Evidence against high glucose as a mediator of ERK1/2 or p38 MAPK phosphorylation in rat skeletal muscle

Hyperglycemia leads to multiple changes in insulin signaling in skeletal mu scle from people with type 2 diabetes. We hypothesized that mitogen-activat ed protein kinase (MAPK) signaling cascades may be directly activated by an acute exposure to high extracellular glucose concentrations. We determined whether an elevation in the extracellular glucose concentration would indu ce signal transduction in skeletal muscle via MAPK cascades. Epitrochlearis muscles were incubated in the presence of 5 or 25 mM glucose. Exposure of muscle to either hyperosmosis (600 mM mannitol) or insulin (6 nM) led to a marked increase in extracellular signal-regulated protein kinase (ERK)1/2 p hosphorylation. Hyperosmosis elicited a 5.2-fold increase in p38 phosphoryl ation (P < 0.05), whereas insulin was without effect. ERK1/2 phosphorylatio n was not increased by high glucose exposure. After a 20-min exposure to 25 mM glucose, a tendency toward repressed (23%) p38 phosphorylation was obse rved (P = 0.06). No effect of high glucose was noted on signal transduction to signal transducer and activator of transcription 3 and Akt. In conclusi on, short-term exposure of skeletal muscle to high levels of glucose does n ot appear to alter ERK1/2 or p38 MAPK phosphorylation.