Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia

Wilkes, Emilie; Selby, Anna; Atherton, Philip J.; Patel, Rekha; Rankin, Debbie; Smith, Kyle; Rennie, Michael J.

doi:10.3945/ajcn.2009.27543

Cited by 178 publications

(155 citation statements)

References 34 publications

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“…These findings are consistent with other studies that have reported a reduction in response to insulin [30,32,37,39,42,44] with the exception of three studies, which did not observe any significant change in MPB [45,47,48]. This might well be due to anabolic resistance to insulin in a relatively older study population and the presence of diabetes mellitus.…”

Section: Discussionsupporting

confidence: 82%

Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis

et al. 2015

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Aims/hypothesis We aimed to investigate the role of insulin in regulating human skeletal muscle metabolism in health and diabetes. Methods We conducted a systematic review and metaanalysis of published data that examined changes in skeletal muscle protein synthesis (MPS) and/or muscle protein breakdown (MPB) in response to insulin infusion. Random-effects models were used to calculate weighted mean differences (WMDs), 95% CIs and corresponding p values. Both MPS and MPB are reported in units of nmol (100 ml leg vol.)Results A total of 104 articles were examined in detail. Of these, 44 and 25 studies (including a total of 173 individuals) were included in the systematic review and meta-analysis, respectively. In the overall estimate, insulin did not affect MPS 8.55], p=0.71), but significantly reduced MPB .18], p<0.001). Overall, insulin significantly increased net balance protein acquisition (WMD 20.09 [95% CI 15.93,24.26], p<0.001). Subgroup analysis of the effect of insulin on MPS according to amino acid (AA) delivery was performed using meta-regression analysis. The estimate size (WMD) was significantly different between subgroups based on AA availability (p=0.001). An increase in MPS was observed when AA availability increased (WMD 13.44 [95% CI 4.07,22.81], p<0.01), but not when AA availability was reduced or unchanged. In individuals with diabetes and in the presence of maintained delivery of AA, there was a significant reduction in MPS in response to insulin (WMD −6.67 [95% CI −12.29, −0.66], p<0.05). Conclusions/interpretation This study demonstrates the complex role of insulin in regulating skeletal muscle metabolism. Insulin appears to have a permissive role in MPS in the presence of elevated AAs, and plays a clear role in reducing MPB independent of AA availability.

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Section: Discussionsupporting

confidence: 82%

Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis

et al. 2015

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“…In the early post-prandial period, plasma amino acid levels and [1-13 C]phenylalanine enrichments tended to be higher in the young versus the older group. This apparent delay in plasma amino acid concentrations and enrichments can be accounted for by either a delayed digestion and/or absorption rate (Boirie et al 1997;Volpi et al 1999;Koopman et al 2009b;Pennings et al 2011b), and/or a greater amino acid uptake secondary to the compensatory hyperinsulinemia (Hatzakorzian et al 2011) (Fig.1b), and/or an attenuated inhibition of the post-prandial reduction in protein breakdown (Wilkes et al 2009). …”

Section: Discussionmentioning

confidence: 99%

The muscle protein synthetic response to the combined ingestion of protein and carbohydrate is not impaired in healthy older men

Kiskini

Hamer

Wall

et al. 2013

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Aging is associated with a progressive decline in skeletal muscle mass. It has been hypothesized that an attenuated muscle protein synthetic response to the main anabolic stimuli may contribute to the age-related loss of muscle tissue. The aim of the present study was to compare the muscle protein synthetic response following ingestion of a meal-like amount of dietary protein plus carbohydrate between healthy young and older men.

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“…Several groups have identified anabolic resistance in human muscle (21)(22)(23)(24)(25) and Rennie's group have reported a blunting of both the stimulation of protein synthesis by amino acids (23) and the inhibition of proteolysis by insulin (25) in the healthy elderly compared with younger adults. This is linked to anabolic signalling deficits which mean that the nutrient signal provided by essential amino acids is not sensed or transduced as well by old muscle as it is by young muscle, resulting in a lower response of protein synthesis to the same nutrient stimulus.…”

Section: Anabolic Resistance: Dietary Protein Intakesmentioning

confidence: 99%

Nutrition and sarcopenia: evidence for an interaction

Millward

2012

Proc. Nutr. Soc.

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Nutritional interventions that might influence sarcopenia, as indicated by literature reporting on sarcopenia per se as well as dynapenia and frailty, are reviewed in relation to potential physiological aetiological factors, i.e. inactivity, anabolic resistance, inflammation, acidosis and vitamin D deficiency. As sarcopenia occurs in physically active and presumably well-nourished populations, it is argued that a simple nutritional aetiology is unlikely and unequivocal evidence for any nutritional influence is extremely limited. Dietary protein is probably the most widely researched nutrient but only for frailty is there one study showing evidence of an aetiological influence and most intervention studies with protein or amino acids have proved ineffective with only a very few exceptions. Fish oil has been shown to attenuate anabolic resistance of muscle protein synthesis in one study. There is limited evidence for a protective influence of antioxidants and inducers of phase 2 proteins on sarcopenia, dynapenia and anabolic resistance in human and animal studies. Also fruit and vegetables may protect against acidosis-induced sarcopenia through their provision of dietary potassium. While severe vitamin D deficiency is associated with dynapenia and sarcopenia, the evidence for a beneficial influence of increasing vitamin D status above the severe deficiency level is limited and controversial, especially in men. On this basis there is insufficient evidence for any more specific nutritional advice than that contained in the general healthy lifestyle-healthy diet message: i.e. avoiding inactivity and low intakes of food energy and nutrients and maintain an active lifestyle with a diet providing a rich supply of fruit and vegetables and frequent oily fish. Aging: Dynapenia: Inactivity: Anabolic resistance: DietIn a recent consensus paper sarcopenia (1) was defined as the age-associated loss of skeletal muscle mass and function, a complex syndrome associated with muscle mass loss alone or in conjunction with increased fat mass. It was argued that although cachexia may be a component of sarcopenia, the two conditions are not the same. What was not discussed in this paper was the difference between sarcopenia and dynapenia which is important in terms of the clinical relevance of the condition. Thus Jansonn (2) points out that the data on the functional implications of sarcopenia are inconsistent, possibly because we do not always recognise the distinction between sarcopenia, loss of muscle mass and dynapenia and loss of muscle strength. These, he argues, are physiologically different with dynapenia the main predictor of functional impairment and/or physical disability, chronic disease and mortality risk, to the extent that research and clinical emphasis should be placed more on dynapenia than on sarcopenia. In fact this argument can, to some extent be extended to include frailty, a much more general term for a collection

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Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia

Abstract: At moderate availability, the effect of insulin on LPB is diminished in older human beings, and this effect may be mediated through blunted Akt-PKB activation.

Cited by 178 publications

References 34 publications

Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis

Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis

The muscle protein synthetic response to the combined ingestion of protein and carbohydrate is not impaired in healthy older men

Nutrition and sarcopenia: evidence for an interaction

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