Direct method for detection and characterization of cell surface receptors for insulin by means of 125I-labeled autoantibodies against the insulin receptor.

Jarrett, David B.; Roth, Jesse; Kahn, C. Ronald; Flier, J. S.

doi:10.1073/pnas.73.11.4115

Cited by 70 publications

(32 citation statements)

References 23 publications

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“…We inquired whether the leftward shift of the binding-competition curves is specific for insulin and insulin analogs. In the case of antibodies to the insulin receptor, another ligand for the receptor (14), the leftward shift of the binding curve was not observed. Anti-receptor antibodies appeared to recognize insulin receptors equally well from all cell types studied (Fig.…”

Section: Introductionmentioning

confidence: 89%

Defect in cooperativity in insulin receptors from a patient with a congenital form of extreme insulin resistance.

Taylor¹,

Leventhal²

1983

J. Clin. Invest.

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Section: Introductionmentioning

confidence: 89%

Defect in cooperativity in insulin receptors from a patient with a congenital form of extreme insulin resistance.

Taylor¹,

Leventhal²

1983

J. Clin. Invest.

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“…Second, serum from patient B-7 and control serum were precipitated with ammonium sulfate (33% final concentration), the precipitate redissolved in phosphate buffer (0.01 M KH2PO4, pH 8), and dialyzed for 24 h in phosphate buffer, using dialysis tubing with a 3,500 D cutoff range. The retained material was concentrated and iodinated with 1251I using chloramine T oxidation to a final specific activity of 10-15 ,Ci/Mg protein as previously described by Jarrett et al (21). Additionally, the ammonium sulfate precipitates were further resolved on DEAE ion exchange chromatography according to the procedure of Jarrett et al (21).…”

Section: Heart Perfusion Andfixationmentioning

confidence: 99%

“…The retained material was concentrated and iodinated with 1251I using chloramine T oxidation to a final specific activity of 10-15 ,Ci/Mg protein as previously described by Jarrett et al (21). Additionally, the ammonium sulfate precipitates were further resolved on DEAE ion exchange chromatography according to the procedure of Jarrett et al (21). The DEAE-purified material was also concentrated, iodinated with '25I to a specific activity of - [10][11][12][13][14][15] ,MCi/Mg protein.…”

Section: Heart Perfusion Andfixationmentioning

confidence: 99%

Vascular transport of insulin to rat cardiac muscle. Central role of the capillary endothelium.

Bar

Boes²,

Sandra³

1988

J. Clin. Invest.

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Using intact, beating hearts, we have assessed the interaction of insulin with capillary endothelium and the subsequent appearance of insulin in cardiac muscle. Rat hearts were perfused with '25I-insulin (10`0 M) alone or in combination with unlabeled insulin (10-9-10-5 M). 125I grains (shown to represent > 90% intact insulin) over both capillary endothelium and cardiac muscle decreased in a dose-dependent manner when hearts were co-perfused with labeled insulin and increasing concentrations of unlabeled insulin. Perfusion of 125I-desoctapeptide (DOP) insulin, a low affinity insulin analogue, with unlabeled insulin (10-9-10-5 M) had no effect on the appearance of 125I-DOP insulin over microvessel endothelium and muscle. When capillary receptors were first destroyed by trypsin treatment or blocked by anti-receptor antibodies, the appearance of 125I-insulin in cardiac muscle decreased proportional to the inhibition of insulin binding to the capillary receptors. We conclude that insulin binding to capillary endothelial receptors is a central step in the transport of intravascular insulin to rat cardiac muscle.

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“…In a previous report, we have shown that the circulating inhibitors in these patients are polyclonal immunoglobulins, primarily of the IgG class, and that their inhibitory activity is mediated through the F(ab')2 portion of the molecule (3). Further, several lines of evidence strongly suggest that these antibodies act by binding directly to determinants on, or intimately linked to, the insulin receptor molecule (2)(3)(4). Thus, these immunoglobulins may be considered to be "antireceptor antibodies" such as those which have been proposed as etiologic factors in Graves' disease (5) and myasthenia gravis (6).…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies to the Insulin Receptor

Flier¹,

Kahn²,

Jarrett³

et al. 1977

J. Clin. Invest.

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A B S T R A C T The serum of some patients with insulin-resistant "diabetes" contains antibodies that bind to and block the cell membrane receptors for insulin. In this report, we have characterized the effects of the antireceptor antibodies on the interaction of 125I-insulin with its receptor on the human lymphoblastoid cell line IM-9. Up to 95% of specific insulin binding can be inhibited by pretreatment of the cells with these immunoglobulins. The onset of the inhibitory effect is time-and temperature-dependent, and the effect is reversed extremely slowly if the cells are suspended in a large excess of antibody-free buffer. These features of antibody binding can be easily distinguished from those for insulin binding to its receptor. The inhibitory effect of the antibodies can be reversed by exposure of the cells to conditions known to elute surface immunoglobulins.The three antireceptor sera studied appear to alter the insulin-receptor interaction in different ways. Two antisera markedly reduce receptor affinity through combined effects on the insulin association and dissociation rates, and, additionally, have smaller effects on available receptor number. A third antiserum primarily affects available receptor number and has little effect on receptor affinity. All three antisera inhibit the capacity of insulin to promote negatively cooperative site-site interactions among insulin a receptors. The data suggest that these autoantibodies to the insulin receptor bind to different determinants on the receptor and may therefore be useful as

show abstract

Direct method for detection and characterization of cell surface receptors for insulin by means of 125I-labeled autoantibodies against the insulin receptor.

Abstract: Autoantibodies directed against the cell surface receptors for insulin are found in some patients with extreme insulin resistance.

Cited by 70 publications

References 23 publications

Defect in cooperativity in insulin receptors from a patient with a congenital form of extreme insulin resistance.

Defect in cooperativity in insulin receptors from a patient with a congenital form of extreme insulin resistance.

Vascular transport of insulin to rat cardiac muscle. Central role of the capillary endothelium.

Autoantibodies to the Insulin Receptor

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