title: Dynamic changes in plasma proinsulin/insulin ratio during insulin secretion influence correlation between radioimmunoassay (RIA) and IMX measurements of insulin.
abstract: Because proinsulin and insulin have different circulatory half-lives, the ratio of proinsulin to insulin in plasma depends on the dynamics of insulin secretion. This variation can potentially influence comparison of IMX assays and radioimmunoassays (RIAs) for [insulin], given that the antibody used in the IMX assay has negligible cross-reactivity with proinsulin compared to the 40% cross-reactivity with proinsulin of the antibody used in the RIA. Simulation of a simple mass balance model for insulin and proinsulin concentrations during an oral glucose tolerance test predicts that the ratio (R) of RIA to IMX insulin measurements of [insulin] should transiently decrease, pass through a minimum, increase past the initial value, pass through a maximum and eventually return to the initial value. Using time course specimens from patients, this pattern of variation in R was observed in the majority (12/16) of cases studied. The variation in R for time course specimens (CV = 26%) was significantly greater than for other specimens (fasting, random or undesignated; P < 0.05). Thus, when comparing IMX and RIA measurements of [insulin], variation in R for samples from differing states of dynamic insulin secretion contains a component that is attributable to dynamic changes in the ratio of [proinsulin]/[insulin] in plasma.
authors.affiliation: Department of Pathology, Brooke Army Medical Center, Fort Sam Houston, TX, USA. douglas.stickle@amedd.army.mil
authors.forename: D F
authors.initials: DF
authors.lastname: Stickle
authors.forename: M A
authors.initials: MA
authors.lastname: Reynolds
authors.forename: M D
authors.initials: MD
authors.lastname: Morris
authors.forename: M J
authors.initials: MJ
authors.lastname: Quon
mesh_terms: D005951:Glucose Tolerance Test; D006801:Humans; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D011384:Proinsulin / Q000097:blood*; D011863:Radioimmunoassay
chemical_list: D007328:Insulin; D011384:Proinsulin