Plasma 25-hydroxyvitamin D is related to protein signaling involved in glucose homeostasis in a tissue-specific manner

Vitamin D has been suggested to play a role in glucose metabolism. However, previous findings are contradictory and mechanistic pathways remain unclear. We examined the relationship between plasma 25-hydroxyvitamin D (25(OH)D), insulin sensitivity, and insulin signaling in skeletal muscle and adipose tissue. Seventeen healthy adults (Body mass index: 26 ± 4; Age: 30 ± 12 years) underwent a hyperinsulinemic-euglycemic clamp, and resting skeletal muscle and adipose tissue biopsies. In this cohort, the plasma 25(OH)D concentration was not associated with insulin sensitivity (r = 0.19, p = 0.56). However, higher plasma 25(OH)D concentrations correlated with lower phosphorylation of glycogen synthase kinase-3 (GSK-3) αSer21 and βSer9 in skeletal muscle (r = −0.66, p = 0.015 and r = −0.53, p = 0.06, respectively) and higher GSK-3 αSer21 and βSer9 phosphorylation in adipose tissue (r = 0.82, p < 0.01 and r = 0.62, p = 0.042, respectively). Furthermore, higher plasma 25(OH)D concentrations were associated with greater phosphorylation of both protein kinase-B (AktSer473) (r = 0.78, p < 0.001) and insulin receptor substrate-1 (IRS-1Ser312) (r = 0.71, p = 0.01) in adipose tissue. No associations were found between plasma 25(OH)D concentration and IRS-1Tyr612 phosphorylation in skeletal muscle and adipose tissue. The divergent findings between muscle and adipose tissue with regard to the association between 25(OH)D and insulin signaling proteins may suggest a tissue-specific interaction with varying effects on glucose homeostasis. Further research is required to elucidate the physiological relevance of 25(OH)D in each tissu

PO-265 Acute whole-body vibration increases energy expenditure and skeletal muscle microvascular perfusion

Objective Insulin resistance and cardiometabolic disease are associated with decreased muscle microvascular perfusion which impairs nutrient delivery to the muscle.&nbsp; Impaired glucose and insulin delivery contributes to lower glucose uptake into the skeletal muscle. Exercise increases muscle microvascular perfusion, however, cardiometabolic disease patients are not always willing or able to undertake regular exercise. Objective: Whole-body vibration (WBV) has previously been shown to increase energy expenditure and limb bulk blood flow, however whether WBV increases skeletal muscle microvascular perfusion is not known.&nbsp;&nbsp; Methods Methods: Eleven healthy participants (5 males, 6 females; Age: 33 ± 1.9 years) stood on a WBV platform (Galileo Sport, Novotec Medical GmbH, Pforzheim, Germany) for 3 min at 12.5 Hz which was compared to standing without vibration.&nbsp; Thigh muscle (vastus lateralis) microvascular perfusion was assessed by contrast-enhanced ultrasound (iU22, Philips Medical, North Ryde, NSW, Australia) by infusing Definity® microbubbles (Lantheus Medical Imaging, N. Billeruca, USA) intravenously and measured for 3 min following WBV.&nbsp; Oxygen consumption (Metamax, Cortex Biophysik GmbH, Leipzig, Germany) was measured while standing prior to WBV and during the third minute of WBV. Results Results: Compared with standing without vibration, 3 min of WBV more than doubled muscle microvascular perfusion (0.73 ± 0.17 vs 2.87 ± 0.81 AI/sec, p&lt;0.05) which remained elevated above baseline for 3 min after cessation of WBV. Oxygen consumption modestly but significantly increased while undergoing WBV (282 ± 0.013 vs 419 ± 0.023 mL/min, p&lt;0.05). Conclusions Conclusion: This is the first study to show that WBV significantly increases muscle microvascular perfusion in healthy adults. &nbsp;We are currently undertaking studies to determine if this WBV may be of benefit in populations with impaired microvascular perfusion, such as type 2 diabetes, for improving cardiometabolic health. &nbsp

Acute high-intensity interval exercise-induced redox signaling is associated with enhanced insulin sensitivity in obese middle-aged men

Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1–3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation (r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion: These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE

Exercise and glycemic control: focus on redox homeostasis and redox-sensitive protein signaling

Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis.<br /

The effect of exercise-intensity on skeletal muscle stress kinase and insulin protein signaling

Background: Stress and mitogen activated protein kinase (SAPK) signaling play an important role in glucose homeostasis and the physiological adaptation to exercise. However, the effects of acute high-intensity interval exercise (HIIE) and sprint interval exercise (SIE) on activation of these signaling pathways are unclear. Methods: Eight young and recreationally active adults performed a single cycling session of HIIE (5&times;4 minutes at 75% Wmax), SIE (4 &times; 30 second Wingate sprints), and continuous moderate-intensity exercise work-matched to HIIE (CMIE; 30 minutes at 50% of Wmax), separated by a minimum of 1 week. Skeletal muscle SAPK and insulin protein signaling were measured immediately, and 3 hours after exercise. Results: SIE elicited greater skeletal muscle NF-&kappa;B p65 phosphorylation immediately after exercise (SIE: &sim;40%; HIIE: &sim;4%; CMIE; &sim;13%; p &lt; 0.05) compared to HIIE and CMIE. AS160Ser588 phosphorylation decreased immediately after HIIE (&sim;-27%; p &lt; 0.05), and decreased to the greatest extent immediately after SIE (&sim;-60%; p &lt; 0.05). Skeletal muscle JNK (&sim;42%; p &lt; 0.05) and p38 MAPK (&sim;171%; p &lt; 0.05) phosphorylation increased, and skeletal muscle AktSer473 phosphorylation (&sim;-32%; p &lt; 0.05) decreased, to a similar extent immediately after all exercise protocols. AS160Ser588 phosphorylation was similar to baseline three hours after SIE (&sim;-12%; p &gt; 0.05), remained lower 3 hours after HIIE (&sim;-34%; p &lt; 0.05), and decreased 3 hours after CMIE (&sim;-33%; p &lt; 0.05). Conclusion: Despite consisting of less total work than CMIE and HIIE, SIE proved to be an effective stimulus for the activation of stress protein kinase signaling pathways linked to exercise-mediated adaptation of skeletal muscle. Furthermore, post-exercise AS160Ser588 phosphorylation decreased in an exercise-intensity and post-exercise time-course dependent manner

The Effects of Acute High-Intensity Interval Exercise and Hyperinsulinemic-Euglycemic Clamp on Osteoglycin Levels in Young and Middle-Aged Men

Osteoglycin (OGN) is a leucine-rich proteoglycan that has been implicated in the regulation of glucose in animal models. However, its relationship with glucose control in humans is unclear. We examined the effect of high-intensity interval exercise (HIIE) and hyperinsulinemic-euglycemic clamp on circulating levels of OGN as well as whether circulating OGN levels are associated with markers of glycemic control and cardio-metabolic health. Serum was analyzed for OGN (ELISA) levels from 9 middle-aged obese men (58.1 ± 2.2 years, body mass index [BMI] = 33.1 ± 1.4 kg∙m−2, mean ± SEM) and 9 young men (27.8 ± 1.6 years, BMI = 24.4 ± 0.08 kg∙m−2) who previously completed a study involving a euglycemic-hyperinsulinemic clamp at rest and after HIIE (4x4 minutes cycling at approximately 95% peak heart rate (HRpeak), interspersed with 2 minutes of active recovery). Blood pressure, body composition (dual-energy X-ray absorptiometry), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed. Serum OGN was higher in the young cohort compared with the middle-aged cohort (65.2 ± 10.1 ng/mL versus 36.5 ± 4. 5 ng/mL, p ≤ 0.05). Serum OGN was unaffected by acute HIIE but decreased after the insulin clamp compared with baseline (~−27%, p = 0.01), post-exercise (~−35%, p = 0.01), and pre-clamp (~−32%, p = 0.02) time points, irrespective of age. At baseline, lower circulating OGN levels were associated with increased age, BMI, and fat mass, whereas higher OGN levels were related to lower fasting glucose. Higher OGN levels were associated with a higher glucose infusion rate. Exercise had a limited effect on circulating OGN. The mechanisms by which OGN affects glucose regulation should be explored in the future. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research

Exploring the feasibility of a 6-week electric-bike intervention with behavioural support in Australia.

Background: Physical inactivity increases the risk of non-communicable disease development and healthcare-associated burden. Research suggests electric bikes (e-bikes) can support individuals in meeting recommended physical activity (PA) guidelines. This study assessed the feasibility of an e-bike plus a tailored behavioural support intervention for physically inactive overweight or obese adults. Methods: This non-randomized single-group pre-post study saw participants provided with an e-bike free of charge for six weeks. Feasibility was assessed across five domains: 1) feasibility of recruitment, 2) participant retention, 3) intervention adherence, 4) acceptability of questionnaires and lab-based outcome measures and 5) intervention acceptability. Participants completed self-reported measures of PA and self-efficacy for exercise. Lab-based measurements were completed pre-and post-intervention, this included blood pressure, body composition [anthropometrics and dual-energy X-ray absorptiometry (DEXA)], venous blood glucose, insulin, cholesterol, triglycerides, and cardiorespiratory fitness. Results: Our recruitment strategy saw a total of eight participants (three males and five females) complete the intervention (88.9% retention rate). Participants utilised the e-bike for the intervention duration and rode a mean distance of 299.8 km (SD ± 172.2) over the 6-week intervention period. Participants completed all outcomes with minimal data points missing. Participants’ moderate PA levels and self-efficacy for exercise increased post intervention. Lab-based measures showed a downward trend in body fat percentage, fasting blood glucose and brachial diastolic blood pressure. Conclusion: The recruitment strategy, retention, adherence and acceptability of this study support future research. E-bikes are an acceptable way to help people who are physically inactive increase their PA levels. Furthermore, sustained use may contribute to health benefits and improve overall self-efficacy for exercise

