One-year unsupervised individualized exercise training intervention enhances cardiorespiratory fitness but not muscle deoxygenation or glycemic control in adults with type 1 diabetes

Adaptations to long-term exercise training in type 1 diabetes are sparsely studied. We examined the effects of a 1-year individualized training intervention on cardiorespiratory fitness, exercise-induced active muscle deoxygenation, and glycemic control in adults with and without type 1 diabetes. Eight men with type 1 diabetes (T1D) and 8 healthy men (CON) matched for age, anthropometry, and peak pulmonary O-2 uptake, completed a 1-year individualized training intervention in an unsupervised real-world setting. Before and after the intervention, the subjects performed a maximal incremental cycling test, during which alveolar gas exchange (volume turbine and mass spectrometry) and relative concentration changes in active leg muscle deoxygenated (Delta[HHb]) and total (Delta[tHb]) hemoglobin (near-infrared spectroscopy) were monitored. Peak O-2 pulse, reflecting peak stroke volume, was calculated (peak pulmonary O-2 uptake/peak heart rate). Glycemic control (glycosylated hemoglobin A(1c) (HbA(1c))) was evaluated. Both T1D and CON averagely performed 1 resistance-training and 3-4 endurance-training sessions per week (similar to 1 h/session at similar to moderate intensity). Training increased peak pulmonary O-2 uptake in T1D (p = 0.004) and CON (p = 0.045) (group x time p = 0.677). Peak O-2 pulse also rose in T1D (p = 0.032) and CON (p = 0.018) (group x time p = 0.880). Training increased leg Delta[HHb] at peak exercise in CON (p = 0.039) but not in T1D (group x time p = 0.052), while no changes in leg Delta[tHb] at any work rate were observed in either group (p > 0.05). HbA(1c) retained unchanged in T1D (from 58 +/- 10 to 59 +/- 11 mmol/mol, p = 0.609). In conclusion, 1-year adherence to exercise training enhanced cardiorespiratory fitness similarly in T1D and CON but had no effect on active muscle deoxygenation or glycemic control in T1D.Peer reviewe

Alveolar gas exchange and tissue oxygenation during incremental treadmill exercise, and their associations with blood O(2) carrying capacity

The magnitude and timing of oxygenation responses in highly active leg muscle, less active arm muscle, and cerebral tissue, have not been studied with simultaneous alveolar gas exchange measurement during incremental treadmill exercise. Nor is it known, if blood O(2) carrying capacity affects the tissue-specific oxygenation responses. Thus, we investigated alveolar gas exchange and tissue (m. vastus lateralis, m. biceps brachii, cerebral cortex) oxygenation during incremental treadmill exercise until volitional fatigue, and their associations with blood O(2) carrying capacity in 22 healthy men. Alveolar gas exchange was measured, and near-infrared spectroscopy (NIRS) was used to monitor relative concentration changes in oxy- (Δ[O(2)Hb]), deoxy- (Δ[HHb]) and total hemoglobin (Δ[tHb]), and tissue saturation index (TSI). NIRS inflection points (NIP), reflecting changes in tissue-specific oxygenation, were determined and their coincidence with ventilatory thresholds [anaerobic threshold (AT), respiratory compensation point (RC); V-slope method] was examined. Blood O(2) carrying capacity [total hemoglobin mass (tHb-mass)] was determined with the CO-rebreathing method. In all tissues, NIPs coincided with AT, whereas RC was followed by NIPs. High tHb-mass associated with leg muscle deoxygenation at peak exercise (e.g., Δ[HHb] from baseline walking to peak exercise vs. tHb-mass: r = 0.64, p < 0.01), but not with arm muscle- or cerebral deoxygenation. In conclusion, regional tissue oxygenation was characterized by inflection points, and tissue oxygenation in relation to alveolar gas exchange during incremental treadmill exercise resembled previous findings made during incremental cycling. It was also found out, that O(2) delivery to less active m. biceps brachii may be limited by an accelerated increase in ventilation at high running intensities. In addition, high capacity for blood O(2) carrying was associated with a high level of m. vastus lateralis deoxygenation at peak exercise.Peer reviewe

Altered expiratory flow dynamics at peak exercise in adult men with well-controlled type 1 diabetes.

Peer reviewe

Identifying Personality Characteristics and Indicators of Psychological Well-Being Associated With Attrition in the Motivation Makes the Move! Physical Activity Intervention: : Randomized Technology-Supported Trial

Peer reviewe

Density and function of actin-microdomains in healthy and NF1 deficient osteoclasts revealed by the combined use of atomic force and stimulated emission depletion microscopy

Actin and myosins (IIA, IIB, and X) generate mechanical forces in osteoclasts that drive functions such as migration and membrane trafficking. In neurofibromatosis, these processes are perturbed due to a mutation in neurofibromatosis type 1 (NF1) gene. This mutation leads to generation of hyperactive bone-resorbing osteoclasts that increases incidence of skeletal dysplasia e.g. early-onset osteoporosis in patients suffering from neurofibromatosis. To study the density and function of actin clusters in mutated cells we introduce a new approach for combined use of a stimulated emission depletion (STED) microscope with an atomic force microscope (AFM). We resolved actin-cores within actin-microdomains at four typical structures (podosome-belt, podosome raft, actin patches, and sealing zone) for osteoclasts cultured on bone as well as on glass. Densities of actin-cores in these structures were higher on bone than on glass, and the nearest neighbor distances were shortest in sealing zones, where also an accumulation of vesicular material was observed at their center. In NF1 deficient osteoclasts, the clustering was tighter and there was also more vesicular material accumulated inside the sealing zone. Using the STED-AFM system, we measured the condensation of the actin structures in real-time after a bone-coated cantilever was placed in contact with a differentiated osteoclast and found that the condensation of actin was initiated at 40 min, after sufficient local actin concentration was reached. A functional implication of the less dense clustering in NF1 deficient cells was that the adhesion of these cells was less specific for bone. The data and new methodologies presented here build a foundation for establishing novel actomyosin dependent mechanisms during osteoclast migration and resorption.</p

Density and function of actin-microdomains in healthy and NF1 deficient osteoclasts revealed by the combined use of atomic force and stimulated emission depletion microscopy

n/

Functional expression of NF1 tumor suppressor protein: association with keratin intermediate filaments during the early development of human epidermis

BACKGROUND: NF1 refers to type 1 neurofibromatosis syndrome, which has been linked with mutations of the large NF1 gene. NF1 tumor suppressor protein, neurofibromin, has been shown to regulate ras: the NF1 protein contains a GTPase activating protein (GAP) related domain which functions as p21rasGAP. Our studies have previously demonstrated that the NF1 protein forms a high affinity association with cytokeratin 14 during the formation of desmosomes and hemidesmosomes in cultured keratinocytes. METHODS: The expression of NF1 protein was studied in developing human epidermis using western transfer analysis, indirect immunofluorescence, confocal laser scanning microscopy, immunoelectron microscopy, and in situ hybridization. RESULTS: The expression of NF1 protein was noted to be highly elevated in the periderm at 8 weeks estimated gestational age (EGA) and in the basal cells at 8–14 weeks EGA. During this period, NF1 protein was associated with cytokeratin filaments terminating to desmosomes and hemidesmosomes. NF1 protein did not display colocalization with α-tubulin or actin of the cytoskeleton, or with adherens junction proteins. CONCLUSIONS: These results depict an early fetal period when the NF1 tumor suppressor is abundantly expressed in epidermis and associated with cytokeratin filaments. This period is characterized by the initiation of differentiation of the basal cells, maturation of the basement membrane zone as well as accentuated formation of selected cellular junctions. NF1 tumor suppressor may function in the regulation of epidermal histogenesis via controlling the organization of the keratin cytoskeleton during the assembly of desmosomes and hemidesmosomes

Altered cardiorespiratory response to exercise in overweight and obese women with polycystic ovary syndrome

In polycystic ovary syndrome (PCOS), cardiovascular risk is increased. Peak O2 uptake (V˙O2peak) predicts the cardiovascular risk. We were the first to examine the contribution of systemic O2 delivery and arteriovenous O2 difference to V˙O2peak in overweight and obese women with PCOS. Fifteen overweight or obese PCOS women and 15 age-, anthropometry-, and physical activity-matched control women performed a maximal incremental cycling exercise test. Alveolar gas exchange (volume turbine and mass spectrometry), arterial O2 saturation (pulse oximetry), and cardiac output (CO) (impedance cardiography) were monitored. Hb concentration was determined. Arterial O2 content and arteriovenous O2 difference (C(a-v)O2) (Fick equation) were calculated. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR). PCOS women had lower V˙O2peak than controls (40 ± 6 vs. 46 ± 5 mL/min/kg fat-free mass [FFM], P = 0.011). Arterial O2 content was similarly maintained in the groups throughout the exercise test (P > 0.05). Linear regression analysis revealed a pronounced response of CO to increasing V˙O2 in PCOS women during the exercise test: A ∆CO/∆V˙O2 slope was steeper in PCOS women than in controls (β = 5.84 vs. β = 5.21, P = 0.004). Eventually, the groups attained similar peak CO and peak CO scaled to FFM (P > 0.05). Instead, C(a-v)O2 at peak exercise was lower in PCOS women than in controls (13.2 ± 1.6 vs. 14.8 ± 2.4 mL O2/100 mL blood, P = 0.044). HOMA-IR was similar in the groups (P > 0.05). The altered cardiorespiratory responses to exercise in overweight and obese PCOS women indicate that PCOS per se is associated with alterations in peripheral adjustments to exercise rather than with limitations of systemic O2 delivery.Peer reviewe

Heart rate variability changes at 2400 m altitude predicts acute mountain sickness on further ascent at 3000-4300 m altitudes

Objective: If the body fails to acclimatize at high altitude, acute mountain sickness (AMS) may result. For the early detection of AMS, changes in cardiac autonomic function measured by heart rate variability (HRV) may be more sensitive than clinical symptoms alone. The purpose of this study was to ascertain if the changes in HRV during ascent are related to AMS. Methods: We followed Lake Louise Score (LLS), arterial oxygen saturation at rest (R-SpO(2)) and exercise (Ex-SpO(2)) and HRV parameters daily in 36 different healthy climbers ascending from 2400 m to 6300 m altitudes during five different expeditions. Results: After an ascent to 2400 m, root mean square successive differences, high-frequency power (HF2 min) of HRV were 17-51% and Ex-SpO(2) was 3% lower in those climbers who suffered from AMS at 3000 to 4300 m than in those only developing AMS later (>= 5000 m) or not at all (all p <0.01). At the altitude of 2400 m RMSSD2 minPeer reviewe

Respiratory plasticity in response to changes in oxygen supply and demand

Aerobic organisms maintain O2 homeostasis by responding to changes in O2 supply and demand in both short and long time domains. In this review, we introduce several specific examples of respiratory plasticity induced by chronic changes in O2 supply (environmental hypoxia or hyperoxia) and demand (exercise-induced and temperature-induced changes in aerobic metabolism). These studies reveal that plasticity occurs throughout the respiratory system, including modifications to the gas exchanger, respiratory pigments, respiratory muscles, and the neural control systems responsible for ventilating the gas exchanger. While some of these responses appear appropriate (e.g., increases in lung surface area, blood O2 capacity, and pulmonary ventilation in hypoxia), other responses are potentially harmful (e.g., increased muscle fatigability). Thus, it may be difficult to predict whole-animal performance based on the plasticity of a single system. Moreover, plastic responses may differ quantitatively and qualitatively at different developmental stages. Much of the current research in this field is focused on identifying the cellular and molecular mechanisms underlying respiratory plasticity. These studies suggest that a few key molecules, such as hypoxia inducible factor (HIF) and erythropoietin, may be involved in the expression of diverse forms of plasticity within and across species. Studying the various ways in which animals respond to respiratory challenges will enable a better understanding of the integrative response to chronic changes in O2 supply and deman