Partial pancreatectomy in adult humans does not provoke β-cell regeneration

被引:122
作者
Menge, Bjoern A. [1 ]
Tannapfel, Andrea [2 ]
Belyaev, Orlin [3 ]
Drescher, Robert
Mueller, Christophe [3 ]
Uhl, Waldemar [3 ]
Schmidt, Wolfgang E. [1 ]
Meier, Juris J. [1 ]
机构
[1] Ruhr Univ Bochum, Dept Med 1, St Josef Hosp, D-44791 Bochum, Germany
[2] Ruhr Univ Bochum, Inst Pathol, Bochum, Germany
[3] Ruhr Univ Bochum, St Josef Hosp, Dept Surg, D-4630 Bochum, Germany
关键词
D O I
10.2337/db07-1294
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE-beta-Cell regeneration has been proposed as a possible treatment for diabetes, but the capacity for new beta-cell formation in humans is yet unclear. In young rats, partial pancreatectomy prompts new beta-cell formation to restore beta-cell mass. We addressed the following questions: In adult humans: 1) Does partial pancreatectomy provoke new beta-cell formation and increased beta-cell mass? 2) Is beta-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 P-cell area of the pancreas remained unchanged (P = 0.11). P-Cell proliferation, the overall replication index (K167 staining), and the percentage of duct cells expressmig 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 similar to 50% reduced to 35.6 +/- 2.6 ccm(3) 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 beta-cell regeneration in adult humans. This explains the high incidence of diabetes after pancreatic resections. Such differences in beta-cell turnover between rodents and humans should be born in mind when evaluating new treatment options aiming to restore beta-cell mass in patients with diabetes.
引用
收藏
页码:142 / 149
页数:8
相关论文
共 47 条
[1]   β-cell turnover -: Its assessment and implications [J].
Bonner-Weir, S .
DIABETES, 2001, 50 :S20-S24
[2]   New sources of pancreatic β-cells [J].
Bonner-Weir, S ;
Weir, GC .
NATURE BIOTECHNOLOGY, 2005, 23 (07) :857-861
[3]   A 2ND PATHWAY FOR REGENERATION OF ADULT EXOCRINE AND ENDOCRINE PANCREAS - A POSSIBLE RECAPITULATION OF EMBRYONIC-DEVELOPMENT [J].
BONNERWEIR, S ;
BAXTER, LA ;
SCHUPPIN, GT ;
SMITH, FE .
DIABETES, 1993, 42 (12) :1715-1720
[4]   Extra-insular beta cells associated with ductules are frequent in adult human pancreas [J].
Bouwens, L ;
Pipeleers, DG .
DIABETOLOGIA, 1998, 41 (06) :629-633
[5]  
BRUNNER JC, 1988, MISC CUR EPHEMERID N, V132, P243
[6]   β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes [J].
Butler, AE ;
Janson, J ;
Bonner-Weir, S ;
Ritzel, R ;
Rizza, RA ;
Butler, PC .
DIABETES, 2003, 52 (01) :102-110
[7]   Clinical features of 52 neonates with hyperinsulinism [J].
de Lonlay-Debeney, P ;
Poggi-Travert, F ;
Fournet, JC ;
Sempoux, C ;
Vici, CD ;
Brunelle, F ;
Touati, G ;
Rahier, J ;
Junien, C ;
Nihoul-Fékété, C ;
Robert, JJ ;
Saudubray, JM .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 340 (15) :1169-1175
[8]  
DELONLAYDEBENEY P, 2003, CLIN ENDOCRINOLOGY O, V58, P355
[9]   Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation [J].
Dor, Y ;
Brown, J ;
Martinez, OI ;
Melton, DA .
NATURE, 2004, 429 (6987) :41-46
[10]   Glucagon-like peptide-1 and the islet β-cell:: Augmentation of cell proliferation and inhibition of apoptosis [J].
Drucker, DJ .
ENDOCRINOLOGY, 2003, 144 (12) :5145-5148