title: Calorie restriction initiated at middle age improved glucose tolerance without affecting age-related impairments of insulin signaling in rat skeletal muscle.
abstract: Calorie restriction (CR) may affect glucose tolerance via modulation of the insulin action in skeletal muscle. The present study investigated the effect of CR initiated at middle age in rats bearing glucose intolerance, in comparison with CR at a younger age. Male F344 rats at 2.5 and 18months (mo) of age were fed ad libitum (AL) or 30% CR diets for 4-4.5mo, subjected to glucose tolerance testing, and then sacrificed 15min after intraperitoneal glucose or saline injection to evaluate glucose-stimulated insulin response and subsequent activation of insulin signaling molecules. The protein abundance of phosphorylated (p) insulin receptors, p-Akt, and p-atypical PKC and the membrane fraction of glucose transporter 4 in quadriceps femoris muscle (QFM) were analyzed by EIA or immunoblotting. CR initiated either at young or middle age improved glucose tolerance with a lower serum insulin response to glucose. However, middle-aged CR did not improve aging-related impairments in insulin signaling in QFM. The present results emphasized the possibilities of CR activation of an insulin-independent mechanism in skeletal muscle and also of the involvement of non-muscle tissues in glucose uptake.
authors.affiliation: Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki City 852-8523, Japan.
authors.forename: Seongjoon
authors.initials: S
authors.lastname: Park
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Komatsu
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hayashi
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Yamaza
authors.forename: Takuya
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Higami
authors.forename: Kazunao
authors.initials: K
authors.lastname: Kuramoto
authors.forename: Isao
authors.initials: I
authors.lastname: Shimokawa
mesh_terms: D000273:Adipose Tissue / Q000502:physiology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D031204:Caloric Restriction / Q000379:methods*; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000032:analysis; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D008565:Membrane Proteins; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose