Effects of caloric restriction on insulin pathway gene expression in the skeletal muscle and liver of normal and long-lived GHR-KO mice.
Growth hormone receptor/binding protein knockout (GHR-KO) mice are characterized by resistance to growth hormone (GH), reduced insulin like growth factor 1 (IGF1) levels and enhanced insulin sensitivity and markedly increased lifespan. Findings in these and other long-lived mutant mice, and in normal animals subjected to caloric restriction (CR) indicate that insulin signaling is importantly involved in the control of longevity. We have examined the mRNA expression level of genes involved in insulin/IGF1 action in the skeletal muscle and liver of normal and GHR-KO mice fed ad libitum or subjected to long term 30% CR. The levels of IR, IRS1, IRS2, GLUT4 and IGF1 message in the skeletal muscle were reduced by CR in both normal and GHR-KO mice. In the liver, the results indicate that in GHR-KO mice mRNA expression of genes related to early steps of insulin signaling is up-regulated in the liver but not in the muscle. The results also show that improved insulin sensitivity in response to CR is not due to increased mRNA expression of the above genes in either normal or GHR-KO animals.
Masternak
Michal M
MM
Departments of Internal Medicine and Physiology, Geriatrics Research, Southern Illinois University, School of Medicine, P.O. Box 19628, Springfield, IL 62794-9628, 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
Bartke
Andrzej
A
D000818:Animals; D031204:Caloric Restriction; D005838:Genotype; D051275:Glucose Transporter Type 4 / Q000235:genetics; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000235:genetics; D011972:Receptor, Insulin / Q000235:genetics; D011986:Receptors, Somatotropin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526295:Irs1 protein, mouse; C526298:Irs2 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin