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Impaired islet turnover with aging

13 Feb 2009


The prevalence of type 2 diabetes mellitus increases with age, and it is currently unclear whether the capacity of ß cell mass to compensate for changing insulin demands is restricted with aging. In type 2 diabetes, which occurs more frequently in older subjects, increased ß cell apoptosis leads to ß cell deficiency. Pancreatic duodenal homeobox-1 (PDX-1) is known to be a direct activator of several ß cell specific genes including those that control glucose metabolism, and is a promoter of ß cell replication. This study by Reers et al aimed to examine the association between islet and ß cell turnover with aging and the role of PDX-1. Human pancreatic donor tissue from 20 non-diabetic donors was morphometrically analyzed to measure ß cell volume, ß cell replication, ß cell apoptosis, islet neogenesis and PDX-1 expression. Relative ß cell volume and apoptosis were found to remain constant with aging, while ß cell replication decreased with age. PDX-1 expression was lower with age, suggesting a possible link with impaired islet turnover. The authors suggest that these changes in ß cell replication with age reduce the ability of the human pancreas to respond to changes in insulin demands, increasing the risk of developing type 2 diabetes mellitus. Reers, C., Erbel, S., Esposito, I., Schmied, B., Büchler, M.W., Nawroth, P.P., Ritzel, R.A. European Journal of Endocrinology 160: 185-191 DOI: 10.1530/EJE-08-0596