Partial Pancreatectomy in Adult Humans Does Not Provoke β-Cell Regeneration

Abstract

OBJECTIVE—β-Cell regeneration has been proposed as a possible treatment for diabetes, but the capacity for new β-cell formation in humans is yet unclear. In young rats, partial pancreatectomy prompts new β-cell formation to restore β-cell mass. We addressed the following questions: In adult humans: 1) Does partial pancreatectomy provoke new β-cell formation and increased β-cell mass? 2) Is β-cell turnover increased after partial pancreatectomy? RESEARCH DESIGN AND METHODS—Protocol 1: human pancreatic tissue was collected from 13 patients who underwent two consecutive partial pancreas resections, and markers of cell turnover were determined in both tissue samples, respectively. Protocol 2: pancreas volumes were determined from abdominal computer tomography scans, performed in 17 patients on two separate occasions after partial pancreatectomy. RESULTS—Protocol 1: fasting glucose concentrations increased significantly after the 50% pancreatectomy (P = 0.01), but the fractional β-cell area of the pancreas remained unchanged (P = 0.11). β-Cell proliferation, the overall replication index (Ki67 staining), and the percentage of duct cells expressing insulin were similar before and after the partial pancreatectomy. The overall frequency of apoptosis (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling) was slightly increased following the partial pancreatectomy (P = 0.02). Protocol 2: pancreatic volume was ∼50% reduced to 35.6 ± 2.6 ccm³ by the partial pancreatectomy. The total pancreatic volume was unchanged after an interval of 247 ± 160 days (35.4 ± 2.7 ccm³; P = 0.51). CONCLUSIONS—Unlike in rodents, a 50% pancreatectomy does not prompt β-cell regeneration in adult humans. This explains the high incidence of diabetes after pancreatic resections. Such differences in β-cell turnover between rodents and humans should be born in mind when evaluating new treatment options aiming to restore β-cell mass in patients with diabetes.