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1.
Am J Physiol Endocrinol Metab ; 327(1): E42-E54, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38717363

RESUMEN

Skeletal muscle microvascular blood flow (MBF) plays an important role in glucose disposal in muscle. Impairments in muscle MBF contribute to insulin resistance and prediabetes. Animal studies show that short-term (3 day) high-fat feeding blunts skeletal muscle MBF before impairing insulin-stimulated glucose disposal. It is not known whether this occurs in humans. We investigated the temporal impact of a 7-day high-calorie high-fat (HCHF) diet intervention (+52% kJ; 41% fat) on fasting and postprandial cardiometabolic outcomes in 14 healthy adults (18-37 yr). Metabolic health and vascular responses to a mixed-meal challenge (MMC) were measured at pre (day 0)-, mid (day 4)- and post (day 8)-intervention. There were no significant differences in body weight, body fat %, fasting blood glucose, and fasting plasma insulin concentrations at pre-, mid- and postintervention. Compared with preintervention there was a significant increase in insulin (but not glucose) total area under the curve in response to the MMC at midintervention (P = 0.041) and at postintervention (P = 0.028). Unlike at pre- and midintervention, at postintervention muscle MBF decreased at 60 min (P = 0.024) and 120 min (P = 0.023) after the MMC. However, macrovascular blood flow was significantly increased from 0 to 60 min (P < 0.001) and 120 min (P < 0.001) after the MMC at pre-, mid- and postintervention. Therefore, short-term HCHF feeding in healthy individuals leads to elevated postprandial insulin but not glucose levels and a blunting of meal-induced skeletal muscle MBF responses but not macrovascular blood flow responses.NEW & NOTEWORTHY This is the first study to investigate skeletal muscle microvascular blood flow (MBF) responses in humans after short-term high-calorie high-fat (HCHF) diet. The main findings were that HCHF diet causes elevated postprandial insulin in healthy individuals within 3 days and blunts meal-induced muscle MBF within 7 days, despite no impairments in postprandial glucose or macrovascular blood flow.


Asunto(s)
Glucemia , Dieta Alta en Grasa , Hiperinsulinismo , Insulina , Músculo Esquelético , Periodo Posprandial , Humanos , Adulto , Masculino , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Adulto Joven , Femenino , Adolescente , Periodo Posprandial/fisiología , Insulina/sangre , Glucemia/metabolismo , Flujo Sanguíneo Regional , Microcirculación/fisiología , Resistencia a la Insulina/fisiología , Voluntarios Sanos , Microvasos , Ayuno
2.
Eur J Nutr ; 63(4): 1315-1327, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38409436

RESUMEN

PURPOSE: Evidence is growing that high salt intake is an independent risk factor for obesity, but the mechanisms are unknown. Our novel working hypothesis is that high salt intake drives cortisol production, which in turn, drives obesity. The current study aimed to demonstrate an acute cortisol response following a single high salt meal. METHODS: Eight participants (age 30.5 ± 9.8 years [mean ± SD], 50% female), consumed high salt (3.82 g; 1529 mg sodium) and low salt (0.02 g; 9 mg sodium) meals in a randomized cross-over design. RESULTS: Urinary and salivary cortisol and plasma adrenocorticotropic hormone (ACTH) demonstrated order effects. When high salt was given second, there was a peak above baseline for urinary cortisol (26.3%), salivary cortisol (9.4%) and plasma ACTH (4.1%) followed by a significant decline in each hormone (treatment*time, F[9, 18] = 2.641, p = 0.038, partial η2 = 0.569; treatment*time, F[12, 24] = 2.668, p = 0.020, partial η2 = 0.572; treatment*time, F[12, 24] = 2.580, p = 0.023, partial η2 = 0.563, respectively), but not when high salt was given first (p > 0.05 for all). CONCLUSION: These intriguing findings provide partial support for our hypothesis and support a need for further research to elucidate the role of high salt intake in cortisol production and, in turn, in the aetiology of obesity. TRIAL REGISTRATION NUMBER: ACTRN12623000490673; date of registration 12/05/2023; retrospectively registered.


Asunto(s)
Estudios Cruzados , Hidrocortisona , Obesidad , Cloruro de Sodio Dietético , Humanos , Hidrocortisona/sangre , Femenino , Proyectos Piloto , Adulto , Obesidad/metabolismo , Cloruro de Sodio Dietético/administración & dosificación , Masculino , Adulto Joven , Saliva/metabolismo , Hormona Adrenocorticotrópica/sangre
3.
Nutr Metab Cardiovasc Dis ; 33(4): 797-808, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36890071

RESUMEN

BACKGROUND AND AIMS: Individual dietary fats can differentially impact on cardiometabolic health. However, their impact within a dietary pattern is not well understood, and warrants comparison with diet quality scores with a dietary fat focus. The aim of this study was to investigate cross-sectional associations between a posteriori dietary patterns characterized by fat type and cardiometabolic health markers, and compare these with two diet quality scores. METHODS AND RESULTS: UK Biobank adults with ≥two 24-h dietary assessments and data on cardiometabolic health were included (n = 24 553; mean age: 55.9 y). A posteriori dietary patterns (DP1; DP2) were generated through reduced rank regression (response variables: SFA, MUFA, PUFA). Mediterranean Diet Score (MDS) and Dietary Approaches to Stop Hypertension (DASH) dietary patterns were created. Multiple linear regression analyses were used to investigate associations between standardized dietary patterns and cardiometabolic health (total cholesterol, HDL-C, LDL-C and VLDL-C cholesterol, triglycerides, C-reactive protein [CRP], glycated hemoglobin [HbA1c]). DP1, positively correlated with SFAs, MUFAs and PUFAs, characterized by higher nuts, seeds and vegetables intake and lower fruits and low-fat yoghurt intake, was associated with lower HDL-C (ß: -0.07; 95% CI: -0.10, -0.03) and triglycerides (-0.17; -0.23, -0.10) and higher LDL-C (0.07; 0.01,0.12), CRP (0.01; 0.01, 0.03) and HbA1c (0.16; 0.11,0.21). DP2, positively correlated with SFAs, negatively correlated with PUFAs, characterized by higher butter and high-fat cheese intake and lower nuts, seeds and vegetable intake, was associated with higher total cholesterol (0.10; 0.01, 0.21), VLDL-C (0.05; 0.02, 0.07), triglycerides (0.07; 0.01, 0.13), CRP (0.03; 0.02, 0,04) and HbA1c (0.06; 0.01, 0.11). Higher adherence to MDS and DASH was associated with favorable cardiometabolic health markers concentration. CONCLUSIONS: Irrespective of the method used, dietary patterns that encourage healthy fat consumption were associated with favorable cardiometabolic health biomarkers. This study strengthens the evidence for incorporation of dietary fat type into policy and practice guidelines for CVD prevention.


Asunto(s)
Enfermedades Cardiovasculares , Dieta Mediterránea , Adulto , Humanos , Persona de Mediana Edad , Hemoglobina Glucada , LDL-Colesterol , Estudios Transversales , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Grasas de la Dieta/efectos adversos , Triglicéridos , Ácidos Grasos Insaturados , Proteína C-Reactiva/metabolismo , Factores de Riesgo
4.
Diabetologia ; 65(1): 216-225, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34590175

RESUMEN

AIMS/HYPOTHESIS: Microvascular blood flow (MBF) increases in skeletal muscle postprandially to aid in glucose delivery and uptake in muscle. This vascular action is impaired in individuals who are obese or have type 2 diabetes. Whether MBF is impaired in normoglycaemic people at risk of type 2 diabetes is unknown. We aimed to determine whether apparently healthy people at risk of type 2 diabetes display impaired skeletal muscle microvascular responses to a mixed-nutrient meal. METHODS: In this cross-sectional study, participants with no family history of type 2 diabetes (FH-) for two generations (n = 18), participants with a positive family history of type 2 diabetes (FH+; i.e. a parent with type 2 diabetes; n = 16) and those with type 2 diabetes (n = 12) underwent a mixed meal challenge (MMC). Metabolic responses (blood glucose, plasma insulin and indirect calorimetry) were measured before and during the MMC. Skeletal muscle large artery haemodynamics (2D and Doppler ultrasound, and Mobil-O-graph) and microvascular responses (contrast-enhanced ultrasound) were measured at baseline and 1 h post MMC. RESULTS: Despite normal blood glucose concentrations, FH+ individuals displayed impaired metabolic flexibility (reduced ability to switch from fat to carbohydrate oxidation vs FH-; p < 0.05) during the MMC. The MMC increased forearm muscle microvascular blood volume in both the FH- (1.3-fold, p < 0.01) and FH+ (1.3-fold, p < 0.05) groups but not in participants with type 2 diabetes. However, the MMC increased MBF (1.9-fold, p < 0.01), brachial artery diameter (1.1-fold, p < 0.01) and brachial artery blood flow (1.7-fold, p < 0.001) and reduced vascular resistance (0.7-fold, p < 0.001) only in FH- participants, with these changes being absent in FH+ and type 2 diabetes. Participants with type 2 diabetes displayed significantly higher vascular stiffness (p < 0.001) compared with those in the FH- and FH+ groups; however, vascular stiffness did not change during the MMC in any participant group. CONCLUSIONS/INTERPRETATION: Normoglycaemic FH+ participants display impaired postprandial skeletal muscle macro- and microvascular responses, suggesting that poor vascular responses to a meal may contribute to their increased risk of type 2 diabetes. We conclude that vascular insulin resistance may be an early precursor to type 2 diabetes in humans, which can be revealed using an MMC.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Glucemia/metabolismo , Estudios Transversales , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Insulina/metabolismo , Músculo Esquelético/metabolismo , Padres , Periodo Posprandial
5.
J Physiol ; 600(7): 1667-1681, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35045191

RESUMEN

Insulin infusion increases skeletal muscle microvascular blood flow (MBF) in healthy people but is impaired during insulin resistance. However, we have shown that eliciting insulin secretion via oral glucose loading in healthy people impairs muscle MBF, whilst others have demonstrated intravenous glucose infusion stimulates MBF. We aimed to show that the route of glucose administration (oral versus intravenous) influences muscle MBF, and explore potential gut-derived hormones that may explain these divergent responses. Ten healthy individuals underwent a 120 min oral glucose tolerance test (OGTT; 75 g glucose) and on a subsequent occasion an intravenous glucose tolerance test (IVGTT, bypassing the gut) matched for similar blood glucose excursions. Femoral artery and thigh muscle microvascular (contrast-enhanced ultrasound) haemodynamics were measured at baseline and during the OGTT/IVGTT. Plasma insulin, C-peptide, glucagon, non-esterified fatty acids and a range of gut-derived hormones and incretins (gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1(GLP-1)) were measured at baseline and throughout the OGTT/IVGTT. The IVGTT increased whereas the OGTT impaired MBF (1.3-fold versus 0.5-fold from baseline, respectively, P = 0.0006). The impairment in MBF during the OGTT occurred despite producing 2.8-fold higher plasma insulin concentrations (P = 0.0001). The change in MBF from baseline (ΔMBF) negatively correlated with ΔGIP concentrations (r = -0.665, P < 0.0001). The natural log ratio of incretins GLP-1:GIP was positively associated with ΔMBF (r = 0.658, P < 0.0001), suggesting they have opposing actions on the microvasculature. Postprandial hyperglycaemia per se does not acutely determine opposing microvascular responses between OGTT and IVGTT. Incretins may play a role in modulating skeletal muscle MBF in humans. KEY POINTS: Insulin or mixed nutrient meals stimulate skeletal muscle microvascular blood flow (MBF) to aid in the delivery of nutrients; however, this vascular effect is lost during insulin resistance. Food/drinks containing large glucose loads impair MBF in healthy people; however, this impairment is not observed when glucose is infused intravenously (bypassing the gut). We investigated skeletal muscle MBF responses to a 75 g oral glucose tolerance test and intravenous glucose infusion and aimed to identify potential gut hormones responsible for glucose-mediated changes in MBF. Despite similar blood glucose concentrations, orally ingested glucose impaired, whereas intravenously infused glucose augmented, skeletal muscle MBF. The incretin gastric inhibitory polypeptide was negatively associated with MBF, suggestive of an incretin-mediated MBF response to oral glucose ingestion. This work provides new insight into why diets high in glucose may be detrimental to vascular health and provides new avenues for novel treatment strategies targeting microvascular dysfunction.


Asunto(s)
Glucosa , Incretinas , Glucemia , Polipéptido Inhibidor Gástrico/farmacología , Glucosa/farmacología , Humanos , Incretinas/farmacología , Insulina , Microcirculación , Músculo Esquelético
6.
Am J Physiol Endocrinol Metab ; 323(3): E319-E332, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35767699

RESUMEN

Osteoglycin (OGN) and lipocalin-2 (LCN2) are hormones that can be secreted by bone and have been linked to glucose homeostasis in rodents. However, the endocrine role of these hormones in humans is contradictory and unclear. We examined the effects of exercise and meal ingestion on circulating serum OGN and LCN2 levels in eight healthy males {age: 28 [25, 30] years [median ± interquartile range (IQR)] and body mass index [BMI]: 24.3 [23.6, 25.5] kg/m2}. In a randomized crossover design, participants ingested a high-glucose (1.1 g glucose/kg body wt) mixed-nutrient meal (45% carbohydrate, 20% protein, and 35% fat) on a rest-control day and 3 and 24 h after aerobic cycling exercise (1 h at 70%-75% V̇o2peak). Acute aerobic exercise increased serum LCN2 levels immediately after exercise (∼61%), which remained elevated 3-h postexercise (∼55%). In contrast, serum OGN remained similar to baseline levels throughout the 3-h postexercise recovery period. The ingestion of a high-glucose mixed-nutrient meal led to a decrease in serum OGN at 90-min (approximately -17%) and 120-min postprandial (approximately -44%), and a decrease in LCN2 at 120-min postprandial (approximately -26%). Compared with the control meal, prior exercise elevated serum OGN and LCN2 levels at 120-min postprandial when the meal was ingested 3-h (OGN: ∼74% and LCN2: ∼68%) and 24-h postexercise (OGN: ∼56% and LCN2: ∼16%). Acute exercise increases serum LCN2 and attenuates the postprandial decrease in OGN and LCN2 following high-glucose mixed-nutrient meal ingestion. The potential endocrine role of circulating OGN and LCN2 in humans warrants further investigation.NEW & NOTEWORTHY We provide novel evidence that OGN and LCN2 decrease 120 min after ingesting a high-glucose mixed-nutrient meal in healthy adults. Acute aerobic exercise increases circulating LCN2 for up to 3-h postexercise, whereas circulating OGN remains similar to baseline. Despite differing postexercise responses, postprandial LCN2 and OGN are elevated when the high-glucose meal is ingested 3-h and 24-h postexercise. Findings support that OGN and LCN2 are dynamically linked to energy homeostasis in humans.


Asunto(s)
Ejercicio Físico , Periodo Posprandial , Adulto , Glucemia/metabolismo , Ingestión de Alimentos , Ejercicio Físico/fisiología , Glucosa , Hormonas , Humanos , Insulina/metabolismo , Lipocalina 2 , Masculino , Nutrientes , Periodo Posprandial/fisiología
7.
Am J Physiol Endocrinol Metab ; 323(5): E418-E427, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35723226

