Increased islet beta cell replication adjacent to intrapancreatic gastrinomas in humans

Diabetologia. 2006 Nov;49(11):2689-96. doi: 10.1007/s00125-006-0410-5. Epub 2006 Sep 23.

Abstract

Aims/hypothesis: Type 1 and type 2 diabetes are characterised by a beta cell deficit. Islet hyperplasia has been described in patients with Zollinger-Ellison syndrome secondary to gastrin-producing tumours (gastrinomas), and gastrin therapy has increased beta cell mass in rodents and human islets in vitro. In the present studies we addressed the following questions: (1) In pancreas specimens from gastrinoma cases, is the fractional beta cell area increased? (2) If so, is this restricted to tumour-adjacent islets or also present in tumour-distant islets? (3) Is new beta cell formation (beta cell replication and islet neogenesis) increased and beta cell apoptosis decreased in pancreas specimens from gastrinoma cases?

Methods: Pancreas was obtained at surgery from four patients with Zollinger-Ellison syndrome caused by pancreatic gastrinomas and 15 control subjects at autopsy.

Results: Islet fractional beta cell area (p<0.001), islet size (p<0.001) and beta cell replication (Ki67 staining) (p<0.05) were increased in islets adjacent to the tumours, but not in tumour-distant pancreas, compared with control subjects. We did not observe any differences in beta cell apoptosis or in the number of insulin-positive cells in ducts either adjacent to or distant from the tumour.

Conclusions/interpretation: One or more factors released by human gastrinomas increase beta cell replication in islets immediately adjacent to the tumour, but not in tumour-distant islets. While these findings demonstrate that adult human beta cells can be driven into the cell cycle, they caution against the therapeutic usefulness of gastrin, since islets located >1 cm away from the gastrinomas did not exhibit changes in beta cell turnover, despite markedly elevated systemic gastrin levels sufficient to cause severe gastrointestinal symptoms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Mass Index
  • Cell Division / physiology*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 2 / pathology
  • Gastrinoma / pathology*
  • Gastrinoma / surgery
  • Gastrins / blood
  • Humans
  • Insulin-Secreting Cells / pathology*
  • Insulin-Secreting Cells / physiology
  • Islets of Langerhans / pathology
  • Middle Aged
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery
  • Zollinger-Ellison Syndrome / pathology
  • Zollinger-Ellison Syndrome / surgery

Substances

  • Gastrins