In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 87, No. 3 ( 1990-02), p. 1154-1158
Abstract:
In the present study we describe the antagonistic effects of the covalently dimerized insulin derivative B29,B29'-suberoyl-insulin on insulin receptors in 3T3-L1 mouse cells. In differentiated 3T3-L1 adipocytes, the derivative fully inhibits binding of 125I-labeled insulin to its receptor with about the same affinity as unlabeled insulin. In contrast, the dimerized derivative only partially (approximately 20%) mimics insulin's effects on glucose transport and DNA synthesis in the absence of insulin. In the presence of insulin, the agent competitively inhibits insulin-stimulated DNA synthesis ([3H]thymidine incorporation into total DNA), glucose transport activity (2-deoxyglucose uptake rate), and insulin receptor tyrosine kinase activity. In rat adipocytes, in contrast, the dimerized derivative stimulates glucose transport (initial 3-O-methylglucose as well as 2-deoxyglucose uptake rates) to the same extent as insulin does, and it fails to inhibit the effect of insulin. The data indicate that the dimerized insulin derivative B29,B29'-suberoyl-insulin is an insulin receptor antagonist (partial agonist) which retains a moderate intrinsic activity. The effects of this agent reveal a striking difference in insulin receptor-mediated stimulation of glucose transport between 3T3-L1 fatty fibroblasts and the mature rat adipocyte.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.87.3.1154
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1990
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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