RESUMEN

Adipose tissue microvascular blood flow (MBF) is stimulated postprandially to augment delivery of nutrients and hormones to adipocytes. Adipose tissue MBF is impaired in type 2 diabetes (T2D). Whether healthy individuals at-risk of T2D show similar impairments is unknown. We aimed to determine whether adipose tissue MBF is impaired in apparently healthy individuals with a family history of T2D. Overnight-fasted individuals with no family history of T2D for two generations (FH-, n = 13), with at least one parent with T2D (FH+, n = 14) and clinically diagnosed T2D (n = 11) underwent a mixed meal challenge (MMC). Metabolic responses [blood glucose, plasma insulin, plasma nonesterified fatty acids (NEFAs), and fat oxidation] were measured before and during the MMC. MBF in truncal subcutaneous adipose tissue was assessed by contrast ultrasound while fasting and 60 min post-MMC. FH+ had normal blood glucoses, increased adiposity, and impaired post-MMC adipose tissue MBF (Δ0.70 ± 0.22 vs. 2.45 ± 0.60 acoustic intensity/s, P = 0.007) and post-MMC adipose tissue insulin resistance (Adipo-IR index; Δ45.5 ± 13.9 vs. 7.8 ± 5.1 mmol/L × pmol/L, P = 0.007) compared with FH-. FH+ and T2D had an impaired ability to suppress fat oxidation post-MMC. Fat oxidation incremental area under the curve (iAUC) (35-55 min post-MMC, iAUC) was higher in FH+ and T2D than in FH- (P = 0.005 and 0.009, respectively). Postprandial MBF was negatively associated with postprandial fat oxidation iAUC (P = 0.01). We conclude that apparently healthy FH+ individuals display blunted postprandial adipose tissue MBF that occurs in parallel with adipose tissue insulin resistance and impaired suppression of fat oxidation, which may help explain their heightened risk for developing T2D.NEW & NOTEWORTHY Adipose tissue blood flow plays a key role in postprandial nutrient storage. People at-risk of type 2 diabetes have impaired postmeal adipose tissue blood flow. Impaired adipose tissue blood flow is associated with altered fat oxidation. Risk of type 2 diabetes may be elevated by poor adipose tissue blood flow.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Insulinas , Adulto , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Glucemia/metabolismo , Resistencia a la Insulina/fisiología , Microcirculación , Ácidos Grasos no Esterificados/metabolismo , Periodo Posprandial/fisiología , Tejido Adiposo/metabolismo , Nutrientes , Hormonas/metabolismo , Insulinas/metabolismo , Insulina/metabolismo
8.
FASEB J ; 35(5): e21499, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33811697

RESUMEN

The microvasculature is important for both health and exercise tolerance in a range of populations. However, methodological limitations have meant changes in microvascular blood flow are rarely assessed in humans during interventions designed to affect skeletal muscle blood flow such as the wearing of compression garments. The aim of this study is, for the first time, to use contrast-enhanced ultrasound to directly measure the effects of compression on muscle microvascular blood flow alongside measures of femoral artery blood flow and muscle oxygenation following intense exercise in healthy adults. It was hypothesized that both muscle microvascular and femoral artery blood flows would be augmented with compression garments as compared with a control condition. Ten recreationally active participants completed two repeated-sprint exercise sessions, with and without lower-limb compression tights. Muscle microvascular blood flow, femoral arterial blood flow (2D and Doppler ultrasound), muscle oxygenation (near-infrared spectroscopy), cycling performance, and venous blood samples were measured/taken throughout exercise and the 1-hour post-exercise recovery period. Compared with control, compression reduced muscle microvascular blood volume and attenuated the exercise-induced increase in microvascular velocity and flow immediately after exercise and 1 hour post-exercise. Compression increased femoral artery diameter and augmented the exercise-induced increase in femoral arterial blood flow during exercise. Markers of blood oxygen extraction in muscle were increased with compression during and after exercise. Compression had no effect on blood lactate, glucose, or exercise performance. We provide new evidence that lower-limb compression attenuates the exercise-induced increase in skeletal muscle microvascular blood flow following exercise, despite a divergent increase in femoral artery blood flow. Decreased muscle microvascular perfusion is offset by increased muscle oxygen extraction, a potential mechanism allowing for the maintenance of exercise performance.


Asunto(s)
Ejercicio Físico , Hemodinámica , Microcirculación , Músculo Esquelético/fisiología , Consumo de Oxígeno , Oxígeno/metabolismo , Flujo Sanguíneo Regional , Adulto , Estudios de Casos y Controles , Tolerancia al Ejercicio , Femenino , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagen , Perfusión , Ultrasonografía
9.
Scand J Med Sci Sports ; 32(7): 1076-1088, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35274374

RESUMEN

BACKGROUND: There is a universal need to increase the number of adults meeting physical activity (PA) recommendations to help improve health. In recent years, electrically assisted bicycles (e-bikes) have emerged as a promising method for supporting people to initiate and maintain physical activity levels. To the best of our knowledge, there have been no meta-analyses conducted to quantify the difference in physiological responses between e-cycling with electrical assistance, e-cycling without assistance, conventional cycling, and walking. METHODS: A systematic review and meta-analysis was conducted following PRISMA guidelines. We identified short-term e-bike studies, which utilized a crossover design comparing physiological outcomes when e-cycling with electrical assistance, e-cycling without electrical assistance, conventional cycling, or walking. Energy expenditure (EE), heart rate (HR), oxygen consumption (VO2 ), power output (PO), and metabolic equivalents (METs) outcomes were included within the meta-analysis. RESULTS: Fourteen studies met our inclusion criteria (N = 239). E-cycling with electrical assistance resulted in a lower energy expenditure (EE) [SMD = -0.46 (-0.98, 0.06), p = 0.08], heart rate (HR) [MD = -11.41 (-17.15, -5.68), p < 0.000, beats per minute], oxygen uptake (VO2 ) [SMD = -0.57 (-0.96, -0.17), p = 0.005], power output (PO) [MD = -31.19 (-47.19 to -15.18), p = 0.000, Watts], and metabolic equivalent (MET) response [MD = -0.83 (-1.52, -0.14), p = 0.02, METs], compared with conventional cycling. E-cycling with moderate electrical assistance resulted in a greater HR response [MD 10.38 (-1.48, 22.23) p = 0.09, beats per minute], and VO2 response [SMD 0.34 (-0.14, 0.82) p = 0.16] compared with walking. CONCLUSIONS: E-cycling was associated with increased physiological responses that can confer health benefits.


