The carboxy terminal 110 amino acid portion of the insulin receptor is important for insulin signalling to pyruvate dehydrogenase.
Insulin-like growth factor 1 (IGF-1) had no detectable effect on pyruvate dehydrogenase (PDH) in NIH 3T3 cells that stably overexpressed normal human IGF-1 receptors. Insulin stimulated PDH activity 3-4--fold in cells that overexpressed normal human insulin receptors, but not in cells expressing TMI receptors, composed of the ligand binding domain of the insulin receptor coupled to the transmembrane and intracellular components of the IGF-1 receptor, or CEX receptors, in which the carboxy terminal 110 amino acid portion of the insulin receptor was exchanged for the corresponding portion of the IGF-1 receptor. In contrast, insulin stimulated glucose uptake in the control cell line and in each of the chimeric receptor-expressing lines with similar dose-response characteristics. These findings suggest the carboxy terminal portion of the IR may play a role in mediating the stimulation of PDH activity.
Gottschalk
W K
WK
Department of Biochemistry, University of Tennessee Center for Health Sciences, College of Medicine, Memphis 38163.
Lammers
R
R
Ullrich
A
A
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D005947:Glucose