Studies on the Metabolism of Plasma Proteins in the Nephrotic Syndrome. Ii. The Lipoproteins12

Gitlin, David; Cornwell, David G.; Nakasato, Doris; Oncley, J. L.; Hughes, Walter L.; Janeway, Charles A.

doi:10.1172/jci103596

Cited by 249 publications

(46 citation statements)

References 23 publications

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“…In these patients, the correlation (r) value between glycohaemoglobin and glycoalbumin was 0.86, indicating that integrated glycaemia during the two weeks before sampling approximated that during the 2-3 months before sampling; in other words, patients with elevated glycohaemoglobin also had increased glycoalbumin concentrations, reflecting chronic and unchanged hyperglycaemia during the preceding 2 -10 weeks, whereas patients with normal glycohaemoglobin also had normal glycoalbumin concentrations, reflecting stability of glycaemic control during the preceding 2-10 weeks. Therefore, correlation of glycated LDL concentrations with these other indicators of integrated glycaemic control was sought, on the assumption that ambient glycaemia during the week before sampling (estimated circulating half-life of LDL is 3 -5 days (29)) in these subjects probably approximated that during the preceding 2-10 weeks. Figure 3 illustrates these correlations with r values of 0.67 between glycohaemoglobin and glycated LDL concentrations, and 0.77 between glycoalbumin and glycated LDL concentrations.…”

Section: Resultsmentioning

confidence: 99%

Glycated LDL Concentrations in Non-Diabetic and Diabetic Subjects Measured with Monoclonal Antibodies Reactive with Glycated Apolipoprotein B Epitopes

Cohen

Lautenslager²,

Shea³

1993

Clinical Chemistry and Laboratory Medicine

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Summary:The potential importance of the non^enzymatic glycation of low density lipoproteins (LDL) in atherogenesis and in the accelerated atherosclerosis associated with diabetes is well recognized. However, it has been difficult to evaluate LDL glycation in the clinical setting because of the lack of suitable methods. To approach this problem, we produced monoclonal antibodies, designated ES 12, that recognize glycated apolipoprotein B epitopes in the LDL complex in human plasma. Here we report the use of these antibodies in a competitive enzyme-linked imniunosorbent assay (ELISA) to measure glycated LDL concentrations in plasma from non-diabetic and diabetic subjects. In this assay, glycated LDL in the soluble phase inhibits binding of the ES 12 antibody to glycated LDL immobilized to microtitre wells, whereas other glycated proteins and non-glycated LDL do not compete. A linear dose-response relationship for 10 -125 ng glycated LDL per well allows the construction of standard curves, from which the concentration of glycated LDL in human plasma can be determined. The mean concentration of glycated LDL in samples from non-diabetic subjects was 21.8 + 0.9 mg/1, increasing to 40.8 ± 2.6 mg/1 in samples from patients with type II diabetes, comprising 1.9-4.8% and 3.2-14.8%, respectively, of total apolipoprotein B. Glycated LDL concentrations in samples from diabetic patients correlated positively and significantly with other indices of glycaemic status. The results indicate that circulating glycated LDL, which may have diagnostic and pathophysiologic importance, is increased in diabetes with attendant hyperglycaemia. The results further indicate that the described monoclonal antibody^based competitive ELISA affords a simple and reproducible method for quantitative measurement of glycated LDL. Introduction··.,,. ι · ι -siderable interest, because it has been implicated in Non-enzymatic glycation is a condensation reaction the premature and severe atherosclerosis associated between glucose and reactive protein amino groups with diabetes mellitus, and LDL glycation is one of at the NH 2 -terminus or e-amino groups of lysine the post-secretory modifications believed to affect its residues. In diabetic subjects, hyperglycaemia pro-atherogenic potential. For example, internalization motes increased non-enzymatic glycation of circulat-and degradation by cultured fibroblasts of LDL from ing and tissue proteins, thereby allowing assessment patients with insulin-dependent diabetes and poor of integrated glycaemic control through determina-metabolic control is decreased, compared with that tion of glycohaemoglobin and glyco lbumin concen-of LDL isolated from normal subjects or from patrations, and also providing insight into pathogenetic tients with insulin-dependent diabetes and good metmechanisms associated with chronic complications of abolic control (1). Glycation of LDL diminishes the diabetes. The non-enzymatic glycation of apolipopro-high affinity LDL receptor-mediated uptake and deteinB, the principal protein of the ...

