Tyrosine kinase activity of skeletal muscle during insulin infusion in humans.
Insulin receptor tyrosine kinase is stimulated by insulin in vivo, and this provides a mechanism by which the signal from insulin is transmitted into target cells. This study examined the time course of the in vivo activation of the kinase. Five nondiabetic Pima Indians had a euglycemic clamp at an insulin dose of 600 mU/min.m2, resulting in plasma insulin concentrations of about 15 nM by 30 min. Percutaneous muscle biopsies were taken from the vastus lateralis before and at regular intervals during insulin infusion, and the in vivo and in vitro tyrosine kinase activities were measured. There was a rapid in vivo activation of the kinase, detectable at less than 10 min and reaching a maximum within 30 min of insulin infusion. The time course of in vivo kinase activity, plasma insulin concentrations, and insulin-mediated glucose disposal rates displayed parallel patterns, indicating close interrelationships among these variables. The insulin concentration at which the kinase activity was maximal was about 10 nM both in vivo and in vitro. In vitro, however, this maximum increased with the degree of the kinase activation in vivo, indicating that the kinase potential in vitro is dependent on previous insulin exposure in vivo. We conclude that in vivo activation of the insulin receptor tyrosine kinase in human skeletal muscle is a rapid process, related to insulin action on glucose disposal, and that circulating insulin primes inactive insulin receptor molecules for subsequent tyrosine kinase activation by a mechanism that remains to be elucidated.
Nyomba
B L
BL
Clinical Diabetes and Nutrition Section, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016.
Ossowski
V M
VM
Saad
M F
MF
Bogardus
C
C
Mott
D M
DM
D000328:Adult; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D009132:Muscles / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000502:physiology
D007328:Insulin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin