Development of microdialysis methodology for interstitial insulin measurement in rodents.

INTRODUCTION: Accurate assessment of muscle insulin sensitivity requires measurement of insulin concentration in interstitial fluid (ISF), but has proved difficult. We aimed to optimise measurement of ISF insulin concentrations in rat muscles in vivo using microdialysis. METHODS: Factorial experimental design experiments were performed in vitro to determine optimal conditions for insulin recovery with microdialysis probes. These conditions were tested in vivo, adjusted appropriately and used in lean and obese Zucker rats to compare ISF insulin concentrations basally and during hyperinsulinaemic-euglycaemic (HE) clamp. RESULTS: Optimal conditions in vivo were: a 100kDa microdialysis probe inserted in muscle, perfused with 1% BSA, 1.5mM glucose in 0.9% sodium chloride at 1μl/min. Samples were collected into siliconised glass microvials. As a reference for insulin, we established a protocol of inulin infusion, beginning at -80min and reaching equilibrium within 60min. HE clamp, beginning at 0min, increased ISF insulin concentration from 122±56 basally to 429±180pmol/l (P<0.05) in lean rats and from 643±165 to 1087±243pmol/l (P=0.07) in obese rats; ISF insulin concentrations were significantly higher throughout in obese rats. The difference between ISF and plasma insulin concentration (ISF:plasma ratio) was substantially higher in obese rats, but fell to similar values in obese and lean rats during HE clamp. DISCUSSION: Optimising insulin recovery with microdialysis allowed accurate measurement of basal ISF insulin in muscle of lean and obese Zucker rats and indicates insulin transport across capillaries is impaired in obese rats, basally and during hyperinsulinaemia

Intrinsic motivation in two exercise interventions: Associations with fitness and body composition.

OBJECTIVE: To examine the motivational process through which increases in aerobic capacity and decreases in total body fat are achieved during high-intensity intermittent training (HIT) and moderate-intensity continuous training (MICT) interventions. METHOD: Eighty-seven physically inactive adults (65% women, age = 42 ± 12, BMI = 27.67 ± 4.99 kg/m2) took part in a 10-week randomized intervention testing group-based HIT, operationalized as repeated sprints of 15-60 s interspersed with periods of recovery cycling ≤ 25 min/session, 3 sessions/wk-1, or MICT, operationalized as cycling at constant workload of ∼65% maximum aerobic capacity (VO2max, 30-45 min/session-1, 5 sessions/wk-1. Assessments of VO2max and total body fat were made pre- and postintervention. Motivation variables were assessed midintervention and class attendance was monitored throughout. Path analysis was employed, controlling for treatment arm and baseline values of VO2max and total body fat. RESULTS: The 2 groups differed in adherence only, favoring HIT. Baseline VO2max predicted intrinsic motivation midintervention. Intrinsic motivation predicted program adherence, which in turn predicted increases in VO2max and decreases in total body fat by the end of the study. CONCLUSION: Intrinsic motivation in HIT and MICT is positively linked to adherence to these programs, which can facilitate improvements in fitness and body composition. (PsycINFO Database Recor

Neutrophil and Monocyte Bactericidal Responses to 10 Weeks of Low-Volume High-Intensity Interval or Moderate-Intensity Continuous Training in Sedentary Adults.

Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on immune function in sedentary adults. Twenty-seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO2peak), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function

Sprint interval and moderate-intensity continuous training have equal benefits on aerobic capacity, insulin sensitivity, muscle capillarisation and endothelial eNOS/NAD(P)Hoxidase protein ratio in obese men

Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), leading to similar improvements in skeletal muscle capillary density and microvascular function in young healthy humans. In this study we made the first comparisons of the muscle microvascular response to SIT and MICT in an obese population. Sixteen young obese men (age 25±1 yr, BMI 34.8±0.9 kg.m-2) were randomly assigned to 4 weeks of MICT (40-60 min cycling at ~65% VO2peak, 5 times per wk.) or constant load SIT (4-7 constant workload intervals of 200% Wattmax 3 times per wk.). Muscle biopsies were taken before and after training from the m. vastus lateralis to measure muscle microvascular endothelial eNOS content, eNOS serine1177 phosphorylation, NOX2 content and capillarization using quantitative immunofluorescence microscopy. Maximal aerobic capacity (VO2peak), whole body insulin sensitivity and arterial stiffness were also assessed. SIT and MICT increased skeletal muscle microvascular eNOS content and eNOS ser1177 phosphorylation in terminal arterioles and capillaries (P<0.05), but the later effect was eliminated when normalised to eNOS content (P = 0.217). SIT and MICT also reduced microvascular endothelial NOX2 content (P<0.05) and both increased capillary density and capillary-fibre-perimeter exchange index (P<0.05). In parallel, SIT and MICT increased VO2peak (P<0.05), whole body insulin sensitivity (P<0.05) and reduced central artery stiffness (P<0.05). As no significant differences were observed between SIT and MICT it is concluded that SIT is a time efficient alternative to MICT to improve aerobic capacity, insulin sensitivity and muscle capillarisation and endothelial eNOS/NAD(P)Hoxidase protein ratio in young obese men

Lipid droplet remodelling and reduced muscle ceramides following sprint interval and moderate-intensity continuous exercise training in obese males.

BACKGROUND: In obesity, improved muscle insulin sensitivity following exercise training has been linked to the lowering of diacylglycerol (DAG) and ceramide concentrations. Little is known, however, about how improved insulin action with exercise training in obese individuals relates to lipid droplet (LD) adaptations in skeletal muscle. In this study we investigated the hypothesis that short-term sprint interval training (SIT) and moderate intensity continuous training (MICT) in obese individuals would increase perilipin (PLIN) expression, increase the proportion of LDs in contact with mitochondria and reduce muscle concentrations of DAGs and ceramides. METHODS: Sixteen sedentary obese males performed 4 weeks of either SIT (4-7 × 30 s sprints at 200% Wmax, 3 days.week(-1)) or MICT (40-60 min cycling at ~65% VO2peak, 5 days.week(-1)), and muscle biopsies were obtained pre- and post-training. RESULTS: Training increased PLIN2 (SIT 90%, MICT 68%) and PLIN5 (SIT 47%, MICT 34%) expression in type I fibres only, and increased PLIN3 expression in both type I (SIT 63%, MICT 67%) and type II fibres (SIT 70%, MICT 160%) (all P<0.05). Training did not change LD content but increased the proportion of LD in contact with mitochondria (SIT 12%, MICT 21%, P<0.01). Ceramides were reduced following training (SIT -10%, MICT -7%, P<0.05), but DAG was unchanged. No training × group interactions were observed for any variables. CONCLUSIONS: These results confirm the hypothesis that SIT and MICT results in remodelling of LDs and lowers ceramide concentrations in skeletal muscle of sedentary obese males.International Journal of Obesity accepted article preview online, 24 July 2017. doi:10.1038/ijo.2017.170

Home-based high-intensity interval training reduces barriers to exercise in people with type 1 diabetes

People with type 1 diabetes (T1D) are recommended to engage in regular exercise for a variety of health and fitness reasons. However, many lead a sedentary lifestyle and fail to meet the physical activity guidelines, in part because of the challenge of managing blood glucose concentration and fear of hypoglycaemia. A number of strategies designed to help people with T1D to manage their blood glucose during and after exercise have been investigated. Although many of these strategies show promise in facilitating blood glucose management during and after exercise, they do not target the many other common barriers to exercise that people with T1D face, such as difficulty with cost and travel time to gyms, limited access to exercise bikes and treadmills, and a possible dislike of exercising in front of others in public places. In this symposium review, we provide an overview of ongoing research into a virtually monitored home‐based high‐intensity interval training (Home‐HIT) programme that is designed to reduce these other common barriers to exercise. The conclusion of this review is that Home‐HIT seems to offer a strategy to reduce fear of hypoglycaemia, while simultaneously removing other known barriers preventing people with T1D from taking up exercise, such as being time efficient, requiring no travel time or costs associated with gym memberships, and giving them the opportunity to exercise in their chosen environment, reducing the embarrassment experienced by some when exercising in public

Vascular health in patients in remission of Cushing's syndrome is comparable to that in BMI-matched controls.

CONTEXT: In active Cushing's syndrome (CS), patients suffer from endothelial dysfunction and premature atherosclerosis. However, it is uncertain to what extent vascular health recovers after long-term remission. This is highly relevant as this topic relates to future development of cardiovascular disease. OBJECTIVE: To investigate whether micro- and macrovascular health is impaired after long-term remission of CS, in patients with no or adequately treated co-morbidities. DESIGN AND SETTING: Cross-sectional case-control study in two tertiary referral centers. PATIENTS AND MAIN OUTCOME MEASURES: 63 patients (remission of CS for ≥ 4 years) and 63 healthy, well-matched controls were compared. In group A (58 patients and 58 controls) serum biomarkers associated with endothelial dysfunction, intima media thickness, pulse wave velocity and pulse wave analysis were studied. In group B (14 patients and 14 controls) endothelium-dependent and-independent vasodilatation was studied in conduit arteries (flow mediated dilation of the brachial artery) and forearm skeletal muscle resistance arteries (vasodilator response to intra-arterial acetylcholine, sodium-nitroprusside and N(G)-monomethyl-L-arginine using venous occlusion plethysmography). RESULTS: There were no significant differences between the outcome measures of vascular health of patients and controls in group A and B. CONCLUSION: Vascular health of patients in long-term remission of Cushing's syndrome seems to be comparable to that of healthy gender-, age and BMI matched controls, provided that the patients have no, or adequately controlled co-morbidities. Therefore, the effects of hypercortisolism per se on the vasculature may be reversible. This accentuates the need for stringent treatment of metabolic co-morbidities in these patients

Carbohydrate Restriction in Type 1 Diabetes: A Realistic Therapy for Improved Glycaemic Control and Athletic Performance?

