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Human Insulin Receptors Expressed in Insulin-Insensitive Mouse Fibroblasts Couple with Extant Cellular Effector Systems to Confer Insulin Sensitivity and Responsiveness^*

CECILIA HOFMANN, MORRIS F. WHITE and JONATHAN WHITTAKER

Research Service, Hines Veterans Administration Hospital (M.F. W.) Hines, Illinois 60141
Departments of Biochemistry and Surgery, Loyola University Stritch School of Medicine (M.F. W.) Maywood, Illinois 60153
Research Division, Joslin Diabetes Center (M.F. W.), and the Department of Medicine, Harvard Medical School (M.F. W.) Boston, MA 02215
Howard Hughes Medical Institute and the Department of Biochemistry and Molecular Biology, University of Chicago (J. W.) Chicago, Illinois 6

Address all correspondence and requests for reprints to: Cecilia Hofmann, Ph.D., Research Service 151 Z4, Hines Veterans Administration Hospital, Hines, Illinois, 60141.

Abstract

When cDNA for human kidney insulin receptors was used to transfect NIH3T3 mouse fibroblast cells with few or no endogenous insulin receptors, a resultant cell line, 3T3/ HIR, expressed more than 6 million receptors/cell. Results of the present study demonstrated that these human receptors in murine cells mediated a diverse group of responses, including insulin binding and internalization as well as insulin-stimulated tyrosine phosphorylation of the receptor and a putative cellular substrate ppl85. In addition, the cells were stimulated by insulin in various acute and long term metabolic processes, including glucose transport, glycogen formation, amino acid uptake, and thymidine uptake and incorporation into DNA. There were weak or no responses to insulin in control fibroblasts transfected only with the pSV2Neo plasmid containing a bacterial gene for neomycin resistance (3T3/NEO cells). These findings indicated that transfection of insulin receptor cDNA conferred insulin sensitivity to the target cells in a broad range of cellular responses and further demonstrated that effector molecules for mediating such responses were present in cells that normally lacked sensitivity to this hormone. Expressed receptors readily coupled with the effector systems to become fully functional. (Endocrinology 124: 257–264,1989)

Footnotes

^* This work was supported by grants from the American Diabetes Association (to C.H.), the Juvenile Diabetes Foundation (to C.H.), the V.A. Research Program (to C.H.), and the Howard Hughes Medical Institute (to J.W.) and FIRST Award DK-38712 (to M.F.W.).

Scholar of the PEW Foundation (Philadelphia, PA).

Received August 1, 1988.

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