Exercise modulates the insulin-induced translocation of glucose transporters in rat skeletal muscle

AbstractInsulin and acute exercise (45 min of treadmill run) increased glucose uptake into perfused rat hindlimbs 5-fold and 3.2-fold, respectively. Following exercise, insulin treatment resulted in a further increase in glucose uptake. The subcellular distribution of the muscle glucose transporters GLUT-1 and GLUT-4 was determined in plasma membranes and intracellular membranes. Neither exercise nor exercise→ insulin treatment altered the distribution of GLUT-1 transporters in these medmbrane fractions. In contrast, exercise, insulin and exercise→ insulin treatment caused comparable increases in GLUT-4 transporters in the plasma membrane. The results suggest that exercise might limit insulin-induced GLUT-4 recruitment and that following exercise, insulin may alter the intrinsic activity of plasma membrane glucose transporters

Environmental contaminants as etiologic factors for diabetes.

For both type 1 and type 2 diabetes mellitus, the rates have been increasing in the United States and elsewhere; rates vary widely by country, and genetic factors account for less than half of new cases. These observations suggest environmental factors cause both type 1 and type 2 diabetes. Occupational exposures have been associated with increased risk of diabetes. In addition, recent data suggest that toxic substances in the environment, other than infectious agents or exposures that stimulate an immune response, are associated with the occurrence of these diseases. We reviewed the epidemiologic data that addressed whether environmental contaminants might cause type 1 or type 2 diabetes. For type 1 diabetes, higher intake of nitrates, nitrites, and N-nitroso compounds, as well as higher serum levels of polychlorinated biphenyls have been associated with increased risk. Overall, however, the data were limited or inconsistent. With respect to type 2 diabetes, data on arsenic and 2,3,7,8-tetrachlorodibenzo-p-dioxin relative to risk were suggestive of a direct association but were inconclusive. The occupational data suggested that more data on exposure to N-nitroso compounds, arsenic, dioxins, talc, and straight oil machining fluids in relation to diabetes would be useful. Although environmental factors other than contaminants may account for the majority of type 1 and type 2 diabetes, the etiologic role of several contaminants and occupational exposures deserves further study

Regulation of Skeletal Muscle Glucose Transport and Glucose Metabolism by Exercise Training

Aerobic exercise training and resistance exercise training are both well-known for their ability to improve human health; especially in individuals with type 2 diabetes. However, there are critical differences between these two main forms of exercise training and the adaptations that they induce in the body that may account for their beneficial effects. This article reviews the literature and highlights key gaps in our current understanding of the effects of aerobic and resistance exercise training on the regulation of systemic glucose homeostasis, skeletal muscle glucose transport and skeletal muscle glucose metabolism

Quantitative immunofluorescence microscopy of subcellular GLUT4 distribution in human skeletal muscle: effects of endurance and sprint interval training.

Increases in insulin-mediated glucose uptake following endurance training (ET) and sprint interval training (SIT) have in part been attributed to concomitant increases in glucose transporter 4 (GLUT4) protein content in skeletal muscle. This study used an immunofluorescence microscopy method to investigate changes in subcellular GLUT4 distribution and content following ET and SIT. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of 16 sedentary males in the overnight fasted state before and after 6 weeks of ET and SIT. An antibody was fully validated and used to show large (> 1 μm) and smaller (<1 μm) GLUT4-containing clusters. The large clusters likely represent trans-Golgi network stores and the smaller clusters endosomal stores and GLUT4 storage vesicles (GSVs). Density of GLUT4 clusters was higher at the fibre periphery especially in perinuclear regions. A less dense punctate distribution was seen in the rest of the muscle fibre. Total GLUT4 fluorescence intensity increased in type I and type II fibres following both ET and SIT. Large GLUT4 clusters increased in number and size in both type I and type II fibres, while the smaller clusters increased in size. The greatest increases in GLUT4 fluorescence intensity occurred within the 1 μm layer immediately adjacent to the PM. The increase in peripheral localisation and protein content of GLUT4 following ET and SIT is likely to contribute to the improvements in glucose homeostasis observed after both training modes

Role of PKCΖ translocation in the development of type 2 diabetes in rats following continuous glucose infusion

