Effects of caloric restriction and growth hormone resistance on insulin-related intermediates in the skeletal muscle.
Growth hormone receptor-deficient (GHRKO) mice are long-lived and have reduced insulin-like growth factor (IGF)-1 and insulin levels and enhanced insulin sensitivity thus resembling the phenotype of animals subjected to calorie restriction (CR). In contrast to its effects in normal mice, CR does not improve insulin sensitivity or increase longevity in GHRKO males. In an attempt to identify mechanisms underlying this differential response to CR, effects of CR on the expression of insulin-related genes were compared in GHRKO and normal mice. In addition to changes detected in both genotypes, and responses unique to GHRKO mice, the levels of Akt2 and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1alpha) were increased and levels of phosphorylated c-Jun N-terminal kinase (JNK)1 were reduced in response to CR only in normal mice. These changes may be related to mechanisms of improving insulin sensitivity and life expectancy.
Al-Regaiey
Khalid A
KA
Departments of Internal Medicine, Southern Illinois University, School of Medicine, Springfield, USA. kalregai@gmail.com
Masternak
Michal M
MM
Bonkowski
Michael S
MS
Panici
Jacob A
JA
Kopchick
John J
JJ
Bartke
Andrzej
A
D055372:AMP-Activated Protein Kinases; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D013006:Growth Hormone / Q000172:deficiency / Q000378:metabolism*; D015151:Immunoblotting; D007333:Insulin Resistance / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000099293:Protein Kinase C-lambda
D055372:AMP-Activated Protein Kinases; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D013006:Growth Hormone; D007527:Isoenzymes; D048055:Mitogen-Activated Protein Kinase 8; D048056:Mitogen-Activated Protein Kinase 9; D009097:Multienzyme Complexes; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000099293:Protein Kinase C-lambda; C474033:FoxO3 protein, mouse; C467200:Foxo1 protein, mouse; C485290:Ppargc1a protein, mouse; C494922:Akt2 protein, mouse