title: Genetic inactivation of GIP signaling reverses aging-associated insulin resistance through body composition changes.
abstract: 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.
authors.affiliation: Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Chizumi
authors.initials: C
authors.lastname: Yamada
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tsukiyama
authors.forename: Kotaro
authors.initials: K
authors.lastname: Yamada
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamane
authors.forename: Norio
authors.initials: N
authors.lastname: Harada
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Miyawaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
mesh_terms: 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*
chemical_list: D054392:Adipokines; D001786:Blood Glucose; D005749:Gastric Inhibitory Polypeptide