Antagonistic effects of a covalently dimerized insulin derivative on insulin receptors in 3T3-L1 adipocytes

Journal Article · Thu Feb 01 04:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.3.1154· OSTI ID:6718510

Weiland, M; Joost, H G ^[1]; Brandenburg, C; Brandenburg, D ^[2]

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1. Institut fuer Pharmakologie and Toxikologie der Universitaet Goettingen (Germany, F.R.)
2. Deutsches Wollforschungsinstitut, Aachen (Germany, F.R.)

In the present study the authors describe the antagonistic effects of the covalently dimerized insulin derivative B29,B29{prime}-suberoyl-insulin on insulin receptors in 3T3-L1 mouse cells. In differentiated 3T3-L1 adipocytes, the derivative fully inhibits binding of {sup 125}I-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 (({sup 3}H)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{prime}-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.

• OSTI ID: 6718510
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:3; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
ANIMAL CELLS
AZINES
BETA DECAY RADIOISOTOPES
CARBOHYDRATES
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
CROSS-LINKING
DAYS LIVING RADIOISOTOPES
DERIVATIZATION
ELECTRON CAPTURE RADIOISOTOPES
FAT CELLS
FIBROBLASTS
GLUCOSE
HETEROCYCLIC COMPOUNDS
HEXOSES
HORMONES
HYDROGEN COMPOUNDS
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
MONOSACCHARIDES
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HORMONES
POLYMERIZATION
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RECEPTORS
RIBOSIDES
SACCHARIDES
SOMATIC CELLS
THYMIDINE
TRITIUM COMPOUNDS