Glucose: not always the bad guy.

Commentary on: Wei J, Shimazu J, Makinistoglu MP, Maurizi A, Kajimura D, Zong H et al. Glucose uptake and Runx2 synergize to orchestrate osteoblast differentiation and bone formation. Cell 2015; 161(7): 1576–1591

The effects of knee injury on skeletal muscle function, Na+, K+-ATPase content, and isoform abundance.

While training upregulates skeletal muscle Na+, K+‐ATPase (NKA), the effects of knee injury and associated disuse on muscle NKA remain unknown. This was therefore investigated in six healthy young adults with a torn anterior cruciate ligament, (KI; four females, two males; age 25.0 ± 4.9 years; injury duration 15 ± 17 weeks; mean ± SD) and seven age‐ and BMI‐matched asymptomatic controls (CON; five females, two males). Each participant underwent a vastus lateralis muscle biopsy, on both legs in KI and one leg in CON. Muscle was analyzed for muscle fiber type and cross‐sectional area (CSA), NKA content ([3H]ouabain binding), and α1–3 and β1–2 isoform abundance. Participants also completed physical activity and knee function questionnaires (KI only); and underwent quadriceps peak isometric strength, thigh CSA and postural sway assessments in both injured and noninjured legs. NKA content was 20.1% lower in the knee‐injured leg than the noninjured leg and 22.5% lower than CON. NKA α2 abundance was 63.0% lower in the knee‐injured leg than the noninjured leg, with no differences in other NKA isoforms. Isometric strength and thigh CSA were 21.7% and 7.1% lower in the injured leg than the noninjured leg, respectively. In KI, postural sway did not differ between legs, but for two‐legged standing was 43% higher than CON. Hence, muscle NKA content and α2 abundance were reduced in severe knee injury, which may contribute to impaired muscle function. Restoration of muscle NKA may be important in rehabilitation of muscle function after knee and other lower limb injury

The evolution of technology and physical inactivity: The good, the bad, and the way forward

Since the beginning of time people explored and developed new technologies to make their activities of daily living less labour intense, more efficient and, consequently, more sedentary. In addition, technological advances in medicine throughout history have led to a substantial increase in life expectancy. However, the combination of increased sedentary behaviour and increased life-expectancy resulted in a sharp increase in overweight and obesity related chronic conditions and illness. Although people may live longer, they are doing so with poorer physical function and a reduced quality of life. In this review we explore how technological advances have influenced people's sedentary behaviour and, through the lens of the affective-reflective theory (ART), we propose a means by which technology could be repurposed to encourage greater engagement in physical activity

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

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

Clinical utility of exercise training in heart failure with reduced and preserved ejection fraction

Reduced exercise tolerance is an independent predictor of hospital readmission and mortality in patients with heart failure (HF). Exercise training for HF patients is well established as an adjunct therapy, and there is sufficient evidence to support the favorable role of exercise training programs for HF patients over and above the optimal medical therapy. Some of the documented benefits include improved functional capacity, quality of life (QoL), fatigue, and dyspnea. Major trials to assess exercise training in HF have, however, focused on heart failure with reduced ejection fraction (HFREF). At least half of the patients presenting with HF have heart failure with preserved ejection fraction (HFPEF) and experience similar symptoms of exercise intolerance, dyspnea, and early fatigue, and similar mortality risk and rehospitalization rates. The role of exercise training in the management of HFPEF remains less clear. This article provides a brief overview of pathophysiology of reduced exercise tolerance in HFREF and heart failure with preserved ejection fraction (HFPEF), and summarizes the evidence and mechanisms by which exercise training can improve symptoms and HF. Clinical and practical aspects of exercise training prescription are also discussed

Psychological responses to acute aerobic, resistance, or combined exercise in healthy and overweight individuals: A systematic review

Introduction: Psychological distress and depression are risk factors for cardiovascular disease (CVD). As such, a reduction in psychological distress and increase in positive well-being may be important to reduce the risk for future development of CVD. Exercise training may be a good strategy to prevent and assist in the management of psychological disorders. The psychological effects of the initial exercise sessions may be important to increase exercise adherence. The aims of this systematic review were (a) to examine whether acute aerobic, resistance, or a combination of the 2 exercises improves psychological well-being and reduces psychological distress in individuals with healthy weight and those who are overweight/obese but free from psychological disorders, and (b) if so, to examine which form of exercise might yield superior results. Methods: The online database PubMed was searched for articles using the PICO (patient, intervention, comparison, and outcome) framework for finding scientific journals based on key terms. Results: Forty-two exercise studies met the inclusion criteria. A total of 2187 participants were included (age: 18-64 years, body mass index [BMI]: 21-39 kg/m 2 ). Only 6 studies included participants with a BMI in the overweight/obese classification. Thirty-seven studies included aerobic exercise, 2 included resistance exercise, 1 used a combination of aerobic and resistance, and 2 compared the effects of acute aerobic exercise versus the effects of acute resistance exercise. The main findings of the review were that acute aerobic exercise improves positive well-being and have the potential to reduce psychological distress and could help reduce the risks of future CVD. However, due to the limited number of studies, it is still unclear which form of exercise yields superior psychological benefits. Conclusions: Obese, overweight, and healthy weight individuals can exhibit psychological benefits from exercise in a single acute exercise session, and these positive benefits of exercise should be used by health professionals as a tool to increase long-term participation in exercise in these populations

Osteocalcin and vascular function: is there a cross-talk?

