Insulin therapy has been suggested to preserve beta-cell mass in patients with diabetes through the mechanisms of beta-cell rest as well as direct effects on beta-cell proliferation. However, data about the effects of hyperinsulinism on beta-cell mass and turnover in humans are sparse. PATIENTS AND METHODS: Pancreatic tissue specimens from five patients with pancreatic insulinomas and ten non-diabetic control subjects were examined. Pancreatic sections were stained for insulin, Ki67 (replication) and TUNEL (apoptosis), and quantitative morphometric analyses were performed. RESULTS: Fractional beta-cell area was 1.11%±0.67% in the tumor-free pancreatic tissue of the insulinoma patients and 0.78%±0.26% in the control group (p=0.19). There also were no differences in islet size (p=0.62) or beta-cell nuclear diameter (p=0.20). Beta-cell replication and apoptosis were infrequently detected, without any measurable differences between the groups. There were also no differences in percentage of duct cells expressing insulin (p=0.47), a surrogate marker for islet neogenesis. CONCLUSIONS: Beta-cell area and turnover are not significantly altered in the proximity of intra-pancreatic insulinomas. Future in vivo studies, ideally employing larger animal models, are warranted to further evaluate the impact of exogenous insulin on beta-cell turnover.
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