Muscle microvascular blood flow responses in insulin resistance and ageing

Keske, Michelle A.; Premilovac, Dino; Bradley, EA; Dwyer, RM; Richards, Stephen M.; Rattigan, Stephen

doi:10.1113/jphysiol.2014.283549

Cited by 57 publications

(86 citation statements)

References 65 publications

(146 reference statements)

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“…Similar results were obtained for metabolic syndrome and type-2-diabetes as age-related conditions [35–39], supporting a novel ‘vascular paradigm’ of insulin resistance, i.e. an attenuation of insulin-mediated recruitment of capillary exchange surface and transendothelial insulin transport as rate limiting steps for insulin (and glucose) delivery to skeletal muscle [36, 39–45]. Regarding exercise-induced microvascular response, human studies are limited to patients with diabetic microangiopathy [46].…”

Section: Introductionsupporting

confidence: 83%

Age-related differences in skeletal muscle microvascular response to exercise as detected by contrast-enhanced ultrasound (CEUS)

et al. 2017

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BackgroundAging involves reductions in exercise total limb blood flow and exercise capacity. We hypothesized that this may involve early age-related impairments of skeletal muscle microvascular responsiveness as previously reported for insulin but not for exercise stimuli in humans.MethodsUsing an isometric exercise model, we studied the effect of age on contrast-enhanced ultrasound (CEUS) parameters, i.e. microvascular blood volume (MBV), flow velocity (MFV) and blood flow (MBF) calculated from replenishment of Sonovue contrast-agent microbubbles after their destruction. CEUS was applied to the vastus lateralis (VLat) and intermedius (VInt) muscle in 15 middle-aged (MA, 43.6±1.5 years) and 11 young (YG, 24.1±0.6 years) healthy males before, during, and after 2 min of isometric knee extension at 15% of peak torque (PT). In addition, total leg blood flow as recorded by femoral artery Doppler-flow. Moreover, fiber-type-specific and overall capillarisation as well as fiber composition were additionally assessed in Vlat biopsies obtained from CEUS site. MA and YG had similar quadriceps muscle MRT-volume or PT and maximal oxygen uptake as well as a normal cardiovascular risk factors and intima-media-thickness.ResultsDuring isometric exercise MA compared to YG reached significantly lower levels in MFV (0.123±0.016 vs. 0.208±0.036 a.u.) and MBF (0.007±0.001 vs. 0.012±0.002 a.u.). In the VInt the (post-occlusive hyperemia) post-exercise peaks in MBV and MBF were significantly lower in MA vs. YG. Capillary density, capillary fiber contacts and femoral artery Doppler were similar between MA and YG.ConclusionsIn the absence of significant age-related reductions in capillarisation, total leg blood flow or muscle mass, healthy middle-aged males reveal impaired skeletal muscle microcirculatory responses to isometric exercise. Whether this limits isometric muscle performance remains to be assessed.

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Section: Introductionsupporting

confidence: 83%

Age-related differences in skeletal muscle microvascular response to exercise as detected by contrast-enhanced ultrasound (CEUS)

et al. 2017

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“…) and humans (reviewed by Keske et al . , in this issue). These increases are important, as they are part of the redistribution of the fuels that are absorbed with each of the main meals and therefore play an important role in the delivery of glucose, insulin and fatty acids to skeletal muscle as the main storage site.…”

Section: Introductionmentioning

confidence: 81%

“… and Keske et al . ). This suggests that the postprandial redistribution of the blood flow to skeletal muscle and potentially subcutaneous adipose tissue is reduced or absent in obese, elderly and insulin‐resistant individuals.…”

Section: Introductionmentioning

confidence: 97%

Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: effect of obesity and ageing

Wagenmakers

Strauss

Shepherd

et al. 2015

The Journal of Physiology

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This review concludes that a sedentary lifestyle, obesity and ageing impair the vasodilator response of the muscle microvasculature to insulin, exercise and VEGF-A and reduce microvascular density. Both impairments contribute to the development of insulin resistance, obesity and chronic age-related diseases. A physically active lifestyle keeps both the vasodilator response and microvascular density high. Intravital microscopy has shown that microvascular units (MVUs) are the smallest functional elements to adjust blood flow in response to physiological signals and metabolic demands on muscle fibres. The luminal diameter of a common terminal arteriole (TA) controls blood flow through up to 20 capillaries belonging to a single MVU. Increases in plasma insulin and exercise/muscle contraction lead to recruitment of additional MVUs. Insulin also increases arteriolar vasomotion. Both mechanisms increase the endothelial surface area and therefore transendothelial transport of glucose, fatty acids (FAs) and insulin by specific transporters, present in high concentrations in the capillary endothelium. Future studies should quantify transporter concentration differences between healthy and at risk populations as they may limit nutrient supply and oxidation in muscle and impair glucose and lipid homeostasis. An important recent discovery is that VEGF-B produced by skeletal muscle controls the expression of FA transporter proteins in the capillary endothelium and thus links endothelial FA uptake to the oxidative capacity of skeletal muscle, potentially preventing lipotoxic FA accumulation, the dominant cause of insulin resistance in muscle fibres.

