Physical activity in normal and impaired glucose tolerance and Type 2 diabetes mellitus Effects of walking and Nordic walking on health-related quality of life, cardiovascular risk factors and mitochondrial gene expression in overweight individuals

Background and aim: Type 2 diabetes mellitus (T2DM) is a disease associated with the risk of severe cardiovascular complications. Genetic predisposition, a sedentary lifestyle and overweight may increase the risk of developing T2DM. The aim was to study the effects of physical activity on risk factors of cardiovascular disease, health-related quality of life, and on the gene expression of enzymes involved in glucose and lipid metabolism, in overweight people with T2DM, impaired or normal glucose tolerance. Methods: Two different exercise intervention studies were conducted, both for a fourmonth period. Study 1, presented in paper I, included 52 T2DM patients, 26 controls, 26 in an intervention group. The intervention was to increase physical activity by brisk walking, 45 minutes three times per week. At baseline and after four months we assessed systolic (SBP) and diastolic (DBP) blood pressure, body mass index (BMI), glucose and lipid metabolic parameters, self-reported physical activity and physical fitness. Study 2 (papers II, III and IV) included 212 overweight individuals. The intervention was a weekly physical activity increase by 5 hours of walking with walking poles (Nordic walking). The participants were classified by an oral glucose tolerance test (OGTT) with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM), and randomized into a control group (n=125), or an exercise intervention group (n=87). Health-related quality of life (HRQoL) was recorded by questionnaire (paper II), and anthropometric and clinical data (papers II & III) were assessed at the time of inclusion and after four months. From 79 NGT and 33 T2DM male exercise participants a 20–100 mg biopsy was taken from the quadriceps muscle of the thigh, for the assessment of messenger RNA (mRNA) expression of mitochondrial genes, coding for enzymes involved in glucose and fatty acid metabolism (paper IV). Results: In study 1 there were no significant improvements of anthropometric parameters, physical fitness, blood pressure, glucose or lipid metabolism. The 17 patients in the intervention group who attained ≥80% of the intended increment of physical activity significantly improved SBP, DBP, BMI and total plasma cholesterol, compared with the control group. In study 2 (papers II & III) quality of sleep, body weight, BMI and waist circumference were improved for NGT exercise participants, and in the IGT exercise group exercise capacity improved. Among the exercise participants ≥80% compliant with the scheduled time of Nordic walking, exercise capacity improved significantly in all three (NGT, IGT and T2DM) exercise groups. Blood pressure, glycaemic control and blood lipids were unaffected. Baseline mRNA expression of 3 mitochondrial genes was increased in the T2DM group (paper IV). In the NGT group the expression of the enzyme PDK4 was increased after the exercise period, but not in the T2DM group. Conclusions: The exercise participants ≥80% compliant with the exercise goals in paper I improved SBP, DBP and BMI. The exercise goal of Nordic walking, 5 hours per week, led to improved quality of sleep, body weight, BMI and waist circumference in the NGT group, and exercise capacity improved in the IGT group. The elevated baseline PDK4 expression and the unaltered post-exercise expression in the T2DM cohort may reflect an impaired utilization of glucose and lipid fuels inherent in T2DM, and a dysfunction of the appropriate adaptive responses to exercise in skeletal muscle associated with insulin resistance

Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle

SummaryDNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene expression. Whole genome methylation was decreased in skeletal muscle biopsies obtained from healthy sedentary men and women after acute exercise. Exercise induced a dose-dependent expression of PGC-1α, PDK4, and PPAR-δ, together with a marked hypomethylation on each respective promoter. Similarly, promoter methylation of PGC-1α, PDK4, and PPAR-δ was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle and suggest that DNA hypomethylation is an early event in contraction-induced gene activation

Afternoon exercise is more efficacious than morning exercise at improving blood glucose levels in individuals with type 2 diabetes : a randomised crossover trial

Data availability The data analysed during the current study are available from the corresponding author on reasonable request. Funding The authors are supported by grants from Novo Nordisk Foundation (NNF14OC0011493 and NNF14OC0009941), Swedish Diabetes Foundation (DIA2015-052), Wenner-Gren Foundation, Swedish Research Council (2015-00165), Strategic Research Program in Diabetes at Karolinska Institutet (2009-1068), Stockholm County Council (SLL20150517 and SLL20170159) and Swedish Heart Lung Foundation (20150423).Peer reviewedPublisher PD