Aim We investigated the molecular mechanisms of hyperglycaemia-induced insulin resistance and type 2 diabetes in rats receiving a continuous glucose infusion (GI). Methods Female Wistar rats were infused with either 2.8 mol/L glucose or saline (2 mL/h) for durations varying from 0 to 15 days. Blood samples were analysed daily to determine glucose and insulin dynamics. Subsets of animals were sacrificed and solues muscles were extracted for determination of protein expression, subcellular location, and activities of insulin-signalling proteins. Results Rats accommodated this systemic glucose oversupply and developed insulin resistance on day 5 (normoglycaemia/hyperinsulinaemia) and type 2 diabetes on day 15 (hyperglycaemia/normoinsulinaemia). The effect of GI on protein kinase CΖ (PKCΖ) activity was independent of changes in phosphatidylinositol 3-kinase activity, and occurred in parallel with an increase in PDK1 activity. Activated PKCΖ was mainly located in the cytosol after 5 days of GI that was coincident with the translocation of GLUT4 to the plasma membrane, and normoglycaemia. After 15 days of GI, PKCΖ translocated from the cytosol to the plasma membrane with a concomitant decrease in PDK1 activity. This caused an increase in the association between PKCΖ and PKB and a decrease in PDK1–PKB reactions at the plasma membrane, leading to reduced PKB activity. The activity of PKCΖ per se was also compromised. The PKCΖ and PKB activity reduction and the blunted insulin-stimulated GLUT4 translocation eventually led to hyperglycaemia and diabetes. Conclusion Translocation of PKCΖ may play a central role in the development of type 2 diabetes. Copyright © 2009 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64921/1/1056_ftp.pd

Physical Activity May Facilitate Diabetes Prevention in Adolescents

OBJECTIVE—The aim of this study was to examine the association of physical activity with glucose tolerance and resting energy expenditure (REE) among adolescents

Extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin adjustments in individuals with type 1 diabetes

To detail the extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin dose adjustments in individuals with type 1 diabetes (T1D) using multiple daily injections of insulins aspart (IAsp) and degludec (IDeg)

Electrical Pulse Stimulation of Cultured Human Skeletal Muscle Cells as an In Vitro Model of Exercise

Background and Aims Physical exercise leads to substantial adaptive responses in skeletal muscles and plays a central role in a healthy life style. Since exercise induces major systemic responses, underlying cellular mechanisms are difficult to study in vivo. It was therefore desirable to develop an in vitro model that would resemble training in cultured human myotubes. Methods Electrical pulse stimulation (EPS) was applied to adherent human myotubes. Cellular contents of ATP, phosphocreatine (PCr) and lactate were determined. Glucose and oleic acid metabolism were studied using radio-labeled substrates, and gene expression was analyzed using real-time RT-PCR. Mitochondrial content and function were measured by live imaging and determination of citrate synthase activity, respectively. Protein expression was assessed by electrophoresis and immunoblotting. Results High-frequency, acute EPS increased deoxyglucose uptake and lactate production, while cell contents of both ATP and PCr decreased. Chronic, low-frequency EPS increased oxidative capacity of cultured myotubes by increasing glucose metabolism (uptake and oxidation) and complete fatty acid oxidation. mRNA expression level of pyruvate dehydrogenase complex 4 (PDK4) was significantly increased in EPS-treated cells, while mRNA expressions of interleukin 6 (IL-6), cytochrome C and carnitin palmitoyl transferase b (CPT1b) also tended to increase. Intensity of MitoTracker®Red FM was doubled after 48 h of chronic, low-frequency EPS. Protein expression of a slow fiber type marker (MHCI) was increased in EPS-treated cells. Conclusions Our results imply that in vitro EPS (acute, high-frequent as well as chronic, low-frequent) of human myotubes may be used to study effects of exercise.This work was funded by the University of Oslo, Oslo University College, the Norwegian Diabetes Foundation, the Freia Chocolade Fabriks Medical Foundation and the Anders Jahre’s Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Music and the brain: disorders of musical listening

The study of the brain bases for normal musical listening has advanced greatly in the last 30 years. The evidence from basic and clinical neuroscience suggests that listening to music involves many cognitive components with distinct brain substrates. Using patient cases reported in the literature, we develop an approach for understanding disordered musical listening that is based on the systematic assessment of the perceptual and cognitive analysis of music and its emotional effect. This approach can be applied both to acquired and congenital deficits of musical listening, and to aberrant listening in patients with musical hallucinations. Both the bases for normal musical listening and the clinical assessment of disorders now have a solid grounding in systems neuroscience