PMID: 7025901Jul 21, 1981Paper

Relationship between negative cooperativity and insulin action

Biochemistry
J M OlefskyH Tager

Abstract

We have compared the respective abilities of porcine insulin and [LeuB25]insulin to enhance the rate of dissociation of receptor-bound [125I]insulin from IM-9 lymphocytes and isolated rat adipocytes and to increase the rate of adipocyte glucose transport and oxidation. Although porcine insulin (100 ng/mL) greatly enhanced the dissociation rate of previously bound [125I]insulin, [LeuB25]insulin (at a concentration yielding equivalent receptor occupancy) had no effect. Nevertheless, the analogue fully stimulated adipocyte glucose transport and oxidation at concentrations consistent with its reduced (1.7% of normal) intrinsic binding affinity. Activation of glucose transport by the analogue was rapid, and the corresponding rate of activation was indistinguishable from that produced by native insulin. The increased dissociation rate observed with increasing receptor occupancy by native porcine insulin has been interpreted as evidence for negative cooperative site-site interactions between occupied receptors. According to this formulation, [LeuB25]insulin is a "noncooperative" insulin analogue. Since this [LeuB25]insulin retains full biologic activity, the enhancement of the insulin dissociation rate at high levels of receptor occup...Continue Reading

Citations

Sep 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·R K AssoianH S Tager
Apr 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·V Bonnevie-NielsenH S Tager
Jan 16, 1985·Biochemical and Biophysical Research Communications·N BegumJ Tepperman
May 31, 2014·Journal of Diabetes Science and Technology·W Kenneth WardRobert S Cargill
Aug 22, 2002·The Journal of Biological Chemistry·Daniel E Koshland, Kambiz Hamadani
Jan 1, 1982·CRC Critical Reviews in Biochemistry·T L BlundellS P Wood
Apr 1, 1986·The American Journal of Physiology·E C AlmiraB R Boshell

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