Dissection of the growth versus metabolic effects of insulin and insulin-like growth factor-I in transfected cells expressing kinase-defective human insulin receptors
| Autor: | Jerrold M. Olefsky, Donald A. McClain, Hiroshi Maegawa, R S Thies |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment GRB10 Stimulation Cell Biology Biology medicine.disease Biochemistry Insulin-like growth factor Insulin receptor Endocrinology Insulin resistance Internal medicine Insulin receptor substrate medicine biology.protein Growth factor receptor inhibitor Receptor Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 265:1678-1682 |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/s0021-9258(19)40069-0 |
| Popis: | We have recently reported that the expression of an in vitro mutated, kinase-defective insulin receptor (A/K1018) leads to cellular insulin resistance when expressed in Rat 1 fibroblasts. That is, despite the presence of normal numbers of activatable native insulin receptors in the host cell, the A/K1018 receptors prevent the normal receptors from phosphorylating endogenous substrates and from signalling insulin action, perhaps by competing for limiting amounts of these substrates. We report here that insulin-like growth factor I-stimulated phosphorylation of two endogenous substrate proteins, pp220 and pp170, is also inhibited in cells expressing A/K1018 receptors. Because insulin-like growth factor I stimulation of glucose uptake is not inhibited in cells with A/K1018 receptors while pp220 and pp170 phosphorylation is inhibited, it is unlikely that either pp220 or pp170 are involved in mediating the stimulation of glucose transport. In contrast, insulin-like growth factor I-mediated stimulation of mitogenesis is inhibited in cells with A/K1018 receptors. Thus, pp170 or pp220 could be involved in mitogenic signalling. We also report that both H2O2 and tetradecanoylphorbolacetate stimulate glucose transport normally in cells with A/K1018 receptors. Phorbol esters also lead to the phosphorylation of both normal and A/K1018 receptors on serine and/or threonine. This argues that phorbol esters or H2O2 bypass the normal proximal steps in signalling insulin action. |
| Databáze: | OpenAIRE |
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