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Insulin and Insulin-Like Growth Factor I Regulate the Same Biological Functions in HEP-G2 Cells Via Their Own Specific Receptors^*

E. J. VERSPOHL, B. A. MADDUX and I. D. GOLDFINE

Cell Biology Laboratory and Department of Medicine, Mount Zion Hospital and Medical Center San Francisco, California 94115
The Departments of Medicine and Physiology, University of California San Francisco, California 94143

Address requests for reprints to: Ira D. Goldfine, Cell Biology Laboratory, Mount Zion Hospital and Medical Center, P.O. Box 7921, San Francisco, California 94120.

The receptors for insulin and insulin-like growth factor I (IGF-I) are closely related molecules, with an extracellular binding domain and an intracellular tyrosine kinase domain. The interaction of insulin and IGF-I with their respective receptors activates the receptor kinase domain, leading to the biological actions of the hormones. Since insulin generally regulates metabolic events and IGF-I generally regulates growth events, it is believed that structural differences in the tyrosine kinase domains of the two respective receptors may elicit different biological responses via different transmembrane signaling mechanisms. We studied the regulation of glycogen metabolism and amino acid uptake in human cultured HEP-G2 hepatoma cells, which have distinct receptors for both insulin and IGF-I. The receptor specificity of these responses was probed with specific monoclonal antibodies to both the insulin and IGFI receptors. Stimulation of both [³H] glucose incorporation into glycogen and -[³H]aminoisobutyric acid uptake by insulin was half-maximal at concentrations of 1–5 nmol/L. These effects were blocked by the insulin receptor monoclonal antibody MA- 10, but not by the IGF-I receptor antibody aIR-3. Stimulation of both functions by IGF-I was half-maximal at concentrations of 1–5 nmol/L, and these effects were inhibited by aIR-3, but not by MA-10. These studies indicate that in HEP-G2 cells both insulin and IGF-I, via their own receptors, stimulate the same biological responses

^* This work was supported by NIH Grant DK-26667; the Elise Stern Haas Fund; the Department of Medicine, Mount Zion Hospital and Medical Center; and the Deutsche Forschungsgemeinschaft, West Germany.

Visiting Scientist from the Department of Pharmacology, University of Tuebingen, West Germany.

Received December 3, 1987.

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