Caloric restriction and growth hormone receptor knockout: effects on expression of genes involved in insulin action in the heart.
Blockade of growth hormone (GH), decreased insulin-like growth factor-1 (IGF1) action and increased insulin sensitivity are associated with life extension and an apparent slowing of the aging process. We examined expression of genes involved in insulin action, IR, IRS1, IRS2, IGF1, IGF1R, GLUT4, PPARs and RXRs in the hearts of normal and GHR-/- (KO) mice fed ad libitum or subjected to 30% caloric restriction (CR). CR increased the cardiac expression of IR, IRS1, IGF1, IGF1R and GLUT4 in normal mice and IRS1, GLUT4, PPARalpha and PPARbeta/delta in GHR-KO animals. Expression of IR, IRS1, IRS2, IGF1, GLUT4, PPARgamma and PPARalpha did not differ between GHR-KO and normal mice. These unexpected results suggest that CR may lead to major modifications of insulin action in the heart, but high insulin sensitivity of GHR-KO mice is not associated with alterations in the levels of most of the examined molecules related to intracellular insulin signaling.
Masternak
Michal M
MM
Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA. mmasternak@siumed.edu
Al-Regaiey
Khalid A
KA
Del Rosario Lim
Marc Michael
MM
Jimenez-Ortega
Vanesa
V
Panici
Jacob A
JA
Bonkowski
Michael S
MS
Kopchick
John J
JJ
Wang
Zhihui
Z
Bartke
Andrzej
A
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D031204:Caloric Restriction; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism*; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology*
D002352:Carrier Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D048068:PPAR-beta; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D047488:Retinoid X Receptors; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; C051815:somatotropin-binding protein