title: Shortened {beta}-cell lifespan leads to {beta}-cell deficit in a rodent model of type 2 diabetes.
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.
authors.affiliation: Dept. of Information Engineering, Univ. of Padova, Via Gradenigo 6 B, 35129 Padova, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Manesso
authors.forename: Gianna M
authors.initials: GM
authors.lastname: Toffolo
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Butler
authors.forename: Peter C
authors.initials: PC
authors.lastname: Butler
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
mesh_terms: D000375:Aging / Q000502:physiology; D000465:Algorithms; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008136:Longevity / Q000502:physiology*; D015233:Models, Statistical; D051381:Rats; D017207:Rats, Sprague-Dawley