Insulin sensitivity in long-living Ames dwarf mice

    Authors

    D. S. Wiesenborn; J. E. Ayala; E. King;M. M. Masternak

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    Abbreviated Journal Title

    Age

    Keywords

    Ames dwarf; Insulin signaling; Adipose tissue; Clamp; Aging; HYPERINSULINEMIC-EUGLYCEMIC CLAMPS; GENETICALLY HETEROGENEOUS MICE; EXTENDS LIFE-SPAN; GROWTH-HORMONE; LIVED MICE; CALORIC RESTRICTION; GLUCOSE-INTOLERANCE; GENE-EXPRESSION; ADIPOSE-TISSUE; MOUSE; Geriatrics & Gerontology

    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 similar to 2-fold higher in df/df mice compared to N controls. Insulin-mediated glucose production was completely suppressed in dwarfmice, 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.

    Journal Title

    Age

    Volume

    36

    Issue/Number

    5

    Publication Date

    1-1-2014

    Document Type

    Article

    Language

    English

    First Page

    8

    WOS Identifier

    WOS:000343801300011

    ISSN

    0161-9152

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