RT Journal Article
SR Electronic
T1 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
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP DB_121686
DO 10.2337/db12-1686
A1 Butler, Alexandra E
A1 Campbell-Thompson, Martha
A1 Gurlo, Tatyana
A1 Dawson, David W
A1 Atkinson, Mark
A1 Butler, Peter C
YR 2013
UL http://diabetes.diabetesjournals.org/content/early/2013/03/17/db12-1686.abstract
AB 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.