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.

ABSTRACT: Controversy exists regarding the potential regenerative influences of incretin therapy on pancreatic ?-cells versus possible adverse pancreatic proliferative effects. Examination of pancreata from age-matched organ donors with type 2 diabetes mellitus (DM) treated by incretin therapy (n = 8) or other therapy (n = 12) and nondiabetic control subjects (n = 14) reveals an ?40% increased pancreatic mass in DM treated with incretin therapy, with both increased exocrine cell proliferation (P < 0.0001) and dysplasia (increased pancreatic intraepithelial neoplasia, P < 0.01). Pancreata in DM treated with incretin therapy were notable for ?-cell hyperplasia and glucagon-expressing microadenomas (3 of 8) and a neuroendocrine tumor. ?-Cell mass was reduced by ?60% in those with DM, yet a sixfold increase was observed in incretin-treated subjects, although DM persisted. Endocrine cells costaining for insulin and glucagon were increased in DM compared with non-DM control subjects (P < 0.05) and markedly further increased by incretin therapy (P < 0.05). In conclusion, incretin therapy in humans resulted in a marked expansion of the exocrine and endocrine pancreatic compartments, the former being accompanied by increased proliferation and dysplasia and the latter by ?-cell hyperplasia with the potential for evolution into neuroendocrine tumors.

SUBMITTER: Butler AE 

PROVIDER: S-EPMC3712065 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature