Fatty acids inhibit insulin-mediated glucose transport associated with actin remodeling in rat L6 muscle cells

Abstract

In skeletal muscle cells, insulin stimulates cytoskeleton actin remodeling to facilitate the translocation of glucose transporter GLUT4 to plasma membrane. Defect of insulin-induced GLUT4 translocation and actin remodeling may cause insulin resistance. Free fatty acids cause insulin resistance in skeletal muscle. The aim of this study was to investigate the effects of fatty acids on glucose transport and actin remodeling. Differentiated L6 muscle cells expressing c-myc epitope-tagged GLUT4 were treated with palmitic acid, linoleic acid and oleic acid. Surface GLUT4 and 2-deoxyglucose uptake were measured in parallel with the morphological imaging of actin remodeling and GLUT4 immunoreactivity with fluorescence, confocal and transmission electron microscopy. Differentiated L6 cells showed concentration responses of insulin-induced actin remodeling and glucose uptake. The ultrastructure of insulin-induced actin remodeling was cell projections clustered with actin and GLUT4. Acute and chronic treatment with the 3 fatty acids had no effect on insulin-induced actin remodeling and GLUT4 immunoreactivity. However, insulin-mediated glucose uptake significantly decreased by palmitic acid (25, 50, 75, 100 μmol/L), oleic acid (180, 300 μmol/L) and linoleic acid (120, 180, 300 μmol/L). Oleic acid (120, 300 μmol/L) and linoleic acid (300 μmol/L), but not palmitic acid, significantly decreased insulin-mediated GLUT4 translocation. These data suggest that fatty acids inhibit insulin-induced glucose transport associated with actin remodeling in L6 muscle cells.

Calcitonin Participant in the Development of Insulin Resistance

“…Free fatty acids are considered as a new marker of IR [17]. The investigations of the last years were shown that fatty acids inhibit insulin-stimulated glucose transport in muscle cells [18]. It is also established, that chronic increasing of free fatty acids in serum leads to IR development [15] and that fatty acids induce IR of man skeletal muscles due to the defects of insulin-dependent glucose transportation [18].…”

“…The investigations of the last years were shown that fatty acids inhibit insulin-stimulated glucose transport in muscle cells [18]. It is also established, that chronic increasing of free fatty acids in serum leads to IR development [15] and that fatty acids induce IR of man skeletal muscles due to the defects of insulin-dependent glucose transportation [18]. Enhanced free fatty acids level reveals the direct metotoxical effect on the secretory function of pancreas β-cells and decreases insulin-dependent glucose utilization by muscle cells, resulting peripheral IR develops.…”

Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of high-fat diet-fed rats through AMP-activated protein kinase signaling

“…Skeletal muscle glucose uptake and metabolism play a key role in the regulation of whole-body glucose homeostasis in normal and diabetic subjects (10,11). Glucose uptake is the rate-limiting step of glucose utilization and is depressed in cases of insulin resistance, a process characterized by the reduced availability of sarcolemmal glucose transporter 4 (GLUT4) translocation and consequential lower glucose uptake (12,13).…”