Metabolic consequences of pregnancy-associated plasma protein-A deficiency in mice: Exploring possible relationship to the longevity phenotype

Cheryl A. Conover, Megan A. Mason, James A. Levine, Colleen M. Novak

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Mice born with the deletion of the gene for pregnancy-associated plasma protein-A (PAPP-A), a model of reduced local IGF activity, live ∼30% longer than their wild-type (WT) littermates. In this study, we investigated metabolic consequences of PAPP-A gene deletion and possible relationship to lifespan extension. Specifically, we determined whether 18-month-old PAPP-A knockout (KO) mice when compared with their WT littermates have reduced energy expenditure and/or altered glucose-insulin sensitivity. Food intake, and total energy expenditure and resting energy expenditure as measured by calorimetry were not different between PAPP-A KO and WT mice when subjected to the analysis of covariance with body weight as the covariate. However, there was an increase in spontaneous physical activity in PAPP-A KO mice. Both WT and PAPP-A KO mice exhibited mild insulin resistance with age, as assessed by fasting glucose/insulin ratios. Oral glucose tolerance and insulin sensitivity were not significantly different between the two groups of mice, although there appeared to be a decrease in the average size of the pancreatic islets in PAPP-A KO mice. Thus, neither reduced 'rate of living' nor altered glucose-insulin homeostasis can be considered key determinants of the enhanced longevity of PAPP-A KO mice. These findings are discussed in the context of those from other long-lived mouse models.

Original languageEnglish (US)
Pages (from-to)599-605
Number of pages7
JournalJournal of Endocrinology
Volume198
Issue number3
DOIs
StatePublished - Sep 1 2008

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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