Aging correlates with decreased beta-cell proliferative capacity and enhanced sensitivity to apoptosis: a potential role for Fas and pancreatic duodenal homeobox-1
Authors: Fabienne Schulthess
Thierry Berney
Desiree M Schumann
José Oberholzer
Domenico Bosco
Kathrin Maedler
Marc Y Donath
Journal: Diabetes (2006)
Discipline: CLINICAL MEDICINE
Keywords: Type 2 diabetes; beta-cell turnover; age; glucose concentration; apoptosis
Affiliations: Larry L. Hillblom Islet Research Center, University of California, Los Angeles, USA.

Abstract:  Type 2 diabetes is characterized by a deficit in beta-cell mass, and its incidence increases with age. Here, we analyzed beta-cell turnover in islets from 2- to 3- compared with 7- to 8-month-old rats and in human islets from 53 organ donors with ages ranging from 17 to 74 years. In cultured islets from 2- to 3-month-old rats, the age at which rats are usually investigated, increasing glucose from 5.5 to 11.1 mmol/l decreased beta-cell apoptosis, which was augmented when glucose was further increased to 33.3 mmol/l. In parallel, beta-cell proliferation was increased by both 11.1 and 33.3 mmol/l glucose compared with 5.5 mmol/l. In contrast, in islets from 7- to 8-month-old rats and from adult humans, increasing glucose concentrations from 5.5 to 33.3 mmol/l induced a linear increase in beta-cell death and a decrease in proliferation. Additionally, in cultivated human islets, age correlated positively with the sensitivity to glucose-induced beta-cell apoptosis and negatively to baseline proliferation. In rat islets, constitutive expression of Fas ligand and glucose-induced Fas receptor expression were observed only in 7- to 8-month-old but not in 2- to 3-month-old islets, whereas no age-dependent changes in the Fas/Fas ligand system could be detected in human islets. However, pancreatic duodenal homeobox (PDX)-1 expression decreased with age in pancreatic tissue sections of rats and humans. Furthermore, older rat islets were more sensitive to the high-glucose-mediated decrease in PDX-1 expression than younger islets. Therefore, differences in glucose sensitivity between human and 2- to 3-month-old rat islets may be due to both differences in age and in the genetic background. These data provide a possible explanation for the increased incidence of type 2 diabetes at an older age and support the use of islets from older rats as a more appropriate model to study glucose-induced beta-cell apoptosis. 

Retracted: No

PubPeer comments:
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 Please copy the left u201ctubulinu201c panel of Fig. 1E, Ardestani et al., J Biol Chem. 2011;286(19):17144-55 (published on March 10, 2011 as Manuscript M110.210526) and paste it into e.g. a photoshop, key note or power point document. The full blot belonging to this slice will appear. Bands 3-6 of the full slice represent the u201etubulinu201c bands given in the paper (follow the green lines) but apparently bands of the full slice show significant similarities to figures shown in earlier papers of the group as well including the present paper. The panel from this paper is indicated by dotted blue lines. ![file] , 
 2018 expression of concern. http: diabetes.diabetesjournals.org content early 2018 09 11 db18-ec2018a.long , 
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 2020 retraction. https: diabetes.diabetesjournals.org content early 2020 01 08 db20-rt03b.full-text.pdf Statement of Retraction. Kathrin Maedler, Desiree M. Schumann, Fabienne Schulthess, Josu00e9 Oberholzer, Domenico Bosco, Thierry Berney, and Marc Y. Donath. Aging Correlates With Decreased b-Cell Proliferative Capacity and Enhanced Sensitivity to Apoptosis: A Potential Role for Fas and Pancreatic Duodenal Homeobox-1. Diabetes 2006;55:2455u20132462. DOI: 10.2337 db05-1586. PMID: 16936193 American Diabetes Association https: doi.org 10.2337 db20-rt03b The above-cited article has been retracted by the American Diabetes Association (ADA), the publisher of Diabetes. This article was previously the subject of an expression of concern in the November 2018 issue of the journal (Diabetes 2018;67:2478u20132479. DOI: 10.2337 db18-ec2018a. PMID: 30213821). In September 2018, ADAu2019s Panel on Ethical Scientific Programs (ESP) contacted the University of Zurich, the lead and corresponding authorsu2019 institution at the time the research was conducted, to request an institutional investigation of concerns related to image manipulation and duplication in the article cited above. The Universityu2019s review is ongoing. The ESP has since coordinated an independent review of the anomalies cited in the expression of concern. On the basis of its review, the ESP has determined that the following instances of potential image duplication compromise the overall reliability of the study. u0001 In the u201cActin, 30 hu201d panel of Fig. 3B, lanes 4 and 6 appear to be duplicates. u0001 In Fig. 4A, lanes 3 and 4 of u201cPDX-1, 96 hu201d panel appear to be duplicates. u0001 In Fig. 4A, lane 2 of the u201cActin, 96 hu201d panel and lane 5 of the u201cPDX-1, 96 hu201d panel appear to be duplicates. u0001 Lanes 3u20136 of the u201cActin, 96hu201d strip of Fig. 3D of this article and lanes 3u20136 of the u201cActin 42 kDAu201d strip in Fig. 3B of Diabetes 55:2713u20132722, with horizontal rotation and contrast and size adjustments, appear to be duplicates. ADA, the publisher of Diabetes, has chosen to retract this publication upon the recommendation of the ESP. Information about ADAu2019s review policies and procedures can be found at diabetesjournals.org content journal-policies. ,