Around 80% of individuals with Type 1 diabetes (T1D) in the United States do not achieve glycaemic targets and the prevalence of comorbidities suggests that novel therapeutic strategies, including lifestyle modification, are needed. Current nutrition guidelines suggest a flexible approach to carbohydrate intake matched with intensive insulin therapy. These guidelines are designed to facilitate greater freedom around nutritional choices but they may lead to higher caloric intakes and potentially unhealthy eating patterns that are contributing to the high prevalence of obesity and metabolic syndrome in people with T1D. Low carbohydrate diets (LCD; <130 g/day) may represent a means to improve glycaemic control and metabolic health in people with T1D. Regular recreational exercise or achieving a high level of athletic performance is important for many living with T1D. Research conducted on people without T1D suggests that training with reduced carbohydrate availability (often termed "train low") enhances metabolic adaptation compared to training with normal or high carbohydrate availability. However, these "train low" practices have not been tested in athletes with T1D. This review aims to investigate the known pros and cons of LCDs as a potentially effective, achievable, and safe therapy to improve glycaemic control and metabolic health in people with T1D. Secondly, we discuss the potential for low, restricted, or periodised carbohydrate diets in athletes with T1D

Association between atherogenic risk-modulating proteins and endothelium-dependent flow-mediated dilation in coronary artery disease patients

Purpose: Endothelial dysfunction is an early and integral event in the development of atherosclerosis and coronary artery disease (CAD). Reduced NO bioavailability, oxidative stress, vasoconstriction, inflammation and senescence are all implicated in endothelial dysfunction. However, there are limited data examining associations between these pathways and direct in vivo bioassay measures of endothelial function in CAD patients. This study aimed to examine the relationships between in vivo measures of vascular function and the expression of atherogenic risk-modulating proteins in endothelial cells (ECs) isolated from the radial artery of CAD patients. Methods: Fifty-six patients with established CAD underwent trans-radial catheterization. Prior to catheterization, radial artery vascular function was assessed using a) flow-mediated dilation (FMD), and b) exercise-induced dilation in response to handgrip (HE%). Freshly isolated ECs were obtained from the radial artery during catheterization and protein content of eNOS, NAD(P)H oxidase subunit NOX2, NFκB, ET-1 and the senescence markers p53, p21 and p16 were evaluated alongside nitrotyrosine abundance and eNOS Ser1177 phosphorylation. Results: FMD was positively associated with eNOS Ser1177 phosphorylation (r = 0.290, P = 0.037), and protein content of p21 (r = 0.307, P = 0.027) and p16 (r = 0.426, P = 0.002). No associations were found between FMD and markers of oxidative stress, vasoconstriction or inflammation. In contrast to FMD, HE% was not associated with any of the EC proteins. Conclusion: These data revealed a difference in the regulation of endothelium-dependent vasodilation measured in vivo between patients with CAD compared to previously reported data in subjects without a clinical diagnosis, suggesting that eNOS Ser1177 phosphorylation may be the key to maintain vasodilation in CAD patients

“Girls Aren’t Meant to Exercise”: Perceived Influences on Physical Activity among Adolescent Girls—The HERizon Project

Background. Adolescent girls are less active than boys, with approximately 10% of girls in Ireland and the United Kingdom meeting the minimum recommended daily physical activity (PA) guidelines. This study investigated factors perceived to influence PA among adolescent girls from low socioeconomic areas in order to inform the design of a future intervention (The HERizon Project). Methods. A total of 48 adolescent girls (13–18 years) from low socioeconomic areas of the United Kingdom and Ireland participated in focus groups (n = 8), to explore perspectives of physical activity and the influence of gender within this. Focus groups were thematically analyzed and interpreted within a socioecological framework. Results. Most girls enjoyed PA and were aware of its benefits. They identified both barriers and facilitators to PA at intrapersonal (fear of judgement and changing priorities WITH age), interpersonal (changing social pressures and support from others) and organizational (delivery of PE) levels. Gender inequality was a multilevel factor, crossing all socioecological levels. Conclusion. Although many adolescent girls enjoy PA, their experiences appear to be limited by a fear of judgement and an overarching sense of gender inequality. Future interventions, such as the HERizon Project, should address influences at intrapersonal, interpersonal and organizational levels to promote positive PA experiences for adolescent girls