Shortened {beta}-cell lifespan leads to {beta}-cell deficit in a rodent model of type 2 diabetes

Am J Physiol Endocrinol Metab. 2011 May;300(5):E933-8. doi: 10.1152/ajpendo.00504.2010. Epub 2011 Feb 22.

Abstract

Since the fundamental defect in both type 1 and type 2 diabetes is β-cell failure, there is increasing interest in the capacity, if any, for β-cell regeneration. Insights into typical β-cell age and lifespan during normal development and how these are influenced in diabetes is desirable to realistically establish the prospects for β-cell regeneration as means to reverse the deficit in β-cell mass in diabetes. We assessed the mean β-cell age and lifespan by the classical McKendrick-von Foester equation that describes the age-based heterogeneity of β-cells in terms of the time-varying β-cell formation and loss estimated by a β-cell turnover model. This modeling approach was applied to evaluate β-cell lifespan in a rodent model of type 2 diabetes in comparison with nondiabetic controls. When rats were 10 mo old, mean β-cell lifespan was 1 mo vs. 6 mo in rats with type 2 diabetes vs. controls. A shortened β-cell lifespan in a rat model of type 2 diabetes results in a decrease in mean β-cell age and thus contributes to decreased β-cell mass.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology
  • Algorithms
  • Animals
  • Animals, Genetically Modified
  • Apoptosis / physiology
  • Cell Count
  • Cell Death / physiology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology*
  • Humans
  • In Situ Nick-End Labeling
  • Insulin-Secreting Cells / pathology*
  • Longevity / physiology*
  • Models, Statistical
  • Rats
  • Rats, Sprague-Dawley