Influence of changes in insulin receptor binding during insulin infusions on the shape of the insulin dose response curve for glucose disposal in man

B. Baker, L. Mandarino, B. Brick, R. Rizza, J. Gerich

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Abstract

To determine the influence of insulin infusions used in dose-response studies on monocyte insulin binding, monocyte insulin binding and glucose disposal were measured in six normal subjects before and at the end of four sequential 2-h insulin infusions (0.4, 1.0, 2.0, and 10 mU kg-1 min-1). Monocyte insulin binding was unaltered at the end of the first three infusions (plasma insulin, 31 ± 2 (SEM), 77 ± 3, and 184 ± 10 μU/ml) but was decreased after the last infusion (plasma insulin, 1730 ± 125 μU/ml) at 0.2 through 10.2 ng/ml insulin concentrations in the binding assay (P < 0.01). Using a one-site model, this could be ascribed to a decrease in insulin receptor affinity (1.54 ± 0.26 vs. 2.27 ± 0.48 x 108 M-1, P < 0.05), whereas in a two-site model this appeared to be due to a decrease in high affinity binding sites (1,868 ± 228 vs. 2,387 ± 207, P < 0.02). Nevertheless, insulin receptor occupancies estimated to occur during the insulin infusions were virtually identical whether preinsulin infusion binding data (745 ± 72, 1,383 ± 117, 2,572 ± 302, and 10,092 ± 1,708) or binding data at the end of each infusion (702 ± 56, 1,367 ± 150, 2,383 ± 318, and 9,158 ± 2,023) were used to calculate occupancy. These results indicate that although monocyte insulin binding decreased during dose-response experiments using sequential infusions of insulin, due to the concentrations of insulin at which this occurs this decrease did not alter the shape of the dose-response curve relating glucose disposal to monocyte insulin receptor occupancy.

Original languageEnglish (US)
Pages (from-to)392-396
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume58
Issue number2
StatePublished - 1984
Externally publishedYes

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Insulin Receptor
Insulin
Glucose
Monocytes
Plasmas
Assays
Binding Sites

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Influence of changes in insulin receptor binding during insulin infusions on the shape of the insulin dose response curve for glucose disposal in man. / Baker, B.; Mandarino, L.; Brick, B.; Rizza, R.; Gerich, J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 58, No. 2, 1984, p. 392-396.

Research output: Contribution to journalArticle

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AU - Gerich, J.

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