TY - JOUR
T1 - Influence of changes in insulin receptor binding during insulin infusions on the shape of the insulin dose-response curve for glucose disposal in man
AU - Baker, B.
AU - Mandarino, L.
AU - Brick, B.
AU - Rizza, R.
AU - Gerich, J.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1984/2
Y1 - 1984/2
N2 - 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 each 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 × 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 ndicate 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.
AB - 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 each 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 × 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 ndicate 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.
UR - http://www.scopus.com/inward/record.url?scp=0021331831&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021331831&partnerID=8YFLogxK
U2 - 10.1210/jcem-58-2-392
DO - 10.1210/jcem-58-2-392
M3 - Comment/debate
C2 - 6363438
AN - SCOPUS:0021331831
SN - 0021-972X
VL - 58
SP - 392
EP - 396
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -