetes. Using the canine pancreatic duct-ligated model of pancreatitis, we serially evaluated pancreatic histology and electron microscopy, tolerance to intravenous and oral glucose, and insulin response to glucose loading. Pancreatic duct ligation caused microscopic evidence of acute pancreatitis at 1 week, progressing to acinar loss and fibrosis consistent with chronic pancreatitis at time periods up to 6 months. The islets of Langerhans showed degranulation early and appeared to be structurally preserved late. Calculated K values indicated a progressive significant deterioration in intravenous glucose tolerance, falling significantly from 3.46 ± 0.23 basally to 1.51 ± 0.17 at 6 months after duct ligation (p < 0.0001). Oral glucose tolerance deteriorated significantly, with the integrated glucose response rising from 23.7 ± 1.2 g/dl · minute basally to 32.3 ± 2.8 g/dl · minute at 6 months after duct ligation (p < 0.05). Integrated insulin response to both intravenous and oral glucose deteriorated with pancreatitis. Pancreatitis-induced glucose tolerance is a consistent feature of this duct-ligated model. Glucose intolerance stabilizes between 4 and 6 months after duct ligation and is associated with pancreatic acinar fibrosis and pancreatic endocrine structural preservation. While the mechanism of altered glucose tolerance may involve mechanical, neural, humoral, or vascular events, our data clearly support the conclusion that pancreatic ductal stenosis with resultant pancreatic fibrosis and chronic pancreatitis is associated with abnormal islet responsiveness leading to circulating insulin deficiency and glucose intolerance, depsite histologic and ultrastructural evidence of intact islets of Langerhans.

Original languageEnglish (US)
Pages (from-to)150-158
Number of pages9
JournalAnnals of surgery
Volume210
Issue number2
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • Surgery

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    Yeo, C. J., Bastidas, J. A., Schmieg, R. E., Walfisch, S., Couse, N. F., Olson, J. L., Andersen, D. K., & Zinner, M. J. (1989). Pancreatic structure and glucose tolerance in a longitudinal study of experimental pancreatitis-induced diabetes. Annals of surgery, 210(2), 150-158. https://doi.org/10.1097/00000658-198908000-00003