Genetic inactivation of GIP signaling reverses aging-associated insulin resistance through body composition changes.
Aging is associated with increased fat mass and decreased lean mass, which is strongly associated with the development of insulin resistance. Gastric inhibitory polypeptide (GIP) is known to promote efficient storage of ingested nutrients into adipose tissue; we examined aging-associated changes in body composition using 10-week-old and 50-week-old wild-type (WT) and GIP receptor knockout (Gipr-/-) mice on a normal diet, which show no difference in body weight. We found that Gipr-/- mice showed significantly reduced fat mass without reduction of lean mass or food intake, while WT mice showed increased fat mass and decreased lean mass associated with aging. Moreover, aged Gipr-/- mice showed improved insulin sensitivity, which is associated with amelioration in glucose tolerance, higher plasma adiponectin levels, and increased spontaneous physical activity. We therefore conclude that genetic inactivation of GIP signaling can prevent the development of aging-associated insulin resistance through body composition changes.
Yamada
Chizumi
C
Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Yamada
Yuichiro
Y
Tsukiyama
Katsushi
K
Yamada
Kotaro
K
Yamane
Shunsuke
S
Harada
Norio
N
Miyawaki
Kazumasa
K
Seino
Yutaka
Y
Inagaki
Nobuya
N
D054392:Adipokines / Q000097:blood; D000273:Adipose Tissue / Q000033:anatomy & histology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology*; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics* / Q000502:physiology*; D005951:Glucose Tolerance Test; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D015398:Signal Transduction / Q000502:physiology*
D054392:Adipokines; D001786:Blood Glucose; D005749:Gastric Inhibitory Polypeptide