Marked Expansion of Exocrine and Endocrine Pancreas with Incretin Therapy in Humans with increased Exocrine Pancreas Dysplasia and the potential for Glucagon-producing Neuroendocrine Tumors
- Alexandra E Butler1,
- Martha Campbell-Thompson2,
- Tatyana Gurlo1,
- David W Dawson3,
- Mark Atkinson2 and
- Peter C Butler1
- 1Department of Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California
- 2College of Medicine, Departments of Pathology and Pediatrics, University of Florida, Gainesville, Florida 32610-0275.
- 3Department of Pathology and Laboratory Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California
- Corresponding author: Alexandra E. Butler, Email:
Controversy exists regarding the potential regenerative influences of incretin therapy on pancreatic β cells versus possible adverse pancreatic proliferative effects. Examination of pancreata from age matched organ donors with type 2 diabetes (DM) treated by incretin therapy (n=8) or other therapy (n=12) and non diabetic controls (n=14) reveals a ∼40% increased pancreatic mass in DM treated with incretin therapy with both increased exocrine cell proliferation (p<0.0001) and dysplasia (increased pancreatic intraepithelia neoplasia, p<0.01). Pancreas in DM treated with incretin therapy was notable for α cell hyperplasia and glucagon expressing microadenomas (3/8) and a neuroendocrine tumor. β cell mass was reduced by approximately 60% in those with DM, yet a 6 fold increase was observed in incretin treated subjects although diabetes persists. Endocrine cells co-staining for insulin and glucagon were increased in DM compared to non diabetic controls (p<0.05) and markedly further increased by incretin therapy (p<0.05). In conclusion, in humans, incretin therapy resulted in a marked expansion of the exocrine and endocrine pancreatic compartments, the former being accompanied by increased proliferation and dysplasia, the latter by α cell hyperplasia with the potential for evolution into neuroendocrine tumors.
- Received December 4, 2012.
- Accepted March 14, 2013.
- © 2013 by the American Diabetes Association.
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