Background: The bone-derived protein osteocalcin (OC), in its undercarboxylated (ucOC) form, has a beneficial effect on energy metabolism and may be a future therapeutic target for metabolic diseases. Increasing evidence suggests a link between ucOC and cardiovascular disease (CVD) development; however, the exact relationship is conflicting and unclear. Scope of review: The aim of this review was to summarise the current research examining the interaction between OC and vascular dysfunction, the initiating stage in the development of atherosclerosis and CVD. Major conclusions: In humans, the association between OC and vascular function is inconsistent. Several studies report that total OC (tOC) is associated with adverse function or beneficial function, whereas others report that tOC and ucOC has no effect on vascular function. The conflicting data are likely due to several methodological inconsistencies, in particular the lack of studies reporting circulating ucOC levels. In animal models, the direct administration of ucOC to isolated blood vessels ex vivo produced minimal changes in endothelial function, but importantly, no adverse responses. Finally, in human endothelial and vascular smooth muscle cells, ucOC treatment did not influence classical markers of cellular function, including endothelin-1, vascular adhesion molecule-1 and monocyte chemoattractant protein-1 after exposure to high glucose and inflammatory conditions. The lack of adverse effects in ex vivo and in vitro studies suggests that ucOC may be targeted as a future therapeutic for metabolic diseases, without the risk of detrimental effects in the vasculature. However, further studies are needed to confirm these findings and to investigate whether there is a direct beneficial influence of ucOC

The Effect of an Atherogenic Diet and Acute Hyperglycaemia on Endothelial Function in Rabbits Is Artery Specific

Hyperglycaemia has a toxic effect on blood vessels and promotes coronary artery disease. It is unclear whether the dysfunction caused by hyperglycaemia is blood vessel specific and whether the dysfunction is exacerbated following an atherogenic diet. Abdominal aorta, iliac, and mesenteric arteries were dissected from New Zealand White rabbits following either a 4-week normal or atherogenic diet (n = 6-12 per group). The arteries were incubated ex vivo in control or high glucose solution (20 mM or 40 mM) for 2 h. Isometric tension myography was used to determine endothelial-dependent vasodilation. The atherogenic diet reduced relaxation as measured by area under the curve (AUC) by 25% (p < 0.05), 17% (p = 0.06) and 40% (p = 0.07) in the aorta, iliac, and mesenteric arteries, respectively. In the aorta from the atherogenic diet fed rabbits, the 20 mM glucose altered EC50 (p < 0.05). Incubation of the iliac artery from atherogenic diet fed rabbits in 40 mM glucose altered EC50 (p < 0.05). No dysfunction occurred in the mesentery with high glucose incubation following either the normal or atherogenic diet. High glucose induced endothelial dysfunction appears to be blood vessel specific and the aorta may be the optimal artery to study potential therapeutic treatments of hyperglycaemia induced endothelial dysfunction

Roles of bone-derived hormones in type 2 diabetes and cardiovascular pathophysiology

Background: Emerging evidence demonstrates that bone is an endocrine organ capable of influencing multiple physiological and pathological processes through the secretion of hormones. Recent research suggests complex crosstalk between the bone and other metabolic and cardiovascular tissues. It was uncovered that three of these bone-derived hormones—osteocalcin, lipocalin 2, and sclerostin—are involved in the endocrine regulations of cardiometabolic health and play vital roles in the pathophysiological process of developing cardiometabolic syndromes such as type 2 diabetes and cardiovascular disease. Chronic low-grade inflammation is one of the hallmarks of cardiometabolic diseases and a major contributor to disease progression. Novel evidence also implicates important roles of bone-derived hormones in the regulation of chronic inflammation. Scope of review: In this review, we provide a detailed overview of the physiological and pathological roles of osteocalcin, lipocalin 2, and sclerostin in cardiometabolic health regulation and disease development, with a focus on the modulation of chronic inflammation. Major conclusions: Evidence supports that osteocalcin has a protective role in cardiometabolic health, and an increase of lipocalin 2 contributes to the development of cardiometabolic diseases partly via pro-inflammatory effects. The roles of sclerostin appear to be complicated: It exerts pro-adiposity and pro-insulin resistance effects in type 2 diabetes and has an anti-calcification effect during cardiovascular disease. A better understanding of the actions of these bone-derived hormones in the pathophysiology of cardiometabolic diseases will provide crucial insights to help further research develop new therapeutic strategies to treat these diseases