Exercise training increases insulin-stimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes

Abstract

Aims/hypothesis Exercise enhances insulin-stimulated glucose transport in skeletal muscle through changes in signal transduction and gene expression. The aim of this study was to assess the impact of acute and short-term exercise training on whole-body insulin-mediated glucose disposal and signal transduction along the canonical insulin signalling cascade. Methods A euglycaemic-hyperinsulinaemic clamp, with vastus lateralis skeletal muscle biopsies, was performed at baseline and 16 h after an acute bout of exercise and shortterm exercise training (7 days) in obese non-diabetic (n=7) and obese type 2 diabetic (n=8) subjects. Results Insulin-mediated glucose disposal was unchanged following acute exercise in both groups. Short-term exercise training increased insulin-mediated glucose disposal in obese type 2 diabetic (p<0.05), but not in obese non-diabetic subjects. Insulin activation of (1) IRS1, (2) IRS2, (3) phosphotyrosine-associated phosphatidylinositol-3 kinase activity and (4) the substrate of phosphorylated Akt, AS160, a functional Rab GTPase activating protein important for GLUT4 (now known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) translocation, was unchanged after acute or chronic exercise in either group. GLUT4 protein content was increased in obese type 2 diabetic subjects (p<0.05), but not in obese non-diabetic subjects following chronic exercise. Conclusions/interpretation Exercise training increased whole-body insulin-mediated glucose disposal in obese type 2 diabetic patients. These changes were independent of functional alterations in the insulin-signalling cascade and related to increased GLUT4 protein content.

Physical Activity and Insulin Sensitivity

“…We and others (21,22) have shown that aerobic exercise has a dose-and intensity-related effect to increase insulin signaling and glucose transporter content in skeletal muscle. Exercise training increases insulin-stimulated glucose disposal and GLUT-4 (SLC2A4) protein content in obese patients with type 2 diabetes (22). High levels of sedentary time produce the reverse effect.…”

Early-onset type 2 diabetes in obese white subjects is characterised by a marked defect in beta cell insulin secretion, severe insulin resistance and a lack of response to aerobic exercise training

“…The landmark diabetes prevention studies have proven the efficacy of exercise intervention in preventing progression from IGT to diabetes [9,11,12]. We have recently shown that just 7 days of exercise training led to increased glucose disposal and muscle GLUT4 protein content in middle-aged, obese subjects with type 2 diabetes (mean age 45 years, BMI 36 kg/m 2 ) [15]. Since early-onset type 2 diabetes is characterised by obesity and severe insulin resistance, we chose to investigate the effect of exercise intervention in younger subjects with type 2 diabetes.…”

“…Smaller studies have shown that exercise improves insulin sensitivity and glucose metabolism [13,14]. We have recently shown that short-term exercise training increased insulin sensitivity by more than 50% in obese middle-aged patients (mean age 45 years) with type 2 diabetes [15]. In these patients the main biochemical change was an increase in glucose transporter 4 (GLUT4) protein content in skeletal muscle.…”

Efficacy of telephone support as a tool for promoting daily physical activity in type 2 diabetic patients

“…Training can enhance the responsiveness of skeletal muscles to insulin with increased expression and/or activity of proteins involved in glucose metabolism and insulin signaling. Moderate training may increase glycogen synthase activity and GLUT4 protein expression but not insulin signaling [29]. Fat oxidation is also a key aspect of improved insulin action, and training increases lipid storage in muscles and fat oxidation capacity [30].…”