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. 2014;36(5):9709.
doi: 10.1007/s11357-014-9709-1. Epub 2014 Aug 29.

Insulin sensitivity in long-living Ames dwarf mice

Denise S Wiesenborn  1 , Julio E Ayala, Emily King, Michal M Masternak
Affiliations

Insulin sensitivity in long-living Ames dwarf mice

Denise S Wiesenborn et al. Age (Dordr). 2014.

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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Figures

Fig. 1
Fig. 1
Insulin and glucose level of normal and df/df mice before and during clamp. n = 8 animals per genotype. *P < 0.05
Fig. 2
Fig. 2
Arterial glucose (a) and glucose infusion rate (b) during insulin clamp in normal (N) and Ames dwarf (df/df) mice. n = 8 mice per genotype. *P < 0.05
Fig. 3
Fig. 3
EndoRa during basal conditions (black bars) and during insulin clamps (white bars) in normal (N) and Ames dwarf (df/df) mice
Fig. 4
Fig. 4
Glucose metabolic index (Rg) in soleus (a), gastrocnemius (b), superficial vastus lateralis (c), fat (d), heart (e), and brain (e) during insulin clamps in normal (N) and Ames dwarf (df/df) mice. n = 8 mice per genotype. *P < 0.05
See this image and copyright information in PMC

References

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