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This Article Accepted manuscript (PDF) All Versions of this Article: EJE-08-0596v1 160/2/185    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Reers, C. Articles by Ritzel, R. Search for Related Content PubMed PubMed Citation Articles by Reers, C. Articles by Ritzel, R.

Impaired islet turnover in human donor pancreata with aging

C Reers, Department of Internal Medicine I, Division of Endocrinology and Diabetes, University of Heidelberg, Heidelberg, Germany
S Erbel, Department of Internal Medicine I, Division of Endocrinology and Diabetes, University of Heidelberg, Heidelberg, Germany
I Esposito, Institute of Pathology, University of Heidelberg, Heidelberg, Germany
B Schmied, Department of General Surgery, University of Heidelberg, Heidelberg, Germany
M Buechler, Department of General Surgery, University of Heidelberg, Heidelberg, Germany
P Nawroth, Department of Internal Medicine I, Division of Endocrinology and Diabetes, University of Heidelberg, Heidelberg, Germany
R Ritzel, Department of Internal Medicine I, Division of Endocrinology and Diabetes, University of Heidelberg, Heidelberg, Germany

Correspondence: Robert Ritzel, Email: robert.ritzel{at}med.uni-heidelberg.de

Abstract

Objective: The prevalence of type 2 diabetes mellitus escalates with aging although beta-cell mass, a primary parameter of beta-cell function, is subject to compensatory regulation. So far it is unclear whether the proliferative capacity of pancreatic islets is restricted by senescence. Materials and Methods: Human pancreatic tissue from n=20 non-diabetic organ donors with a mean age of 50.2 ± 3.5 years (range 7-66 years) and mean BMI of 25.7 ± 0.9 kg/m2 (17.1-33.1 kg/m2) was morphometrically analyzed to determine beta-cell volume, beta-cell replication, beta-cell apoptosis, islet neogenesis and PDX-1 expression. Results: Relative beta-cell volume in human pancreata (mean 2.3 ± 0.2 %) remains constant with aging (r=0.26, p=n.s.). Beta-cell replication (r=0.71, p=0.0004) decreases age-dependently, while beta-cell apoptosis does not change significantly (r=0.42, p=0.08). Concomitantly, PDX-1 expression is downregulated with age in human pancreatic tissue (r=0.65, p=0.002). The rate of islet neogenesis is not affected by aging (r=0.13, p=n.s.). Conclusions: In non-diabetic humans aging is linked with impaired islet turnover possibly due to reduced PDX-1 expression. As beta-cell replication is considered to be the main mechanism responsible for beta-cell regeneration, these changes restrict the flexibility of the aging human pancreas to adapt to changing demands for insulin secretion and increase the risk for the development of diabetes mellitus in older subjects.