Increased islet beta cell replication adjacent to intrapancreatic gastrinomas in humans

J. J. Meier, A. E. Butler, R. Galasso, R. A. Rizza, P. C. Butler

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49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2689-2696
Number of pages8
JournalDiabetologia
Volume49
Issue number11
DOIs
StatePublished - Nov 2006

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Keywords

  • Beta cell mass
  • Beta cell replication
  • Gastrinoma
  • Islet hyperplasia
  • Zollinger-Ellison syndrome

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Meier, J. J., Butler, A. E., Galasso, R., Rizza, R. A., & Butler, P. C. (2006). Increased islet beta cell replication adjacent to intrapancreatic gastrinomas in humans. Diabetologia, 49(11), 2689-2696. https://doi.org/10.1007/s00125-006-0410-5