Asunto(s)
Ciclismo , Consumo de Oxígeno , Adulto , Ciclismo/fisiología , Metabolismo Energético/fisiología , Ejercicio Físico/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Consumo de Oxígeno/fisiología
10.
BMC Public Health ; 22(1): 2399, 2022 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-36544125

RESUMEN

BACKGROUND: Insufficient physical activity (PA) is a risk factor for the development of many non-communicable diseases. Electric bicycles (e-bikes) offer considerable potential to support people to be physically active, however, no previous e-bike intervention studies have supported e-bike use with behavioural support. The aim of this study was to co-develop theory-based intervention components which can be used to increase physical activity through e-cycling among people who are overweight or obese and physically inactive. METHODS: We conducted a mixed-methods study using an online survey and virtual co-design workshops. We utilised the Behaviour Change Wheel (BCW) to inform the development of the behavioural support intervention to facilitate day-to-day e-cycling. RESULTS: One hundred participants completed an online survey and seven participated in the online co-design workshops. The development of the intervention identified five intervention functions (enablement, training, environmental restructuring, education, and persuasion) and 16 behaviour change techniques (BCTs) from 11 BCT groups (goals and planning, feedback and monitoring, social support, shaping knowledge, natural consequences, comparison of behaviour, associations, repetition and substitution, comparison of outcomes, antecedents, and self-belief). CONCLUSION: To our knowledge, this is the first study to combine co-design and the BCW to develop a comprehensive behavioural support intervention for e-bike use. Theory based intervention options should be considered when providing e-bikes to individuals to help them increase their habitual PA levels.


Asunto(s)
Ciclismo , Ejercicio Físico , Humanos , Terapia Conductista , Promoción de la Salud/métodos , Australia
11.
J Physiol ; 599(1): 83-102, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33191527

RESUMEN

KEY POINTS: Exercise, insulin-infusion and low-glucose mixed-nutrient meal ingestion increases muscle microvascular blood flow which in part facilitates glucose delivery and disposal. In contrast, high-glucose ingestion impairs muscle microvascular blood flow which may contribute to impaired postprandial metabolism. We investigated the effects of prior cycling exercise on postprandial muscle microvascular blood flow responses to a high-glucose mixed-nutrient meal ingested 3 and 24 h post-exercise. Prior exercise enhanced muscle microvascular blood flow and mitigated microvascular impairments induced by a high-glucose mixed meal ingested 3 h post-exercise, and to a lesser extent 24 h post-exercise. High-glucose ingestion 3 h post-exercise leads to greater postprandial blood glucose, non-esterified fatty acids, and fat oxidation, and a delay in the insulin response to the meal compared to control. Effects of acute exercise on muscle microvascular blood flow persist well after the cessation of exercise which may be beneficial for conditions characterized by microvascular and glycaemic dysfunction. ABSTRACT: Exercise, insulin-infusion and low-glucose mixed-nutrient meal ingestion lead to increased muscle microvascular blood flow (MBF), whereas high-glucose ingestion impairs MBF. We investigated whether prior cycling exercise could enhance postprandial muscle MBF and prevent MBF impairments induced by high-glucose mixed-nutrient meal ingestion. In a randomized cross-over design, eight healthy young men ingested a high-glucose mixed-nutrient meal (1.1 g glucose/kg body weight; 45% carbohydrate, 20% protein and 35% fat) after an overnight fast (no-exercise control) and 3 h and 24 h after moderate-intensity cycling exercise (1 h at 70-75% V̇O2peak ). Skeletal muscle MBF, measured directly by contrast-enhanced ultrasound, was lower at 60 min and 120 min postprandially compared to baseline in all conditions (P < 0.05), with a greater decrease occurring from 60 min to 120 min in the control (no-exercise) condition only (P < 0.001). Despite this meal-induced decrease, MBF was still markedly higher compared to control in the 3 h post-exercise condition at 0 min (pre-meal; 74%, P = 0.004), 60 min (112%, P = 0.002) and 120 min (223%, P < 0.001), and in the 24 h post-exercise condition at 120 min postprandially (132%, P < 0.001). We also report that in the 3 h post-exercise condition postprandial blood glucose, non-esterified fatty acids (NEFAs), and fat oxidation were substantially elevated, and the insulin response to the meal delayed compared to control. This probably reflects a combination of increased post-exercise exogenous glucose appearance, substrate competition, and NEFA-induced insulin resistance. We conclude that prior cycling exercise elicits long-lasting effects on muscle MBF and partially mitigates MBF impairments induced by high-glucose mixed-nutrient meal ingestion.


Asunto(s)
Glucemia , Microcirculación , Músculo Esquelético , Glucemia/metabolismo , Glucosa , Humanos , Insulina/metabolismo , Masculino , Periodo Posprandial
12.
J Nutr ; 151(11): 3570-3578, 2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-34522964

