Effects of Long-Term Caloric Restriction on Early Steps of the Insulin-Signaling System in Mouse Skeletal Muscle

Argentino, Danila P.; Dominici, Fernando Pablo; Al-Regaiey, Khalid; Bonkowski, Michael S.; Bartke, Andrzej; Turyn, Daniel

doi:10.1093/gerona/60.1.28

Cited by 35 publications

(34 citation statements)

References 19 publications

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“…GLUT4 abundance was not significantly altered in the muscles after prolonged incubation with reduced glucose and insulin. These results are consistent with most earlier research on in vivo CR, which indicates no effect of CR on skeletal muscle GLUT4 total abundance (2,4,12,22,39), although one previous study reported an increase in mouse muscle GLUT4 with CR (3). GLUT1 abundance was unaffected in the present study, consistent with the lack of an effect of in vivo CR on GLUT1 from rat soleus or white gastrocnemius muscles, although a CR-associated increase in GLUT1 was found in a mixed sample of whole gastrocnemius and quadriceps muscles (40).…”

Section: Discussionsupporting

confidence: 92%

“…Previous research that quantified insulin receptors in skeletal muscle using various methods, including Western blotting (2)(3)(4)42) and insulin receptor binding (7,14), has usually found no effect of CR, consistent with the present results, although Wang et al (39) reported increased insulin receptor binding in rat skeletal muscle after CR. Two studies have indicated that insulin receptor tyrosine phosphorylation can be increased by CR in muscle (3,18), whereas an equal number of studies have not found this effect of CR (2,4).…”

Section: Discussionsupporting

confidence: 91%

“…Two studies have indicated that insulin receptor tyrosine phosphorylation can be increased by CR in muscle (3,18), whereas an equal number of studies have not found this effect of CR (2,4). In addition, Zhu et al (42,43) found that CR led to increased insulin receptor tyrosine phosphorylation in muscle from old, but not young, rats.…”

Section: Discussionmentioning

confidence: 99%

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In vitro simulation of calorie restriction-induced decline in glucose and insulin leads to increased insulin-stimulated glucose transport in rat skeletal muscle

Arias¹,

Cartee²

2007

American Journal of Physiology-Endocrinology and Metabolism

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Arias EB, Cartee GD. In vitro simulation of calorie restrictioninduced decline in glucose and insulin leads to increased insulinstimulated glucose transport in rat skeletal muscle. Am J Physiol Endocrinol Metab 293: E1782-E1788, 2007. First published October 9, 2007; doi:10.1152/ajpendo.00531.2007.-In vivo calorie restriction [CR; consuming 60% of ad libitum (AL) intake] induces elevated insulin-stimulated glucose transport (GT) in skeletal muscle. The mechanisms triggering this adaptation are unknown. The aim of this study was to determine whether physiological reductions in extracellular glucose and/or insulin, similar to those found with in vivo CR, were sufficient to elevate GT in isolated muscles. Epitrochlearis muscles dissected from rats were incubated for 24 h in media with glucose (8 mM) and insulin (80 U/ml) at levels similar to plasma values of AL-fed rats and compared with muscles incubated with glucose (5.5 mM) and/or insulin (20 U/ml) at levels similar to plasma values of CR rats. Muscles incubated with CR levels of glucose and insulin for 24 h had a subsequently greater (P Ͻ 0.005) GT with 80 U/ml insulin and 8 mM [3 H]-3-O-methylglucose but unchanged GT without insulin. Reducing only glucose or insulin for 24 h or both glucose and insulin for 6 h did not induce altered GT. Increased GT after 24-h incubation with CR levels of glucose and insulin was not attributable to increased insulin receptor tyrosine phosphorylation, Akt serine phosphorylation, or Akt substrate of 160 kDa phosphorylation. Nor did 24-h incubation with CR levels of glucose and insulin alter the abundance of insulin receptor, insulin receptor substrate-1, GLUT1, or GLUT4 proteins. These results provide the proof of principle that reductions in extracellular glucose and insulin, similar to in vivo CR, are sufficient to induce an increase in insulin-stimulated glucose transport comparable to the increase found with in vivo CR. diet restriction; insulin signaling; GLUT4; Akt; Akt substrate of 160 kDa ALTERED SKELETAL MUSCLE GLUCOSE transport can contribute to important systemic changes in glucose homeostasis. For example, skeletal muscle insulin resistance for glucose uptake is an early and essential defect for the subsequent development of the metabolic syndrome and type 2 diabetes mellitus (19,20). Previous studies have demonstrated that prior exposure of skeletal muscle to large changes in extracellular glucose and insulin concentrations over a period of hours can lead to altered glucose transport. However, only a few studies have characterized the effects of moderate physiological changes in glucose on glucose transport. In cultured myocytes, increasing glucose from ϳ5 to ϳ8 -10 mM for 24 h did not markedly reduce glucose transport (31, 38). In isolated rat soleus muscles, there was also little difference in glucose uptake without insulin after 3 h of incubation with ϳ5 compared with ϳ8 mM glucose (38), but it is possible that a more prolonged incubation would reveal an effect in this range of glucose concentrations.Knowledge i...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

In vitro simulation of calorie restriction-induced decline in glucose and insulin leads to increased insulin-stimulated glucose transport in rat skeletal muscle

Arias¹,

Cartee²

2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Indeed, studies using the PI3K inhibitor, wortmannin (6), and mice with KO of Akt2 (3), reveal that PI3K and Akt2 are essential for the ability of brief CR to enhance skeletal muscle insulin sensitivity. In contrast, CR does not appear to augment insulin action upstream of PI3K at the level of the IR or Irs1 in response to submaximal insulin (9) but has been shown to enhance IR-Irs1 activation in response to supraphysiological insulin stimulation (8,9,11,23), although this is not a universal finding (24,25). In addition, mice with KO of Irs1 exhibit the expected increase in skeletal muscle insulin sensitivity after CR (26).…”

Section: Discussionmentioning

confidence: 99%

Sirt1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction

Schenk¹,

McCurdy²,

Philp³

et al. 2011

J. Clin. Invest.

169

186

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Skeletal muscle insulin resistance is a key component of the etiology of type 2 diabetes. Caloric restriction (CR) enhances the sensitivity of skeletal muscle to insulin. However, the molecular signals within skeletal muscle linking CR to improved insulin action remain largely unknown. Recently, the mammalian ortholog of Sir2, sirtuin 1 (Sirt1), has been identified as a potential transducer of perturbations in cellular energy flux into subsequent metabolic adaptations, including modulation of skeletal muscle insulin action. Here, we have demonstrated that CR increases Sirt1 deacetylase activity in skeletal muscle in mice, in parallel with enhanced insulin-stimulated phosphoinositide 3-kinase (PI3K) signaling and glucose uptake. These adaptations in skeletal muscle insulin action were completely abrogated in mice lacking Sirt1 deacetylase activity. Mechanistically, Sirt1 was found to be required for the deacetylation and inactivation of the transcription factor Stat3 during CR, which resulted in decreased gene and protein expression of the p55α/p50α subunits of PI3K, thereby promoting more efficient PI3K signaling during insulin stimulation. Thus, these data demonstrate that Sirt1 is an integral signaling node in skeletal muscle linking CR to improved insulin action, primarily via modulation of PI3K signaling.

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“…IR function of skeletal muscle after CR has been reported to be unaltered in some (3,4,6,7,15,52), but not all (4,19,48,53), studies. Enhanced insulin-stimulated glucose transport in rat skeletal muscle in response to CR has been found in the absence of significantly elevated IRS1-PI3K activity (17)(18)(19).…”

mentioning

confidence: 99%

Mechanisms for increased insulin-stimulated Akt phosphorylation and glucose uptake in fast- and slow-twitch skeletal muscles of calorie-restricted rats

Sharma¹,

Arias²,

Bhat³

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Sajan MP, Farese RV, Cartee GD. Mechanisms for increased insulin-stimulated Akt phosphorylation and glucose uptake in fastand slow-twitch skeletal muscles of calorie-restricted rats. Am J Physiol Endocrinol Metab 300: E966 -E978, 2011. First published March 8, 2011 doi:10.1152/ajpendo.00659.2010.-Calorie restriction [CR; ϳ65% of ad libitum (AL) intake] improves insulin-stimulated glucose uptake (GU) and Akt phosphorylation in skeletal muscle. We aimed to elucidate the effects of CR on 1) processes that regulate Akt phosphorylation [insulin receptor (IR) tyrosine phosphorylation, IR substrate 1-phosphatidylinositol 3-kinase (IRS-PI3K) activity, and Akt binding to regulatory proteins (heat shock protein 90, Appl1, protein phosphatase 2A)]; 2) Akt substrate of 160-kDa (AS160) phosphorylation on key phosphorylation sites; and 3) atypical PKC (aPKC) activity. Isolated epitrochlearis (fast-twitch) and soleus (slow-twitch) muscles from AL or CR (6 mo duration) 9-moold male F344BN rats were incubated with 0, 1.2, or 30 nM insulin and 2-deoxy-[ 3 H]glucose. Some CR effects were independent of insulin dose or muscle type: CR caused activation of Akt (Thr 308 and Ser 473 ) and GU in both muscles at both insulin doses without CR effects on IRS1-PI3K, Akt-PP2A, or Akt-Appl1. Several muscle-and insulin dose-specific CR effects were revealed. Akt-HSP90 binding was increased in the epitrochlearis; AS160 phosphorylation (Ser 588 and Thr 642 ) was greater for CR epitrochlearis at 1.2 nM insulin; and IR phosphorylation and aPKC activity were greater for CR in both muscles with 30 nM insulin. On the basis of these data, our working hypothesis for improved insulin-stimulated GU with CR is as follows:

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Effects of Long-Term Caloric Restriction on Early Steps of the Insulin-Signaling System in Mouse Skeletal Muscle

Cited by 35 publications

References 19 publications

In vitro simulation of calorie restriction-induced decline in glucose and insulin leads to increased insulin-stimulated glucose transport in rat skeletal muscle

In vitro simulation of calorie restriction-induced decline in glucose and insulin leads to increased insulin-stimulated glucose transport in rat skeletal muscle

Sirt1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction

Mechanisms for increased insulin-stimulated Akt phosphorylation and glucose uptake in fast- and slow-twitch skeletal muscles of calorie-restricted rats

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