title: Insulin sensitivity in long-living Ames dwarf mice.
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.
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 6900 Lake Nona Blvd., Orlando, FL, 32827, USA.
authors.forename: Denise S
authors.initials: DS
authors.lastname: Wiesenborn
authors.forename: Julio E
authors.initials: JE
authors.lastname: Ayala
authors.forename: Emily
authors.initials: E
authors.lastname: King
authors.forename: Michal M
authors.initials: MM
authors.lastname: Masternak
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004195:Disease Models, Animal; D004393:Dwarfism, Pituitary / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008136:Longevity / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D007328:Insulin