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,
YEHIEL ZICK
,
JESSE ROTH and
SIMEON I. TAYLOR
Diabetes Branch, National Institute of Arthritis, Diabetes, Digestive, and Kidney Diseases, National Institutes of Health , Bethesda, Maryland 20205
Address all correspondence and requests for reprints to: Dr. Simeon I. Taylor, Diabetes Branch, National Institute of Arthritis, Diabetes, Digestive, and Kidney Diseases, Building 10, Room 8N-250, National Institutes of Health, Bethesda, Maryland 20205.
Insulin-stimulated phosphorylation of the insulin receptor was studied in cultured B-lymphocytes transformed by Epstein-Barr virus. In studies with cell lines derived from six normal subjects, insulin (10-7 M) caused an average increase of approximately 200
in 32P incorporation into the 95K subunit of the insulin receptor. Phosphorylation was rapid (detectable within 1–2 min) and reached a maximum level by 15 min. Doseresponse curves for receptor occupancy and phosphorylation were nearly superimposable, indicating few or absent spare receptors for this response to insulin. These data suggest that insulin receptor phosphorylation is an early response to insulin in cultured lymphocytes transformed with Epstein-Barr virus.
We studied insulin receptor phosphorylation in cell lines derived from nine patients with clinical syndromes associated with extreme insulin resistance, all of whom had normal [126I] insulin binding. While the magnitude of insulins stimulation varied widely among the individual cell lines, no significant differences were found between cell lines from normal subjects and those from patients with extreme insulin resistance.
* Presented in part at the 43rd Annual Meeting of the American Diabetes Association, San Antonio, TX, 1983. This work was partially supported by the American Diabetes Association, Inc., through a Roger Staubach Research Feasibility Grant to S.I.T.
Fogarty International Research Fellow (F05TW03126-02) on leave from the Department of Clinical Biochemistry and Human Metabolism, University of Newcastle, United Kingdom.
Department of Chemical Immunology, Weizmann Institute, Rehovot, Israel. Fulbright Scholar and recipient of a Chaim Weizmann Postdoctoral Fellowship.
Received April 10, 1984.
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T Kadowaki, C. Bevins, A Cama, K Ojamaa, B Marcus-Samuels, H Kadowaki, L Beitz, C McKeon, and S. Taylor Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance Science, May 6, 1988; 240(4853): 787 - 790. [Abstract] [PDF] |
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