New PDF release: Biological Response Mediators and Modulators. John Jacob

February 27, 2018 | Development | By admin | 0 Comments

By J. Thomas August

ISBN-10: 0120680505

ISBN-13: 9780120680504

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Extra info for Biological Response Mediators and Modulators. John Jacob Abel Symposia on Drug Development

Sample text

3T3-L1 adipocytes were maintained in medium with or without 1 μΜ insulin for 24 h and then shifted to similar medium containing heavy (>95% 15 N-, 1 3 C-, 2H-) amino acids. The 24-h treatment with insulin caused a 55% and 60% down-regulation of cell surface and total (Triton X-100 extractable) cellular insulin receptor number. At various intervals after the densityshift, cell surface insulin receptors were covalently labeled with 1 2 *Iinsulin by the DSS cross-linking procedure and heavy and light labeled receptors separated.

Appearance of newly-synthesized active receptor at the plasma mem­ brane; rather, the ligand increases the net rate of loss of receptor from the cell surface. 33 3 Regulation of Insulin Receptor Metabolism Discussion Since the number of receptors a cell possesses in the steady-state is determined by the relative rates of synthesis and decay (k / k j of active receptor, ligand-induced changes in either of the rate constants for these processes could cause receptor down-regulation. In this paper, it is shown definitively that receptor down-regulation in 3T3-L1 adipocytes is the consequence of an insulin-induced increase in the rate of decay/inactivation of active receptor.

5). 80 w H—n—i i HTëhr- 1". y l Ohr+B 12 M F b70 X 60 E 50 Q. "40 1 30 g 20 10 | 50 V 40 m 30 00 I OhrlH I CVJ - 20 10 10 20 30 40 10 20 30 40 10 20 30 40 10 20 30 40 10 20 30 40 10 20 30 40 Fraction Number 3 Regulation of Insulin Receptor Metabolism 21 The levels of insulin-binding activity associated with the previouslysynthesized light and newly-synthesized heavy receptor peaks were quantitated by 125 I-insulin binding assays performed on fractionated CsCl isopycnic density-gradients. Figure 5 shows the progress curves for light receptor decay and heavy receptor synthesis.

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Biological Response Mediators and Modulators. John Jacob Abel Symposia on Drug Development by J. Thomas August


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