The effects of acute high-intensity interval exercise and hyperinsulinemic-euglycemic clamp on osteoglycin levels in young and middle-aged men

Osteoglycin (OGN) is a leucine-rich proteoglycan that has been implicated in the regulation of glucose in animal models. However, its relationship with glucose control in humans is unclear. We examined the effect of high-intensity interval exercise (HIIE) and hyperinsulinemic-euglycemic clamp on circulating levels of OGN as well as whether circulating OGN levels are associated with markers of glycemic control and cardio-metabolic health. Serum was analyzed for OGN (ELISA) levels from 9 middle-aged obese men (58.1 ± 2.2 years, body mass index [BMI] = 33.1 ± 1.4 kg∙m − 2, mean ± SEM) and 9 young men (27.8 ± 1.6 years, BMI = 24.4 ± 0.08 kg∙m − 2) who previously completed a study involving a euglycemic-hyperinsulinemic clamp at rest and after HIIE (4 x 4 minutes cycling at approximately 95% peak heart rate (HRpeak), interspersed with 2 minutes of active recovery). Blood pressure, body composition (dual-energy X-ray absorptiometry), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed. Serum OGN was higher in the young cohort compared with the middle-aged cohort (65.2 ± 10.1 ng/mL versus 36.5 ± 4. 5 ng/mL, p ≤ 0.05). Serum OGN was unaffected by acute HIIE but decreased after the insulin clamp compared with baseline (~ − 27 %, p = 0.01), post-exercise (~ − 35 %, p = 0.01), and pre-clamp (~ − 32 %, p = 0.02) time points, irrespective of age. At baseline, lower circulating OGN levels were associated with increased age, BMI, and fat mass, whereas higher OGN levels were related to lower fasting glucose. Higher OGN levels were associated with a higher glucose infusion rate. Exercise had a limited effect on circulating OGN. The mechanisms by which OGN affects glucose regulation should be explored in the future

Acute HIIE elicits similar changes in human skeletal muscle mitochondrial H2O2 release, respiration, and cell signaling as endurance exercise even with less work

It remains unclear whether high-intensity interval exercise (HIIE) elicits distinct molecular responses to traditional endurance exercise relative to the total work performed. We aimed to investigate the influence of exercise intensity on acute perturbations to skeletal muscle mitochondrial function (respiration and reactive oxygen species) and metabolic and redox signaling responses. In a randomized, repeated measures crossover design, eight recreationally active individuals (24 ± 5 yr; V̇O2peak: 48 ± 11 ml·kg−1·min−1) undertook continuous moderate-intensity [CMIE: 30 min, 50% peak power output (PPO)], high-intensity interval (HIIE: 5 × 4 min, 75% PPO, work matched to CMIE), and low-volume sprint interval (SIE: 4 × 30 s) exercise, ≥7 days apart. Each session included muscle biopsies at baseline, immediately, and 3 h postexercise for high-resolution mitochondrial respirometry (JO2) and H2O2 emission (JH2O2) and gene and protein expression analysis. Immediately postexercise and irrespective of protocol, Jo2 increased during complex I + II leak/state 4 respiration but JH2O2 decreased (P < 0.05). AMP-activated protein kinase and acetyl co-A carboxylase phosphorylation increased ~1.5 and 2.5-fold respectively, while thioredoxin-reductase-1 protein abundance was ~35% lower after CMIE vs. SIE (P < 0.05). At 3 h postexercise, regardless of protocol, JO2 was lower during both ADP-stimulated state 3 OXPHOS and uncoupled respiration (P < 0.05) but JH2O2 trended higher (P < 0.08) and PPARGC1A mRNA increased ~13-fold, and peroxiredoxin-1 protein decreased ~35%. In conclusion, intermittent exercise performed at high intensities has similar dynamic effects on muscle mitochondrial function compared with endurance exercise, irrespective of whether total workload is matched. This suggests exercise prescription can accommodate individual preferences while generating comparable molecular signals known to promote beneficial metabolic adaptations