Title

Insulin Sensitivity In Long-Living Ames Dwarf Mice

Keywords

Adipose tissue; Aging; Ames dwarf; Clamp; Insulin signaling

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.

Publication Date

10-1-2014

Publication Title

Age

Volume

36

Issue

5

Number of Pages

-

Document Type

Article

Personal Identifier

scopus

DOI Link

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

Socpus ID

84906451949 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84906451949

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