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“…Reductions in vascular function in response to aging and/or diabetes may be due in part to reductions in NO synthesis and a reduced NO-mediated vasodilatory response to feeding-induced hyperinsulinemia (24). Consequently, a reduction in NO-mediated vascular function may attenuate postprandial plasma amino acid delivery to tissues, thereby having a negative impact on normal feeding-mediated increases in postprandial muscle protein synthesis rates.…”

Section: Discussionmentioning

confidence: 99%

“…However, aging and insulin resistance are associated with reduced skeletal muscle capillary density, impaired endothelial function, and reduced nitric oxide (NO) availability (14,20,32,39,40). As such, age-related impairments in vascular function due to an impaired NO-mediated vasodilatory response and decreased muscle tissue perfusion may diminish feeding-mediated increases in muscle protein synthesis and, thus, contribute to the anabolic resistance of aging (7,24).It has been reported that dietary nitrate (NO 3 Ϫ ) supplementation, via sequential reduction of NO 3 Ϫ to nitrite (NO 2 Ϫ ) and NO, can stimulate NO synthesis and increase NO bioavailability (55). Moreover, it has been suggested that NO has a role in promoting insulin delivery to skeletal muscle tissue and increasing insulin-stimulated muscle perfusion and capillary action (22, 51).…”

mentioning

confidence: 99%

Sodium nitrate co-ingestion with protein does not augment postprandial muscle protein synthesis rates in older, type 2 diabetes patients

Kouw

Cermak

Burd

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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13 C]leucine-labeled protein with (PRONO3) or without (PRO) sodium nitrate (0.15 mmol/kg). Blood and muscle samples were collected to assess protein digestion and absorption kinetics and postprandial muscle protein synthesis rates. Upon protein ingestion, exogenous phenylalanine appearance rates increased in both groups (P Ͻ 0.001), resulting in 55 Ϯ 2% and 53 Ϯ 2% of dietary protein-derived amino acids becoming available in the circulation over the 5h postprandial period in the PRO and PRONO3 groups, respectively. Postprandial myofibrillar protein synthesis rates based on L-[ring-2 H5]phenylalanine did not differ between groups (0.025 Ϯ 0.004 and 0.021 Ϯ 0.007%/h over 0 -2 h and 0.032 Ϯ 0.004 and 0.030 Ϯ 0.003%/h over 2-5 h in PRO and PRONO3, respectively, P ϭ 0.7). No differences in incorporation of dietary protein-derived L-[1-13 C]phenylalanine into de novo myofibrillar protein were observed at 5 h (0.016 Ϯ 0.002 and 0.014 Ϯ 0.002 mole percent excess in PRO and PRONO3, respectively, P ϭ 0.8). Dietary nitrate co-ingestion with protein does not modulate protein digestion and absorption kinetics, nor does it further increase postprandial muscle protein synthesis rates or the incorporation of dietary protein-derived amino acids into de novo myofibrillar protein in older, type 2 diabetes patients. dietary nitrate; protein ingestion; aging; type 2 diabetes; anabolic resistance AGING IS ASSOCIATED with loss of skeletal muscle mass and strength, termed sarcopenia, and results in loss of functional capacity, a higher risk for hospitalization, and development of chronic metabolic diseases (33). Recently, we (20, 31), as well as others (25,35), showed that sarcopenia is more pronounced in older individuals with type 2 diabetes than in age-matched, normoglycemic controls. Since skeletal muscle tissue is a large site of postprandial glucose disposal, it is evident that the age-related loss of skeletal muscle mass is often accompanied by an insulin-resistant state (20,31,35).Maintenance of skeletal muscle mass is regulated by muscle protein synthesis and muscle protein breakdown rates. A chronic imbalance between muscle protein synthesis and muscle protein breakdown rates contributes to the accelerated loss of skeletal muscle mass with aging. It has been well established that protein ingestion and the associated increase in postprandial plasma amino acids in the circulation directly increase muscle protein synthesis rates (15,26,34,50). However, the postprandial stimulation of muscle protein synthesis following protein intake is impaired with aging, a phenomenon commonly referred to as anabolic resistance (15). This anabolic resistance to protein intake is considered to be a key factor in the progressive loss of skeletal muscle mass with aging. Although the factor(s) underpinning anabolic resistance remains unclear, age-related impairments in endothelium-dependent vasodilation and blood flow in response to nutrient (32) and exercise (19) stimuli are suggested to play a key role.The postprandial muscle protein synthetic re...

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Muscle microvascular blood flow responses in insulin resistance and ageing

Cited by 57 publications

References 65 publications

Age-related differences in skeletal muscle microvascular response to exercise as detected by contrast-enhanced ultrasound (CEUS)

Age-related differences in skeletal muscle microvascular response to exercise as detected by contrast-enhanced ultrasound (CEUS)

Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: effect of obesity and ageing

Sodium nitrate co-ingestion with protein does not augment postprandial muscle protein synthesis rates in older, type 2 diabetes patients

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