Calorie restriction minimizes activation of insulin signaling in response to glucose: potential involvement of the growth hormone-insulin-like growth factor 1 axis.
Calorie restriction (CR) may modulate insulin signaling in response to energy intake through suppression of the growth hormone (GH)-IGF-1 axis. We investigated the glucose-stimulated serum insulin response and subsequent alterations in insulin receptor (IR), Akt, and FoxO1 in the rat liver and quadriceps femoris muscle (QFM). Nine-month-old wild-type (W) male Wistar rats fed ad libitum (AL) or a 30% CR diet initiated at 6 weeks of age and GH-suppressed transgenic (Tg) rats fed AL were killed 15 min after intraperitoneal injection of glucose or saline. In W-AL rats, the serum insulin concentration was elevated by glucose injection. Concomitantly, the phosphorylated (p)-IR and p-Akt levels were increased in both tissues. The active FoxO1 level was decreased in the liver, but not significantly in the QFM. In W-CR and Tg-AL rats, the serum insulin response was lower, and no significant changes were noted for the p-IR, p-Akt, or active FoxO1 levels in the liver. In the QFM, the p-Akt level was increased in W-CR and Tg-AL rats with an insignificant elevation of p-IR levels. The phenotypic similarity of W-CR and Tg-AL rats suggest that CR minimizes activation of insulin signaling in response to energy intake mostly through the GH-IGF-1 axis.
Hayashi
Hiroko
H
Department of Investigative Pathology, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 12-4 Sakamoto 1-Chome, Nagasaki City, Nagasaki 852-8523, Japan.
Yamaza
Haruyoshi
H
Komatsu
Toshimitsu
T
Park
Seongjoon
S
Chiba
Takuya
T
Higami
Yoshikazu
Y
Nagayasu
Takeshi
T
Shimokawa
Isao
I
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D004268:DNA-Binding Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D013006:Growth Hormone / Q000502:physiology*; D007328:Insulin / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000071161:Forkhead Box Protein O1
D001786:Blood Glucose; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D005947:Glucose; D013006:Growth Hormone; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D009419:Nerve Tissue Proteins; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1