The purpose of this study was to determine the time course of GLUT4 protein accumulation following an exercise-carbohydrate supplementation regimen, and to evaluate the effect of this regimen on GLUT4 mRNA regulation. Rats were exercised by swimming and intubated with 1 mL of a 50% glucose solution immediately post-exercise. Exercise significantly reduced muscle glycogen by 50%. By 1.5 h of recovery, muscle glycogen was normalized, but continued to increase above the control level during the next 16 h. A faster and larger repletion of glycogen occurred in the fast-twitch red compared with the fast-twitch white muscle during the 16 h of recovery. GLUT4 protein concentration in fast-twitch red muscle was significantly increased above control by 1.5 h of recovery, and progressively increased throughout the recovery period. Fast-twitch white muscle demonstrated a similar trend, but the increase in GLUT4 protein did not reach significance until 5 h of recovery. Fast-twitch red muscle GLUT4 mRNA was increased by 53% above control immediately post-exercise, but returned to the control level by 1.5 h of recovery. GLUT4 mRNA associated with polysomes, however, increased significantly during this time and remained elevated for a minimum of 5 h. The results suggest that the increased GLUT4 protein expression following a regimen of exercise-carbohydrate supplementation occurs sufficiently fast to contribute to the resynthesis of muscle glycogen, and is controlled by both pre-translational and translational mechanisms.

The pattern of muscle glycogen synthesis following its depletion by exercise is biphasic. Initially, there is a rapid, insulin independent increase in the muscle glycogen stores. This is then followed by a slower insulin dependent rate of synthesis. Contributing to the rapid phase of glycogen synthesis is an increase in muscle cell membrane permeability to glucose, which serves to increase the intracellular concentration of glucose-6-phosphate (G6P) and activate glycogen synthase. Stimulation of glucose transport by muscle contraction as well as insulin is largely mediated by translocation of the glucose transporter isoform GLUT4 from intracellular sites to the plasma membrane. Thus, the increase in membrane permeability to glucose following exercise most likely reflects an increase in GLUT4 protein associated with the plasma membrane. This insulin-like effect on muscle glucose transport induced by muscle contraction, however, reverses rapidly after exercise is stopped. As this direct effect on transport is lost, it is replaced by a marked increase in the sensitivity of muscle glucose transport and glycogen synthesis to insulin. Thus, the second phase of glycogen synthesis appears to be related to an increased muscle insulin sensitivity. Although the cellular modifications responsible for the increase in insulin sensitivity are unknown, it apparently helps maintain an increased number of GLUT4 transporters associated with the plasma membrane once the contraction-stimulated effect on translocation has reversed. It is also possible that an increase in GLUT4 protein expression plays a role during the insulin dependent phase.

Exercise training prevented hypertension-enhanced cardiac Fas-dependent and mitochondria-dependent apoptotic pathways and enhanced cardiac pro-survival pathway in rat models. Our findings demonstrate new therapeutic effects of exercise training on hypertensive hearts for preventing apoptosis and enhancing survival.

No abstract

We investigated the influence of resistance exercise (RE) with different intensities on HbA1c, insulin and blood glucose levels in patients with type 2 diabetes (T2D). Diabetes trials that compared RE group with a control were included in meta-analysis. Exercise intensities were categorized into low-to-moderate-intensity and high-intensity subgroups. Intensity effect on glycemic control was determined by meta-regression analysis, and risk-of-bias was assessed using Cochrane Collaboration tool. 24 trials met the inclusion criteria, comprised of 962 patients of exercise (n = 491) and control (n = 471). Meta-regression analysis showed decreased HbA1c (p = 0.006) and insulin (p = 0.015) after RE was correlated with intensity. Subgroup analysis revealed decreased HbA1c was greater with high intensity (−0.61; 95% CI −0.90, −0.33) than low-to-moderate intensity (−0.23; 95% CI −0.41, −0.05). Insulin levels were significantly decreased only with high intensity (−4.60; 95% CI −7.53, −1.67), not with low-to-moderate intensity (0.07; 95% CI −3.28, 3.42). Notably, values between the subgroups were statistically significant for both HbA1c (p = 0.03) and insulin (p = 0.04), indicative of profound benefits of high-intensity RE. Pooled outcomes of 15 trials showed only a decreased trend in blood glucose with RE (p = 0.09), and this tendency was not associated with intensity. Our meta-analysis provides additional evidence that high-intensity RE has greater beneficial effects than low-to-moderate-intensity in attenuation of HbA1c and insulin in T2D patients.

Lai Y-C, Stuenaes JT, Kuo C-H, Jensen J. Glycogen content and contraction regulate glycogen synthase phosphorylation and affinity for UDP-glucose in rat skeletal muscles.

No abstract

Invasion of distant tissues by tumor cells is the primary cause of therapeutic failure in the treatment of malignant lung cancer cells. Receptor activator of nuclear factor-κB ligand (RANKL) and its receptor, RANK, play a key role in osteoclastogenesis and tumor metastasis. Intercellular adhesion molecule-1 (ICAM-1, also called CD54), a member of the immunoglobulin supergene family, is an inducible surface glycoprotein that mediates adhesion-dependent cell-to-cell interactions. The effects of RANKL on cell migration and ICAM-1 expression in human lung cancer cells are largely unknown. We found that RANKL directed the migration and increased ICAM-1 expression in human lung cancer (A549) cells. Pretreatment of A549 cells with the MAPK kinase (MEK) inhibitor PD98059 or U0126 inhibited RANKL-mediated migration and ICAM-1 expression. Stimulation of cells with RANKL increased the phosphorylation of MEK and extracellular signal-regulating kinase (ERK). In addition, an NF-κB inhibitor (PDTC) and IκB protease inhibitor (TPCK) also inhibited RANKL-mediated cell migration and ICAM-1 up-regulation. Taken together, these results suggest that the RANKL and RANK interaction acts through MEK/ERK, which in turn activates NF-κB, resulting in the activation of ICAM-1 and contributing to the migration of human lung cancer cells.