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Section: Resultsmentioning

confidence: 99%

Glycated LDL Concentrations in Non-Diabetic and Diabetic Subjects Measured with Monoclonal Antibodies Reactive with Glycated Apolipoprotein B Epitopes

Cohen

Lautenslager²,

Shea³

1993

Clinical Chemistry and Laboratory Medicine

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“…To be of use, tracers must have certain properties: they must be detectable with adequate sensitivity; they must not perturb the system under investigation; and they must be metabolically indistinguishable from the tracee. The earliest lipoprotein kinetics studies used radioiodinated tracers exogenously attached to lipoproteins to trace VLDL metabolism (19,20). Since 1985, when Cryer et al (21) first reported the use of endogenous labeling with [ 15 N]glycine, the use of exogenous labeling for kinetics studies has declined.…”

Section: Labeling Methodsmentioning

confidence: 99%

Thematic review series: Patient-Oriented Research. Design and analysis of lipoprotein tracer kinetics studies in humans

Barrett

Chan

Watts

2006

Journal of Lipid Research

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Lipoprotein tracer kinetics studies have for many years provided new and important knowledge of the metabolism of lipoproteins. Our understanding of kinetics defects in lipoprotein metabolism has resulted from the use of tracer kinetics studies and mathematical modeling. This review discusses all aspects of the performance of kinetics studies, including the development of hypotheses, experimental design, statistical considerations, tracer administration and sampling schedule, and the development of compartmental models for the interpretation of tracer data. In addition to providing insight into new metabolic pathways, such models provide quantitative information on the effect of interventions on lipoprotein metabolism. Compartment models are useful tools to describe experimental data but can also be used to aid in experimental design and hypothesis generation. The SAAM II program provides an easy-to-use interface with which to develop and test compartmental models against experimental models. The development of a model requires that certain checks be performed to ensure that the model describes the experimental data and that the model parameters can be estimated with precision.In addition to methodologic aspects, several compartment models of apoprotein and lipid metabolism are reviewed. Years of clinical investigation have provided valuable insight into the complexity of human lipoprotein metabolism. The measurement of plasma lipoprotein concentrations provides useful information, but from a functional viewpoint these concentrations reflect the balance between input and output in the lipoprotein system in plasma. The only way to quantify input and output in this system is by undertaking kinetics studies, typically using tracer methodology. These studies, however, are time-consuming and difficult to perform. Nevertheless, they are important to characterize the pathways that result in dyslipidemic states and to describe the in vivo mechanisms of action of treatments designed to regulate dyslipidemia and cardiovascular disease risk in clinical practice. There are many steps to consider when planning such metabolic studies. This review touches on all aspects of the design and analysis of lipoprotein kinetics studies, including philosophical angles, tracer methodology, mathematical modeling, and statistical considerations related to experimental design and analysis.With the advent of commercial stable isotopes and endogenous labeling protocols, some aspects of performing kinetics studies are now easier than when radioactive tracers and laborious exogenous labeling of lipoproteins were required. However, the number of laboratories and research groups undertaking these types of metabolic studies has changed little, highlighting the complexity of the methods involved.In addition to the design and modeling aspects of lipoprotein kinetics studies, what we have learned from apolipoprotein B (apoB) and HDL apoA-I and apoA-II tracer kinetics studies is covered in the present series of reviews by Parhofer and Barret...

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“…Such relationships are of particular interest for very low density (VLDL)1 and low density lipoproteins (LDL), since the existence of a precursor-product relationship between the two has been suggested. Shared apoprotein antigens (1,2) and the appearance of radioiodinated, injected VLDL protein in LDL (3,4), have led to the hypothesis that some, if not all, of the plasma LDL arises from VLDL catabolism (3,4).…”

Section: Introductionmentioning

confidence: 99%

Metabolic relationships among the plasma lipoproteins

Wilson¹,

Lees²

1972

J. Clin. Invest.

278

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A B S T R A C T The changes in other plasma lipoproteins which accompany alterations in very low density lipoproteins (VLDL) were studied in 31 normal and hyperlipidemic men and women who underwent weight reduction, carbohydrate induction, or clofibrate treatment. Plasma lipids and individual lipoprotein cholesterol concentrations were measured serially during control and treatment periods. Low density lipoprotein (LDL) protein was determined by radial immunodiffusion. Oppositely directed changes in VLDL and LDL were found with each of the three metabolic perturbations. Changes in high density lipoprotein (HDL) cholesterol generally paralleled those in LDL but were less consistent. Two patients with type III hyperlipoproteinemia failed to demonstrate reciprocal increases in LDL despite more than 40% reduction in plasma glycerides or VLDL with weight reduction or clofibrate therapy. After clofibrate therapy, LDL increased in proportion to the absolute decrease in VLDL cholesterol during treatment. LDL protein changed relatively less than did LDL cholesterol. The mechanism for the interdependency of plasma VLDL and LDL concentrations over the long term is not known and may be the result of altered rates of interconversion of these lipoproteins, or to feedback inhibition by VLDL of LDL production and release.

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Studies on the Metabolism of Plasma Proteins in the Nephrotic Syndrome. Ii. The Lipoproteins12

Cited by 249 publications

References 23 publications

Glycated LDL Concentrations in Non-Diabetic and Diabetic Subjects Measured with Monoclonal Antibodies Reactive with Glycated Apolipoprotein B Epitopes

Glycated LDL Concentrations in Non-Diabetic and Diabetic Subjects Measured with Monoclonal Antibodies Reactive with Glycated Apolipoprotein B Epitopes

Thematic review series: Patient-Oriented Research. Design and analysis of lipoprotein tracer kinetics studies in humans

Metabolic relationships among the plasma lipoproteins

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