Apo B-containing lipoprotein particles in poorly controlled insulin-dependent diabetes.
The goal of this study was to compare the structural and biological characteristics of apolipoprotein (apo) B-100-containing particle subfractions isolated from poorly controlled diabetic patients with insulin-dependent diabetes (IDDM), and healthy controls matched for sex, age and body mass index (BMI). Different apo B-containing particles were isolated by sequential immunochromatography and were free of apo A-I, apo A-II, apo A-IV and apo(a). Particles lipoprotein (Lp) B/C-III contained apo B and apo C-III. They were free of apo E. Particles Lp B/E contained apo B and apo E. They were free of apo C-III. Particles Lp B were devoided of apo C-III and apo E. All these particles could contain other known apolipoproteins not cited here, as for example apo C-II and/or apo C-I. The plasma levels of cholesterol, triglycerides, phospholipids, apo A-I, B-100, C-III, E, total Lp B/C-III, total Lp B/E were not different between patients and controls. The physico-chemical properties of Lp B/C-III and Lp B/E were similar in both groups. Only Lp B from patients exhibited some changes, an increase in the size and a decrease in the cholesterol and cholesteryl ester levels. The conformational properties of the lipoproteins were studied through their immunoreactivity against four different anti-apo B-100 monoclonal antibodies (MAb) for which sequential epitopes have been located on the protein, and one MAb for which the epitope is conformationally expressed. Again, minor changes were observed between patients and controls, and only a slight decrease in the immunoreactivity of the epitope encompassing amino-acid residues 405 to 539 of Lp B and of the conformationally expressed epitope of Lp B/C-III were found in patients. Nevertheless, whatever these conformational and/or physico-chemical modifications may be, they were not sufficient to induce functional alterations in the binding of the particles from the patients to the LDL-receptor of HeLa cells. This study shows that IDDM is not associated with any significant abnormalities in the apo-containing lipoprotein particles. The excessive occurrence of coronary heart disease (CHD) and other atherosclerotic vascular disease in patients with IDDM must have other causes.
Igau
B
B
SERLIA et INSERM U325, Institut Pasteur, Lille, France.
Lestavel
S
S
Clavey
V
V
Slomianny
C
C
Drouin
P
P
Bresson
R
R
Fruchart
J C
JC
Duriez
P
P
Fiévet
C
C
D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000032:analysis*; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology; D001786:Blood Glucose / Q000032:analysis; D003327:Coronary Disease / Q000209:etiology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D005260:Female; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000378:metabolism
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins; D011973:Receptors, LDL