Effects of caloric restriction on insulin pathway gene expression in the skeletal muscle and liver of normal and long-lived GHR-KO mice

Masternak, Michał M.; Al-Regaiey, Khalid; Lim, Marc Michael Del Rosario; Jiménez-Ortega, Vanesa; Panici, Jacob A.; Bonkowski, Michael S.; Bartke, Andrzej

doi:10.1016/j.exger.2005.06.003

Cited by 64 publications

(58 citation statements)

References 20 publications

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“…The levels of IGF1 RNA in the hippocampus of Ames dwarf mice do not differ from the levels measured in normal siblings, although Ames dwarf mice are characterized by suppressed hepatic IGF1 expression and circulating IGF1 levels (41). However, the cardiac expression of IGF1 in young KO mice was decreased in comparison to their normal siblings, which is closer to the findings in the skeletal muscle (7). Interestingly, IGF1R RNA levels were elevated in KO-AL mice in comparison to N-AL and also in young, 3-month-old KO mice, while hGH transgenic mice had reduced level of IGF1R message.…”

Section: Insulin-like Growth Factor-1 and Insulin-like Growth Factor-supporting

confidence: 58%

“…The lack of difference in the cardiac expression of IGF1 RNA between long-lived KO and normal animals was surprising in view of the extremely low levels of circulating IGF1 (nondetectable by Elisa kit) and IGF1 mRNA in the liver of KO animals in comparison to their normal siblings (7). Down regulation of IGF1 biosynthesis in these animals related to the disrupted action of GH clearly does not apply to all organs.…”

Section: Insulin-like Growth Factor-1 and Insulin-like Growth Factor-mentioning

confidence: 99%

“…The mRNA relative expression was analyzed by real-time PCR (RT-PCR) using the "Smart Cycler" instrument (Cepheid, Sunnyvale, CA) with iQ™ SYBR Green Supermix (BIO-RAD) (6,7). The three steps of the RT-PCR included denaturation at 94°C for 2 min, annealing at 62°C for 30 sec with fluorescence reading, and extension at 72°C for 30 sec.…”

Section: Real-time Pcrmentioning

confidence: 99%

“…Results obtained in animals subjected to CR and in various long-lived mutants suggest that perturbations in the insulin signaling pathway may play a key role in extended longevity (5). We have recently described the effects of long-term 30% CR on the expression of genes related to insulin and IGF1 signaling in the liver and skeletal muscle of these animals (6)(7)(8). Effects of insulin on protein metabolism in skeletal muscle and the liver are believed to be important in regulating the substrate availability for the heart (9).…”

Section: Introductionmentioning

confidence: 99%

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Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

Masternak¹,

Al-Regaiey²,

Lim³

et al. 2006

Experimental Gerontology

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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, PPARα and PPARβ/δ in GHR-KO animals. Expression of IR, IRS1, IRS2, IGF1, GLUT4, PPARγ and PPARα 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.

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Section: Insulin-like Growth Factor-1 and Insulin-like Growth Factor-supporting

confidence: 58%

Section: Insulin-like Growth Factor-1 and Insulin-like Growth Factor-mentioning

confidence: 99%

Section: Real-time Pcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

Masternak¹,

Al-Regaiey²,

Lim³

et al. 2006

Experimental Gerontology

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“…One of the most powerful interventions that can extend mammalian longevity is calorie restriction (CR) and at the same time CR alters the expression pattern of genes that are affected by aging (Masternak et al ., 2004, 2005). Beside its known alterations of gene expression, CR can also modulate the pattern of circulating miRNAs in mice (Dhahbi et al ., 2013d).…”

Section: Introductionmentioning

confidence: 99%

Circulating microRNA signature of genotype‐by‐age interactions in the long‐lived Ames dwarf mouse

et al. 2015

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SummaryRecent evidence demonstrates that serum levels of specific miRNAs significantly change with age. The ability of circulating sncRNAs to act as signaling molecules and regulate a broad spectrum of cellular functions implicates them as key players in the aging process. To discover circulating sncRNAs that impact aging in the long‐lived Ames dwarf mice, we conducted deep sequencing of small RNAs extracted from serum of young and old mice. Our analysis showed genotype‐specific changes in the circulating levels of 21 miRNAs during aging [genotype‐by‐age interaction (GbA)]. Genotype‐by‐age miRNAs showed four distinct expression patterns and significant overtargeting of transcripts involved in age‐related processes. Functional enrichment analysis of putative and validated miRNA targets highlighted cellular processes such as tumor suppression, anti‐inflammatory response, and modulation of Wnt, insulin, mTOR, and MAPK signaling pathways, among others. The comparative analysis of circulating GbA miRNAs in Ames mice with circulating miRNAs modulated by calorie restriction (CR) in another long‐lived mouse suggests CR‐like and CR‐independent mechanisms contributing to longevity in the Ames mouse. In conclusion, we showed for the first time a signature of circulating miRNAs modulated by age in the long‐lived Ames mouse.

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The Janus Face of Insulin in Brain

Duarte

Candeias

Correia

et al. 2013

Metabolic Syndrome and Neurological Disorders

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Effects of caloric restriction on insulin pathway gene expression in the skeletal muscle and liver of normal and long-lived GHR-KO mice

Cited by 64 publications

References 20 publications

Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

Circulating microRNA signature of genotype‐by‐age interactions in the long‐lived Ames dwarf mouse

The Janus Face of Insulin in Brain

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