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 muscle from people with type 2 diabetes. We hypothesized that mitogen-activated 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 induce 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 phosphorylation. Hyperosmosis elicited a 5.2-fold increase in p38 phosphorylation (P < 0.05), whereas insulin was without effect. ERK1/2 phosphorylation was not increased by high glucose exposure. After a 20-min exposure to 25 mM glucose, a tendency toward repressed (23%) p38 phosphorylation was observed (P = 0.06). No effect of high glucose was noted on signal transduction to signal transducer and activator of transcription 3 and Akt. In conclusion, short-term exposure of skeletal muscle to high levels of glucose does not appear to alter ERK1/2 or p38 MAPK phosphorylation.
Kawano
Y
Y
Department of Clinical Physiology, Karolinska Hospital, S-171 76 Stockholm, Sweden.
Ryder
J W
JW
Rincon
J
J
Zierath
J R
JR
Krook
A
A
Wallberg-Henriksson
H
H
D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009994:Osmolar Concentration; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D001786:Blood Glucose; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases