Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases
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Aging / genetics
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Aging / metabolism*
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Animals
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Caloric Restriction*
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Enzyme-Linked Immunosorbent Assay
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Female
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Forkhead Box Protein O1
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Forkhead Box Protein O3
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism
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Gene Expression Regulation, Developmental
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Growth Hormone / deficiency
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Growth Hormone / metabolism*
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Immunoblotting
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Insulin Resistance / physiology*
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Male
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinase 8 / genetics
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Mitogen-Activated Protein Kinase 8 / metabolism
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Mitogen-Activated Protein Kinase 9 / genetics
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Mitogen-Activated Protein Kinase 9 / metabolism
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Multienzyme Complexes / genetics
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Multienzyme Complexes / metabolism
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Muscle, Skeletal / cytology
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Muscle, Skeletal / metabolism*
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Phosphorylation
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Protein Kinase C / genetics
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Protein Kinase C / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors
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Zebrafish Proteins
Substances
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Forkhead Box Protein O1
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Forkhead Box Protein O3
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Forkhead Transcription Factors
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FoxO3 protein, mouse
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Foxo1 protein, mouse
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Isoenzymes
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Multienzyme Complexes
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Ppargc1a protein, mouse
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RNA, Messenger
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Trans-Activators
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Transcription Factors
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Zebrafish Proteins
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Growth Hormone
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Mitogen-Activated Protein Kinase 9
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Akt2 protein, mouse
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Protein Kinase C
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protein kinase C lambda
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Mitogen-Activated Protein Kinase 8
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AMP-Activated Protein Kinases