RESUMEN

BACKGROUND: The fat type consumed is considered a risk factor for developing obesity and type 2 diabetes (T2D). However, these associations have not been investigated using a dietary patterns approach, which can capture combinations of foods and fat type consumed. OBJECTIVES: This study aimed to investigate associations between dietary patterns with varying proportions of SFAs, MUFAs, or PUFAs and obesity, abdominal obesity, and self-reported T2D incidence. METHODS: This study included UK Biobank participants with 2 or more 24-h dietary assessments, free from the outcome of interest at recruitment, and with outcome data at follow-up (n = 16,523; mean follow-up: 6.3 y). Reduced rank regression was used to derive dietary patterns with SFAs, MUFAs, and PUFAs (% of energy intake) as response variables. Logistic regression, adjusted for sociodemographic and health characteristics, was used to investigate the associations between dietary patterns and obesity [BMI (kg/m2) ≥30], abdominal obesity (waist circumference; men: ≥102 cm; women: ≥88 cm) and T2D incidence. RESULTS: Two dietary patterns, DP1 and DP2, were identified: DP1 positively correlated with SFAs (r = 0.48), MUFAs (r = 0.67), and PUFAs (r = 0.56), characterized by higher intake of nuts, seeds, and butter and lower intake of fruit and low-fat yogurt; DP2 positively correlated with SFAs (r = 0.76) and negatively with PUFAs (r = -0.64) and MUFAs (r = -0.01), characterized by higher intake of butter and high-fat cheese and lower intake of nuts and seeds. Only DP2 was associated with higher obesity and abdominal obesity incidence (OR: 1.24; 95% CI: 1.02, 1.45; and OR: 1.19; 95% CI: 1.02, 1.38, respectively). Neither of the dietary patterns was associated with T2D incidence. CONCLUSIONS: These findings provide evidence that a dietary pattern characterized by higher SFA and lower PUFA foods is associated with obesity and abdominal obesity incidence, but not T2D.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Bancos de Muestras Biológicas , Diabetes Mellitus Tipo 2/epidemiología , Grasas de la Dieta , Ácidos Grasos , Femenino , Humanos , Estudios Longitudinales , Masculino , Obesidad/epidemiología , Reino Unido/epidemiología
13.
Am J Physiol Endocrinol Metab ; 318(6): E1014-E1021, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32286881

RESUMEN

Oral glucose ingestion leads to impaired muscle microvascular blood flow (MBF), which may contribute to acute hyperglycemia-induced insulin resistance. We investigated whether incorporating lipids and protein into a high-glucose load would prevent postprandial MBF dysfunction. Ten healthy young men (age, 27 yr [24, 30], mean with lower and upper bounds of the 95% confidence interval; height, 180 cm [174, 185]; weight, 77 kg [70, 84]) ingested a high-glucose (1.1 g/kg glucose) mixed-nutrient meal (10 kcal/kg; 45% carbohydrate, 20% protein, and 35% fat) in the morning after an overnight fast. Femoral arterial blood flow was measured via Doppler ultrasound, and thigh MBF was measured via contrast-enhanced ultrasound, before meal ingestion and 1 h and 2 h postprandially. Blood glucose and plasma insulin were measured at baseline and every 15 min throughout the 2-h postprandial period. Compared with baseline, thigh muscle microvascular blood volume, velocity, and flow were significantly impaired at 60 min postprandial (-25%, -27%, and -46%, respectively; all P < 0.05) and to a greater extent at 120 min postprandial (-37%, -46%, and -64%; all P < 0.01). Heart rate and femoral arterial diameter, blood velocity, and blood flow were significantly increased at 60 min and 120 min postprandial (all P < 0.05). Higher blood glucose area under the curve was correlated with greater MBF dysfunction (R2 = 0.742; P < 0.001). Ingestion of a high-glucose mixed-nutrient meal impairs MBF in healthy individuals for up to 2 h postprandial.


Asunto(s)
Glucemia/metabolismo , Arteria Femoral/fisiopatología , Glucosa/administración & dosificación , Hiperglucemia/fisiopatología , Insulina/metabolismo , Microcirculación/fisiología , Músculo Esquelético/irrigación sanguínea , Flujo Sanguíneo Regional/fisiología , Adulto , Velocidad del Flujo Sanguíneo/fisiología , Arteria Femoral/diagnóstico por imagen , Voluntarios Sanos , Frecuencia Cardíaca/fisiología , Humanos , Hiperglucemia/diagnóstico por imagen , Masculino , Comidas , Músculo Esquelético/diagnóstico por imagen , Periodo Posprandial , Muslo , Ultrasonografía , Adulto Joven
14.
Clin Exp Pharmacol Physiol ; 47(3): 520-528, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31702069

RESUMEN

The matching of capillary blood flow to metabolic rate of the cells within organs and tissues is a critical microvascular function which ensures appropriate delivery of hormones and nutrients, and the removal of waste products. This relationship is particularly important in tissues where local metabolism, and hence capillary blood flow, must be regulated to avoid a mismatch between nutrient demand and supply that would compromise normal function. The consequences of a mismatch in microvascular blood flow and metabolism are acutely apparent in the brain and heart, where a sudden cessation of blood flow, for example following an embolism, acutely manifests as stroke or myocardial infarction. Even in more resilient tissues such as skeletal muscle, a short-term mismatch reduces muscle performance and exercise tolerance, and can cause intermittent claudication. In the longer-term, a microvascular-metabolic mismatch in skeletal muscle reduces insulin-mediated muscle glucose uptake, leading to disturbances in whole-body metabolic homeostasis. While the notion that capillary blood flow is fine-tuned to meet cellular metabolism is well accepted, the mechanisms that control this function and where and how different parts of the vascular tree contribute to capillary blood flow regulation remain poorly understood. Here, we discuss the emerging evidence implicating pericytes, mural cells that surround capillaries, as key mediators that match tissue metabolic demand with adequate capillary blood flow in a number of organs, including skeletal muscle.


