Acute exercise and high-glucose ingestion elicit dynamic and individualized responses in systemic markers of redox homeostasis.

Background: Biomarkers of oxidation-reduction (redox) homeostasis are commonly measured in human blood to assess whether certain stimuli (e.g., high-glucose ingestion or acute exercise) lead to a state of oxidative distress (detrimental to health) or oxidative eustress (beneficial to health). Emerging research indicates that redox responses are likely to be highly individualized, yet few studies report individual responses. Furthermore, the effects of complex redox stimuli (e.g., high-glucose-ingestion after exercise) on redox homeostasis remains unclear. We investigated the effect of acute exercise (oxidative eustress), high-glucose ingestion (oxidative distress), and high-glucose ingestion after exercise (both oxidative eu/distress), on commonly measured redox biomarkers in serum/plasma. Methods: In a randomized crossover fashion, eight healthy men (age: 28 ± 4 years; BMI: 24.5 ± 1.5 kg/m2 [mean ± SD]) completed two separate testing conditions; 1) consumption of a high-glucose mixed-nutrient meal (45% carbohydrate [1.1 g glucose.kg-1], 20% protein, and 35% fat) at rest (control trial), and 2) consumption of the same meal 3 h and 24 h after 1 h of moderate-intensity cycling exercise (exercise trial). Plasma and serum were analyzed for an array of commonly studied redox biomarkers. Results: Oxidative stress and antioxidant defense markers (hydrogen peroxide, 8-isoprostanes, catalase, superoxide dismutase, and nitrate levels) increased immediately after exercise (p < 0.05), whereas nitric oxide activity and thiobarbituric acid reactive substances (TBARS) remained similar to baseline (p > 0.118). Nitric oxide activity and nitrate levels decreased at 3 h post-exercise compared to pre-exercise baseline levels. Depending on when the high-glucose mixed nutrient meal was ingested and the postprandial timepoint investigated, oxidative stress and antioxidant defense biomarkers either increased (hydrogen peroxide, TBARS, and superoxide dismutase), decreased (hydrogen peroxide, 8-isoprostanes, superoxide dismutase, nitric oxide activity, nitrate, and nitrite), or remained similar to pre-meal baseline levels (hydrogen peroxide, 8-isoprostanes, TBARS, catalase, superoxide dismutase and nitrite). Redox responses exhibited large inter-individual variability in the magnitude and/or direction of responses. Conclusion: Findings highlight the necessity to interpret redox biomarkers in the context of the individual, biomarker measured, and stimuli observed. Individual redox responsiveness may be of physiological relevance and should be explored as a potential means to inform personalized redox intervention.

Prior aerobic exercise mitigates the decrease in serum osteoglycin and lipocalin-2 following high-glucose mixed-nutrient meal ingestion in young men.

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.

Prior exercise enhances skeletal muscle microvascular blood flow and mitigates microvascular flow impairments induced by a high-glucose mixed meal in healthy young men.

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.

High-glucose mixed-nutrient meal ingestion impairs skeletal muscle microvascular blood flow in healthy young men.

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.

Modest changes to glycemic regulation are sufficient to maintain glucose fluxes in healthy young men following overfeeding with a habitual macronutrient composition.

Currently, it is unclear whether short-term overfeeding in healthy people significantly affects postprandial glucose regulation, as most human overfeeding studies have utilized induced experimental conditions such as the euglycemic-hyperinsulinemic clamp technique to assess glucoregulation. The aim of this study was to quantify glucose fluxes [rates of meal glucose appearance (Ra), disposal (Rd), and endogenous glucose production (EGP)] in response to 5 and 28 days of overfeeding (+45% energy) while maintaining habitual macronutrient composition (31.0 ± 1.9% fat, 48.6 ± 2.2% carbohydrate, 16.7 ± 1.4% protein) in healthy, lean young men. Meal tolerance testing was combined with the triple-stable isotope glucose tracer approach. Visceral adipose volume increased by ~15% with 5 days of overfeeding, while there was no further change at 28 days. In contrast, body mass (+1.6 kg) and fat mass (+1.3 kg) were significantly increased only after 28 days of overfeeding. Fasting EGP, Rd, and insulin were increased at 5 but unchanged after 28 days. Postprandial glucose and insulin responses were unaltered by 5 days of overfeeding but were modestly increased after 28 days (P < 0.05). However, meal Ra and glucose Rd were significantly increased after both 5 and 28 days of overfeeding (P < 0.05). Despite this, overfeeding did not lead to alterations to postprandial EGP suppression. Thus, in contrast to findings from euglycemic-hyperinsulinemic clamp studies, chronic overfeeding did not affect the ability to suppress EGP or stimulate Rd under postprandial conditions. Rather, glucose flux was appropriately maintained following 28 days of overfeeding through modest increases in postprandial glycemia and insulinemia.

Measurement of postprandial glucose fluxes in response to acute and chronic endurance exercise in healthy humans.

The effect of endurance exercise on enhancing insulin sensitivity and glucose flux has been well established with techniques such as the hyperinsulinemic clamp. Although informative, such techniques do not emulate the physiological postprandial state, and it remains unclear how exercise improves postprandial glycaemia. Accordingly, combining mixed-meal tolerance testing and the triple-stable isotope glucose tracer approach, glucose fluxes [rates of meal glucose appearance (Ra), disposal (Rd), and endogenous glucose production (EGP)] were determined following acute endurance exercise (1 h cycling; ~70% V̇o2max) and 4 wk of endurance training (cycling 5 days/wk). Training was associated with a modest increase in V̇o2max (~7%, P < 0.001). Postprandial glucose and insulin responses were reduced to the same extent following acute and chronic training. Interestingly, this was not accompanied by changes to rates of meal Ra, Rd, or degree of EGP suppression. Glucose clearance (Rd relative to prevailing glucose) was, however, enhanced with acute and chronic exercise. Furthermore, the duration of EGP suppression was shorter with acute and chronic exercise, with EGP returning toward fasting levels more rapidly than pretraining conditions. These findings suggest that endurance exercise influences the efficiency of the glucoregulatory system, where pretraining rates of glucose disposal and production were achieved at lower glucose and insulin levels. Notably, there was no influence of chronic training over and above that of a single exercise bout, providing further evidence that glucoregulatory benefits of endurance exercise are largely attributed to the residual effects of the last exercise bout.