Insulin sensitivity in long-living Ames dwarf mice

Area of Science:

• Endocrinology
• Aging Research
• Metabolic Physiology

Background:

• Ames dwarf mice (df/df) exhibit 40-60% lifespan extension and protection from age-related diseases, including insulin resistance.
• Previous studies indicate enhanced insulin signaling in df/df mice, suggesting a link to their longevity.
• The direct impact of enhanced insulin signaling on glucose metabolism in df/df mice remains uncharacterized.

Purpose of the Study:

• To investigate whether enhanced insulin signaling in df/df mice translates to improved insulin action on hepatic glucose production and tissue glucose uptake in vivo.
• To assess tissue-specific insulin sensitivity using hyperinsulinemic-euglycemic clamps in long-living Ames dwarf mice.

Main Methods:

• Hyperinsulinemic-euglycemic clamp studies were conducted in Ames dwarf (df/df) mice and normal (N) littermate controls.
• Assessment of insulin-mediated suppression of hepatic glucose production.
• Quantification of insulin-stimulated glucose uptake in key tissues: gastrocnemius muscle, vastus muscle, and adipose tissue.

Main Results:

• A significantly higher glucose infusion rate (~2-fold) was required to maintain euglycemia in df/df mice compared to N controls.
• Insulin effectively suppressed hepatic glucose production in df/df mice.
• Insulin-stimulated glucose uptake was enhanced in df/df mice in gastrocnemius muscle (100%), vastus muscle (86%), and adipose tissue (65%).

Conclusions:

• Improved insulin signaling in Ames dwarf mice is associated with enhanced tissue-specific insulin action in vivo.
• The improved glucose homeostasis and insulin sensitivity in df/df mice likely contribute to their extended lifespan and healthy aging.
• These findings highlight the critical role of insulin action in the longevity of Ames dwarf mice.