Asunto(s)
Capilares/metabolismo , Microcirculación/fisiología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Pericitos/metabolismo , Flujo Sanguíneo Regional/fisiología , Animales , Capilares/citología , Metabolismo Energético/fisiología , Humanos , Músculo Esquelético/citología
15.
Clin Exp Pharmacol Physiol ; 47(4): 725-737, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31868941

RESUMEN

Skeletal muscle contributes to ~40% of total body mass and has numerous important mechanical and metabolic roles in the body. Skeletal muscle is a major site for glucose disposal following a meal. Consequently, skeletal muscle plays an important role in postprandial blood glucose homeostasis. Over the past number of decades, research has demonstrated that insulin has an important role in vasodilating the vasculature in skeletal muscle in response to an insulin infusion (hyperinsulinaemic-euglycaemic clamp) or following the ingestion of a meal. This vascular action of insulin is pivotal for glucose disposal in skeletal muscle, as insulin-stimulated vasodilation increases the delivery of both glucose and insulin to the myocyte. Notably, in insulin-resistant states such as obesity and type 2 diabetes, this vascular response of insulin in skeletal muscle is significantly impaired. Whereas the majority of work in this field has focussed on the action of insulin alone on skeletal muscle microvascular blood flow and myocyte glucose metabolism, there is less understanding of how the consumption of a meal may affect skeletal muscle blood flow. This is in part due to complex variations in glucose and insulin dynamics that occurs postprandially-with changes in humoral concentrations of glucose, insulin, amino acids, gut and pancreatic peptides-compared to the hyperinsulinaemic-euglycaemic clamp. This review will address the emerging body of evidence to suggest that postprandial blood flow responses in skeletal muscle may be a function of the nutritional composition of a meal.


Asunto(s)
Técnica de Clampeo de la Glucosa , Hiperinsulinismo/fisiopatología , Microcirculación , Músculo Esquelético/fisiopatología , Periodo Posprandial , Animales , Humanos , Hiperinsulinismo/sangre
16.
Am J Physiol Endocrinol Metab ; 315(2): E307-E315, 2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29763373

RESUMEN

Skeletal muscle microvascular (capillary) blood flow increases in the postprandial state or during insulin infusion due to dilation of precapillary arterioles to augment glucose disposal. This effect occurs independently of changes in large artery function. However, acute hyperglycemia impairs vascular function, causes insulin to vasoconstrict precapillary arterioles, and causes muscle insulin resistance in vivo. We hypothesized that acute hyperglycemia impairs postprandial muscle microvascular perfusion, without disrupting normal large artery hemodynamics, in healthy humans. Fifteen healthy people (5 F/10 M) underwent an oral glucose challenge (OGC, 50 g glucose) and a mixed-meal challenge (MMC) on two separate occasions (randomized, crossover design). At 1 h, both challenges produced a comparable increase (6-fold) in plasma insulin levels. However, the OGC produced a 1.5-fold higher increase in blood glucose compared with the MMC 1 h postingestion. Forearm muscle microvascular blood volume and flow (contrast-enhanced ultrasound) were increased during the MMC (1.3- and 1.9-fold from baseline, respectively, P < 0.05 for both) but decreased during the OGC (0.7- and 0.6-fold from baseline, respectively, P < 0.05 for both) despite a similar hyperinsulinemia. Both challenges stimulated brachial artery flow (ultrasound) and heart rate to a similar extent, as well as yielding comparable decreases in diastolic blood pressure and total vascular resistance. Systolic blood pressure and aortic stiffness remained unaltered by either challenge. Independently of large artery hemodynamics, hyperglycemia impairs muscle microvascular blood flow, potentially limiting glucose disposal into skeletal muscle. The OGC reduced microvascular blood flow in muscle peripherally and therefore may underestimate the importance of skeletal muscle in postprandial glucose disposal.


Asunto(s)
Glucosa/farmacología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/efectos de los fármacos , Administración Oral , Adolescente , Adulto , Arterias/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Estudios Transversales , Femenino , Antebrazo/irrigación sanguínea , Voluntarios Sanos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hiperglucemia/metabolismo , Hiperglucemia/fisiopatología , Hiperinsulinismo/sangre , Masculino , Microcirculación/efectos de los fármacos , Persona de Mediana Edad , Flujo Sanguíneo Regional/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos , Adulto Joven
17.
Am J Physiol Endocrinol Metab ; 315(6): E1242-E1250, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-30351988

RESUMEN

The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favorable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7 women/11 men, 52 ± 7 yr) completed 6 wk of RT. Before and after RT, overnight-fasted participants had blood sampled for clinical chemistries (glucose, insulin, lipids, HbA1c, and proinflammatory markers) and underwent an oral glucose challenge (OGC; 50 g glucose × 2 h) and a DEXA scan to assess body composition. Adipose tissue microvascular blood volume and flow were assessed at rest and 1 h post-OGC using contrast-enhanced ultrasound. RT significantly reduced fasting blood glucose ( P = 0.006), HbA1c ( P = 0.007), 2-h glucose area under the time curve post-OGC ( P = 0.014), and homeostatic model assessment of insulin resistance ( P = 0.005). This was accompanied by a small reduction in total body fat ( P = 0.002), trunk fat ( P = 0.023), and fasting triglyceride levels ( P = 0.029). Lean mass ( P = 0.003), circulating TNF-α ( P = 0.006), and soluble VCAM-1 ( P < 0.001) increased post-RT. There were no significant changes in adipose tissue microvascular blood volume or flow following RT; however those who did have a higher baseline microvascular blood flow post-RT also had lower fasting triglyceride levels ( r = -0.476, P = 0.045). The anthropometric, glycemic, and insulin-sensitizing benefits of 6 wk of RT in people with T2D are not associated with an improvement in adipose tissue microvascular responses; however, there may be an adipose tissue microvascular-linked benefit to fasting triglyceride levels.


