Muscle fiber type specificity in insulin signal transduction.
We determined the muscle fiber type-specific response of intracellular signaling proteins to insulin. Epitrochlearis (Epi; 15% type I, 20% type IIa, and 65% type IIb), soleus (84, 16, and 0%), and extensor digitorum longus (EDL; 3, 57, and 40%) muscles from Wistar rats were incubated without or with 120 nM insulin (3-40 min). Peak insulin receptor (IR) tyrosine phosphorylation was reached after 6 (soleus) and 20 (Epi and EDL) min, with sustained activity throughout insulin exposure (40 min). Insulin increased insulin receptor substrate (IRS)-1 and IRS-2 tyrosine phosphorylation and phosphotyrosine-associated phosphatidylinositol (PI)-3-kinase activity to a maximal level after 3-10 min, with subsequent downregulation. Akt kinase phosphorylation peaked at 20 min, with sustained activity throughout insulin exposure. Importantly, the greatest insulin response for all signaling intermediates was observed in soleus, whereas the insulin response between EDL and Epi was similar. Protein expression of the p85alpha-subunit of PI 3-kinase and Akt kinase, but not IR, IRS-1, or IRS-2, was greater in oxidative versus glycolytic muscle. In conclusion, increased function and/or expression of key proteins in the insulin-signaling cascade contribute to fiber type-specific differences in insulin action in skeletal muscle.
Song
X M
XM
Department of Clinical Physiology, Gustaf V's Research Institute, Karolinska Hospital, S-171 76 Stockholm, Sweden.
Ryder
J W
JW
Kawano
Y
Y
Chibalin
A V
AV
Krook
A
A
Zierath
J R
JR
D000818:Animals; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000502:physiology*; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009928:Organ Specificity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D010750:Phosphoproteins; D019000:Phosphotyrosine; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin