title: Potassium channel openers prevent palmitate-induced insulin resistance in C2C12 myotubes.
abstract: Insulin resistance (IR) of muscle cells is an early symptom of type 2 diabetes. It often results from excessive lipid accumulation in muscle fibers which under in vitro experimental conditions may be induced by incubation of muscle cells with palmitate. IR is manifested as a reduced response of cells to insulin expressed by lowered Akt kinase phosphorylation and decreased insulin-dependent glucose uptake. Stimulation of mitochondrial oxidative metabolism by mild dissipation of the mitochondrial potential is thought to increase fatty acid utilization and thereby prevent insulin resistance. Here it is shown that nicorandil and NS1619, which are openers of two different mitochondrial potassium channels, protect C2C12 myotubes from palmitate-induced insulin resistance. Preincubation of myotubes with 5-hydroxydecanoate abolishes the protective effect of nicorandil. The efficient concentrations of both openers are far below those commonly applied for cytoprotection. This is probably why their effects on the mitochondrial energy metabolism are small. These data suggest that opening of mitochondrial potassium channels could be a promising approach in prevention and therapy of insulin resistance related to dyslipidemia and obesity.
authors.affiliation: Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Dymkowska
authors.affiliation: Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Drabarek
authors.affiliation: Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Jakubczyk
authors.affiliation: Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Wojciechowska
authors.affiliation: Nencki Institute of Experimental Biology, Warsaw, Poland. Electronic address: k.zablocki@nencki.gov.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zabłocki
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002460:Cell Line; D007333:Insulin Resistance; D015640:Ion Channel Gating / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020108:Nicorandil / Q000494:pharmacology*; D010168:Palmitates / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D015221:Potassium Channels / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D010168:Palmitates; D015221:Potassium Channels; C086491:NS 1619; D020108:Nicorandil; D051057:Proto-Oncogene Proteins c-akt
keywords: C2C12 myotubes; Insulin resistance; NS1619; Nicorandil; Reactive oxygen species