Asunto(s)
Tejido Adiposo/irrigación sanguínea , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Microvasos/fisiología , Flujo Sanguíneo Regional/fisiología , Entrenamiento de Fuerza , Absorciometría de Fotón , Glucemia/metabolismo , Composición Corporal , Femenino , Humanos , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad
18.
Am J Physiol Heart Circ Physiol ; 315(5): H1425-H1433, 2018 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30095999

RESUMEN

Peripheral arterial disease (PAD) is characterized by stenosis and occlusion of the lower limb arteries. Although leg blood flow is limited in PAD, it remains unclear whether skeletal muscle microvascular perfusion is affected. We compared whole leg blood flow and calf muscle microvascular perfusion after cuff occlusion and submaximal leg exercise between patients with PAD ( n = 12, 69 ± 9 yr) and healthy age-matched control participants ( n = 12, 68 ± 7 yr). Microvascular blood flow (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after the following: 1) 5 min of thigh-cuff occlusion, and 2) a 5-min bout of intermittent isometric plantar-flexion exercise (400 N) using real-time contrast-enhanced ultrasound. Whole leg blood flow was measured after thigh-cuff occlusion and during submaximal plantar-flexion exercise using strain-gauge plethysmography. Postocclusion whole leg blood flow and calf muscle microvascular perfusion were lower in patients with PAD than control participants, and these parameters were strongly correlated ( r = 0.84, P < 0.01). During submaximal exercise, total whole leg blood flow and vascular conductance were not different between groups. There were also no group differences in postexercise calf muscle microvascular perfusion, although microvascular blood volume was higher in patients with PAD than control participants (12.41 ± 6.98 vs. 6.34 ± 4.98 arbitrary units, P = 0.03). This study demonstrates that the impaired muscle perfusion of patients with PAD during postocclusion hyperemia is strongly correlated with disease severity and is likely mainly determined by the limited conduit artery flow. In response to submaximal leg exercise, microvascular flow volume was elevated in patients with PAD, which may reflect a compensatory mechanism to maintain muscle perfusion and oxygen delivery during recovery from exercise. NEW & NOTEWORTHY This study suggests that peripheral arterial disease (PAD) has different effects on the microvascular perfusion responses to cuff occlusion and submaximal leg exercise. Patients with PAD have impaired microvascular perfusion after cuff occlusion, similar to that previously reported after maximal exercise. In response to submaximal exercise, however, the microvascular flow volume response was elevated in patients with PAD compared with control. This finding may reflect a compensatory mechanism to maintain perfusion and oxygen delivery during recovery from exercise.


Asunto(s)
Tolerancia al Ejercicio , Claudicación Intermitente/fisiopatología , Microcirculación , Músculo Esquelético/irrigación sanguínea , Enfermedad Arterial Periférica/fisiopatología , Anciano , Índice Tobillo Braquial , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Medios de Contraste/administración & dosificación , Prueba de Esfuerzo , Femenino , Fluorocarburos/administración & dosificación , Humanos , Claudicación Intermitente/diagnóstico por imagen , Contracción Isométrica , Extremidad Inferior , Masculino , Microburbujas , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico por imagen , Flujo Sanguíneo Regional , Oclusión Terapéutica , Ultrasonografía Doppler
19.
Clin Exp Pharmacol Physiol ; 44(1): 143-149, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27797410

RESUMEN

Skeletal muscle is an important site for insulin to regulate blood glucose levels. It is estimated that skeletal muscle is responsible for ~80% of insulin-mediated glucose disposal in the post-prandial period. The classical action of insulin to increase muscle glucose uptake involves insulin binding to insulin receptors on myocytes to stimulate glucose transporter 4 (GLUT 4) translocation to the cell surface membrane, enhancing glucose uptake. However, an additional role of insulin that is often under-appreciated is its action to increase muscle perfusion thereby improving insulin and glucose delivery to myocytes. Either of these responses (myocyte and/or vascular) may be impaired in insulin resistance, and both impairments are apparent in type 2 diabetes, resulting in diminished glucose disposal by muscle. The aim of this review is to report on the growing body of literature suggesting that insulin-mediated control of skeletal muscle perfusion is an important regulator of muscle glucose uptake and that impairment of microvascular insulin action has important physiological consequences early in the pathogenesis of insulin resistance. This work was discussed at the 2015 Australian Physiological Society Symposium "Physiological mechanisms controlling microvascular flow and muscle metabolism".


Asunto(s)
Resistencia a la Insulina/fisiología , Microcirculación/fisiología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Flujo Sanguíneo Regional/fisiología , Animales , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Humanos
20.
J Physiol ; 594(8): 2223-31, 2016 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-25581640

RESUMEN

Insulin resistance plays a key role in the development of type 2 diabetes. Skeletal muscle is the major storage site for glucose following a meal and as such has a key role in maintenance of blood glucose concentrations. Insulin resistance is characterised by impaired insulin-mediated glucose disposal in skeletal muscle. Multiple mechanisms can contribute to development of muscle insulin resistance and our research has demonstrated an important role for loss of microvascular function within skeletal muscle. We have shown that insulin can enhance blood flow to the microvasculature in muscle thus improving the access of glucose and insulin to the myocytes to augment glucose disposal. Obesity, insulin resistance and ageing are all associated with impaired microvascular responses to insulin in skeletal muscle. Impairments in insulin-mediated microvascular perfusion in muscle can directly cause insulin resistance, and this event can occur early in the aetiology of this condition. Understanding the mechanisms involved in the loss of microvascular function in muscle has the potential to identify novel treatment strategies to prevent or delay progression of insulin resistance and type 2 diabetes.


Asunto(s)
Envejecimiento/metabolismo , Resistencia a la Insulina , Microvasos/metabolismo , Músculo Esquelético/irrigación sanguínea , Envejecimiento/fisiología , Animales , Humanos , Microcirculación , Microvasos/fisiología , Músculo Esquelético/metabolismo
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