Monoclonal antibodies to the insulin receptor mimic metabolic effects of insulin but do not stimulate receptor autophosphorylation in transfected NIH 3T3 fibroblasts

Journal Article · Sat Jul 01 04:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.14.5217· OSTI ID:5442978

Soos, M A; O'Brien, R M; Brindle, N P.J.; Stigter, J M; Okamoto, A K; Whittaker, J; Siddle, K ^[1]

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1. Univ. of Cambridge (England)

The metabolic actions of insulin and anti-insulin receptor monoclonal antibodies were compared with their effects on insulin receptor phosphorylation in mouse NIH 3T3 fibroblasts transfected with human insulin receptor cDNA. In serum-starved NIH 3T3 HIR3.5 cells, uptake of 2-deoxy-({sup 3}H)glucose was stimulated up to 2-fold after 30 min with insulin, with a half-maximal effect at 0.1 nM insulin. Incorporation of ({sup 3}H)thymidine was stimulated {approx} 12-fold after a 16-hr preincubation with insulin, with a half-maximal effect at 2 nM insulin. Phosphorylation of insulin receptor {beta}-subunit in cells prelabeled with ({sup 32}P)phosphate was increased 10- to 20-fold within 5 min of adding insulin. Monoclonal antibodies reacting with four different epitopes on the insulin receptor mimicked the effect of insulin on 2-deoxyglucose uptake. These antibodies also stimulated thymidine incorporation, although the maximum stimulation was only {approx} 30% that of insulin. It is concluded that the insulin-like metabolic effects of antibodies involve a mechanism of receptor activation that is independent of autophosphorylation and hence that receptor autophosphorylation is not an essential step in triggering at least some events in the insulin signaling pathway.

• OSTI ID: 5442978
• 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. 86:14; 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
ANIMALS
ANTIBODIES
AUTORADIOGRAPHY
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
CARBOHYDRATES
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
FIBROBLASTS
GLUCOSE
HETEROCYCLIC COMPOUNDS
HEXOSES
HORMONES
HYDROGEN COMPOUNDS
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
MICE
MONOCLONAL ANTIBODIES
MONOSACCHARIDES
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HORMONES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORYLATION
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RADIORECEPTOR ASSAY
RECEPTORS
RIBOSIDES
RODENTS
SACCHARIDES
SOMATIC CELLS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES