Pancreatic duct replication is increased with obesity and type 2 diabetes in humans

A. E. Butler, R. Galasso, A. Matveyenko, R. A. Rizza, S. Dry, P. C. Butler

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Aims/hypothesis: In a high-fat-fed rat model of type 2 diabetes we noted increased exocrine duct replication. This is a predisposing factor for pancreatitis and pancreatic cancer, both of which are more common in type 2 diabetes. The aim of the study reported here was to establish if obesity and/or type 2 diabetes are associated with increased pancreatic ductal replication in humans. Methods: We obtained pancreas at autopsy from 45 humans, divided into four groups: lean (BMI <25 kg/m2); obese (BMI >27 kg/m 2); non-diabetic; and with type 2 diabetes. Pancreases were evaluated after immunostaining for the duct cell marker cytokeratin and Ki67 for replication. Results: We show for the first time that both obesity and type 2 diabetes in humans are associated with increased pancreatic ductal replication. Specifically, we report that (1) replication of pancreatic duct cells is increased tenfold by obesity, and (2) lean subjects with type 2 diabetes demonstrate a fourfold increase in replication of pancreatic duct cells compared with their lean non-diabetic controls. Conclusions/interpretation: Pancreatic duct cell replication is increased in humans in response to both obesity and type 2 diabetes, potentially providing a mechanism for the increased risk of pancreatitis and pancreatic cancer in those with obesity and/or type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalDiabetologia
Volume53
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • DPP-IV inhibitor
  • GLP-1
  • Obesity
  • Pancreatic cancer
  • Pancreatic ductal
  • Pancreatitis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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