Insulin sensitivity in long-living Ames dwarf mice
Abbreviated Journal Title
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
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.
"Insulin sensitivity in long-living Ames dwarf mice" (2014). Faculty Bibliography 2010s. 6281.