Cell surface expression of LDL receptor is decreased in type 2 diabetic patients and is normalized by insulin therapy.
OBJECTIVE
In type 2 diabetic patients with poor metabolic control, kinetic studies have demonstrated that LDL fractional catabolic rate (FCR) is slowed down, whereas it is normalized on insulin therapy. This study was designed to analyze whether variations in the expression of LDL receptors at the cell surface could explain the results observed in kinetic studies.


METHODS
LDL receptors were quantified at the surface of mononuclear cells in fresh fasting blood samples by a flow cytometry method in 21 control subjects and 21 type 2 diabetic patients before and 3 months after the introduction of insulin therapy and concomitant removal of oral antidiabetic drugs.


RESULTS
Before insulin treatment, monocyte LDL receptor expression was reduced by 41% (6,439 +/- 2,310 vs. 10,846 +/- 2,764 receptors per monocyte, P < 0.001) in type 2 diabetic patients compared with control subjects. It increased by 57% after 3 months of insulin therapy (10,096 +/- 5,657 vs. 6,439 +/- 2,310, P < 0.01) and was similar to that observed in control subjects.


CONCLUSIONS
Our results suggest that insulin plays an important role in the in vivo expression of LDL receptors. Moreover, modulations in the expression of LDL receptors in type 2 diabetic patients either with poor metabolic control or on insulin therapy are likely to contribute to the variations of LDL FCR demonstrated by kinetic studies under those circumstances.
Duvillard
Laurence
L
Unity INSERM 498, Hôpital du Bocage, Dijon Cédex, France. laurence.duvillard@chu-dijon.fr
Florentin
Emmanuel
E
Lizard
Gérard
G
Petit
Jean-Michel
JM
Galland
Françoise
F
Monier
Serge
S
Gambert
Philippe
P
Vergès
Bruno
B
D000284:Administration, Oral; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011973:Receptors, LDL / Q000097:blood*; D012016:Reference Values; D017211:Treatment Failure; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011973:Receptors, LDL; D014280:Triglycerides; D002784:Cholesterol