Effect of IGF-I on phosphatidylinositol 3-kinase in soleus muscle of lean and insulin-resistant obese mice.
Insulin and IGF-I induced a similar stimulation of glucose transport in isolated soleus muscle. These actions require phosphatidylinositol (PI) 3-kinase activation since the PI 3-kinase inhibitor, wortmannin, blocked the stimulation by both peptides. We compared IGF-I with insulin in the ability to activate PI 3-kinase in the isolated soleus muscle from lean and gold thioglucose-induced obese insulin-resistant mice. In muscles from lean mice, IGF-I and insulin were able to activate PI 3-kinase with a similar time course, the effects being maximal within 3-5 min of stimulation. However, the IGF-I concentrations required to obtain similar effects on PI 3-kinase were about 10 times higher than the corresponding insulin doses. To determine through which receptor IGF-I was activating PI 3-kinase, the ability of IGF-I to activate both its own receptor and insulin receptor was simultaneously measured. Whatever the dose used (100 or 500 nmol/l), IGF-I activated to a nearly similar extent both the tyrosine kinase activity of its own receptor and that of the insulin receptor, suggesting that IGF-I was not only activating its receptor but was also able to stimulate the insulin receptor kinase. In muscles of obese insulin-resistant mice, although the defect of PI 3-kinase activation in response to IGF-I was relatively less pronounced (45%) than in response to insulin (70%) when compared with lean mice, PI 3-kinase stimulation was still markedly altered in response to IGF-I.
Jullien
D
D
Institut National de la Santé et de la Recherche Médicale, Faculty ofMedicine, Nice, France.
Heydrick
S J
SJ
Gautier
N
N
Van Obberghen
E
E
Le Marchand-Brustel
Y
Y
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D006051:Aurothioglucose; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000201:enzymology*; D009765:Obesity / Q000139:chemically induced / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D012016:Reference Values; D000077191:Wortmannin
D000730:Androstadienes; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D006051:Aurothioglucose; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D020794:Receptor Protein-Tyrosine Kinases; D000077191:Wortmannin