Objective: Aging is believed to induce insulin resistance in humans. However, when and how insulin sensitivity changes with aging remain unclear in both humans and mice.

Methods: Groups of C57BL/6N mice at 9-15 weeks (young), 34-67 weeks (one-year-old) and 107-121 weeks (two-year-old) of age underwent hyperinsulinemic-euglycemic clamp studies with somatostatin infusion under awake and non-restrained conditions.

Results: The glucose infusion rates for maintaining euglycemia were 17.11±2.94, 5.58±1.28 and 25.30±4.42 mg/kg/min in young, one-year-old and two-year-old mice, respectively. Thus, compared with young mice, one-year-old mice exhibited the expected insulin resistance. In contrast, the insulin sensitivity of two-year-old mice showed significant improvement. These age-related changes were mainly observed in glucose uptake into adipose tissue and skeletal muscle. Epididymal fat weight and hepatic triglyceride levels were highest in one-year-old mice, while being similar in young and two-year-old mice.

Conclusions: Our observations indicate that, in mice, insulin resistance appears at one year of age but subsequently improves markedly. These alterations in insulin sensitivity are attributable to changes in visceral fat accumulations and age-related factors.


H.Kondo: None. H.Ono: None. K.Yokote: None.


Japan Society for the Promotion of Science (15K09398, 18K08502, 20H00524); Japan Agency for Medical Research and Development (17GM5010002H0001, 18GM5010002H0002, 19GM5010002H0003, 20GM5010002H0004)

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