Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle: Differential effects on insulin-receptor substrates 1 and 2

Abstract

Level of physical activity is linked to improved glucose homeostasis. We determined whether exercise alters the expression and͞or activity of proteins involved in insulin-signal transduction in skeletal muscle. Wistar rats swam 6 h per day for 1 or 5 days. Epitrochlearis muscles were excised 16 h after the last exercise bout, and were incubated with or without insulin (120 nM). Insulin-stimulated glucose transport increased 30% and 50% after 1 and 5 days of exercise, respectively. Glycogen content increased 2-and 4-fold after 1 and 5 days of exercise, with no change in glycogen synthase expression. Protein expression of the glucose transporter GLUT4 and the insulin receptor increased 2-fold after 1 day, with no further change after 5 days of exercise. Insulinstimulated receptor tyrosine phosphorylation increased 2-fold after 5 days of exercise. Insulin-stimulated tyrosine phosphorylation of insulin-receptor substrate (IRS) 1 and associated phosphatidylinositol (PI) 3-kinase activity increased 2.5-and 3.5-fold after 1 and 5 days of exercise, despite reduced (50%) IRS-1 protein content after 5 days of exercise. After 1 day of exercise, IRS-2 protein expression increased 2.6-fold and basal and insulin-stimulated IRS-2 associated PI 3-kinase activity increased 2.8-fold and 9-fold, respectively. In contrast to IRS-1, IRS-2 expression and associated PI 3-kinase activity normalized to sedentary levels after 5 days of exercise. Insulin-stimulated Akt phosphorylation increased 5-fold after 5 days of exercise. In conclusion, increased insulin-stimulated glucose transport after exercise is not limited to increased GLUT4 expression. Exercise leads to increased expression and function of several proteins involved in insulin-signal transduction. Furthermore, the differential response of IRS-1 and IRS-2 to exercise suggests that these molecules have specialized, rather than redundant, roles in insulin signaling in skeletal muscle.

Effects of Endurance Exercise Training on Insulin Signaling in Human Skeletal Muscle

“…8). This reduction could not be attributed to changes in protein content of either IRS-1 or the p85 regulatory subunit of PI3-K and seems to be contradictory to the finding of improved PI3-K signaling after training in rodent muscle (13,14,40,41). However, the existing data in human skeletal muscle are not equivocal.…”

“…Furthermore, exercise training results in changes in expression and/or activity of proteins involved in glucose uptake/metabolism in both rodent (13,14) and human skeletal muscle (2,(15)(16)(17). Although only a few observations have been made in human muscle, insulin signaling to stimulate glucose uptake may be improved under some exercise training conditions.…”

Dynamic 31P–MRSI using spiral spectroscopic imaging can map mitochondrial capacity in muscles of the human calf during plantar flexion exercise at 7 T

“…Duchenne muscular dystrophy1 or mitochondrial myopathy2), systemic metabolic diseases (e.g. diabetes mellitus3, 4) and cardiovascular diseases (e.g. peripheral arterial disease (PAD)5, 6, 7).…”

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

“…Chronic exercise training is also associated with changes in signal transduction and gene expression. In rodents, acute (1 day) and short-term (5 days) exercise training are associated with an increase in insulin signal transduction and glucose uptake in skeletal muscle [15]. Likewise in young healthy humans, short-term (7 days) exercise increases insulinmediated whole-body glucose disposal, PI3K signalling [14,16] and GLUT4 protein content [17][18][19][20][21][22].…”