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Insulin sensitivity in long-living Ames dwarf mice

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Abstract

Long-living Ames dwarf mice (df/df) characterized by growth hormone (GH) deficiency are widely used in aging research because of their 40–60 % lifespan extension compared to normal (N) littermates. Importantly, these mice not only live longer but are also protected from age-related diseases including insulin resistance. Several studies demonstrate that df/df mice have enhanced insulin signaling in different insulin-sensitive tissues and suggest that this is a mechanism for extended lifespan. However, it is unknown whether the enhanced insulin signaling in df/df mice translates to improved insulin action on hepatic glucose production and tissue glucose uptake. We performed hyperinsulinemic-euglycemic clamps to assess tissue-specific insulin action in vivo for the first time in these small long-living dwarfs. Our results demonstrate that the glucose infusion rate required to maintain euglycemia was ∼2-fold higher in df/df mice compared to N controls. Insulin-mediated glucose production was completely suppressed in dwarf mice, and stimulation of gastrocnemius and vastus muscle and adipose tissue glucose uptake was also enhanced in df/df mice (100, 86, and 65 %, respectively). These findings show that improved insulin signaling in df/df mice is associated with enhanced tissue-specific insulin action in vivo. This improved functionality of insulin action and glucose homeostasis may play a key role in promoting healthy aging and longer lifespan in df/df mice.

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Acknowledgments

Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award number R01AG032290 and P01AG031736.

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Authors and Affiliations

  1. Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 6900 Lake Nona Blvd., Orlando, FL, 32827, USA

    Denise S. Wiesenborn & Michal M. Masternak

  2. Sanford-Burnham Medical Research Institute at Lake Nona, Orlando, FL, 32827, USA

    Julio E. Ayala & Emily King

Authors
  1. Denise S. Wiesenborn
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  2. Julio E. Ayala
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  3. Emily King
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  4. Michal M. Masternak
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Correspondence to Michal M. Masternak.

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Wiesenborn, D.S., Ayala, J.E., King, E. et al. Insulin sensitivity in long-living Ames dwarf mice. AGE 36, 9709 (2014). https://doi.org/10.1007/s11357-014-9709-1

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  • DOI: https://doi.org/10.1007/s11357-014-9709-1

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