Photoassociation spectroscopy of cold calcium atoms

Photoassociation spectroscopy experiments on 40Ca atoms close to the dissociation limit 4s4s 1S0 - 4s4p 1P1 are presented. The vibronic spectrum was measured for detunings of the photoassociation laser ranging from 0.6 GHz to 68 GHz with respect to the atomic resonance. In contrast to previous measurements the rotational splitting of the vibrational lines was fully resolved. Full quantum mechanical numerical simulations of the photoassociation spectrum were performed which allowed us to put constraints on the possible range of the calcium scattering length to between 50 a_0 and 300 a_0

Human Galectins Induce Conversion of Dermal Fibroblasts into Myofibroblasts and Production of Extracellular Matrix: Potential Application in Tissue Engineering and Wound Repair

Members of the galectin family of endogenous lectins are potent adhesion/growth-regulatory effectors. Their multi-functionality opens possibilities for their use in bioapplications. We studied whether human galectins induce the conversion of human dermal fibroblasts into myofibroblasts (MFBs) and the production of a bioactive extracellular matrix scaffold is suitable for cell culture. Testing a panel of galectins of all three subgroups, including natural and engineered variants, we detected activity for the proto-type galectin-1 and galectin-7, the chimera-type galectin-3 and the tandem-repeat-type galectin-4. The activity of galectin-1 required the integrity of the carbohydrate recognition domain. It was independent of the presence of TGF-beta 1, but it yielded an additive effect. The resulting MFBs, relevant, for example, for tumor progression, generated a matrix scaffold rich in fibronectin and galectin-1 that supported keratinocyte culture without feeder cells. Of note, keratinocytes cultured on this substratum presented a stem-like cell phenotype with small size and keratin-19 expression. In vivo in rats, galectin-1 had a positive effect on skin wound closure 21 days after surgery. In conclusion, we describe the differential potential of certain human galectins to induce the conversion of dermal fibroblasts into MFBs and the generation of a bioactive cell culture substratum. Copyright (C) 2011 S. Karger AG, Base

4-Methylumbelliferone improves the thermogenic capacity of brown adipose tissue.

Therapeutic increase of brown adipose tissue (BAT) thermogenesis is of great interest as BAT activation counteracts obesity and insulin resistance. Hyaluronan (HA) is a glycosaminoglycan, found in the extracellular matrix, which is synthesized by HA synthases (Has1/Has2/Has3) from sugar precursors and accumulates in diabetic conditions. Its synthesis can be inhibited by the small molecule 4-methylumbelliferone (4-MU). Here, we show that the inhibition of HA-synthesis by 4-MU or genetic deletion of Has2/Has3 improves BAT`s thermogenic capacity, reduces body weight gain, and improves glucose homeostasis independently from adrenergic stimulation in mice on diabetogenic diet, as shown by a magnetic resonance T2 mapping approach. Inhibition of HA synthesis increases glycolysis, BAT respiration and uncoupling protein 1 expression. In addition, we show that 4-MU increases BAT capacity without inducing chronic stimulation and propose that 4-MU, a clinically approved prescription-free drug, could be repurposed to treat obesity and diabetes

Polymerase chain reaction amplifying mycobacterial DNA from aspirates obtained by endoscopic ultrasound allows accurate diagnosis of mycobacterial disease in HIV-positive patients with abdominal lymphadenopathy

Abdominal lymphadopathy in Human Immunodeficiency Virus (HIV) infection remains a diagnostic challenge. We performed a prospective cohort study recruiting thirty-one symptomatic HIV+ patients with abdominal lymphadenopathy assessing diagnostic yield of endoscopic ultrasound (EUS) fine needle aspiration (FNA). Mean age was 38 years, 52% were female, mean CD4 count and viral load were 124 cells/pl, and 4 log respectively. EUS confirmed additional mediastinal nodes in 26 %. Porta- hepatis was the most common abdominal site. EUS FNA was subjected to cytology, culture and polymerase chain reaction (PCR) analysis. Mycobacterial infections were confirmed in 67.7% and 31% had reactive lymphadenopathy. Cytology and culture had low sensitivity whereas PCR identified 90% of mycobacterial infections. Combining appearance of EUS FNA and cytology a diagnostic algorithm was developed to indicate when analysis with PCR would be useful. PCR performed on an EUS guided aspirate was highly accurate in confirming mycobacterial disease and determining genotypic drug resistance.South African Gastroenterological Society (SAGES)/ Astra Zeneca Fellowship in Gastroenterology awarded to Schalk van der Merwehttp://www.journals.elsevier.com/ultrasound-in-medicine-and-biology/hb201