| Authors |
Goldberg IJ, Hu Y, Noh HL, Wei J, Huggins LA, Rackmill MG, Hamai H, Reid BN,
Blaner WS, Huang LS
|
| Submitted By |
Ira Goldberg on 2/8/2009 |
| Status |
Published |
| Journal |
Diabetes |
| Year |
2008 |
| Date Published |
6/1/2008 |
| Volume : Pages |
57(6) : 1674 - 1682 |
| PubMed Reference |
18346984 |
| Abstract |
OBJECTIVE: Patients with diabetes often have dyslipidemia and increased
postprandial lipidmia. Induction of diabetes in LDL receptor (Ldlr(-/-))
knockout mice also leads to marked dyslipidemia. The reasons for this are
unclear. RESEARCH DESIGN AND METHODS: We placed Ldlr(-/-) and heterozygous LDL
receptor knockout (Ldlr(+/-)) mice on a high-cholesterol (0.15%) diet, induced
diabetes with streptozotocin (STZ), and assessed reasons for differences in
plasma cholesterol. RESULTS: STZ-induced diabetic Ldlr(-/-) mice had plasma
cholesterol levels more than double those of nondiabetic controls.
Fast-performance liquid chromatography and ultracentrifugation showed an
increase in both VLDL and LDL. Plasma VLDL became more cholesterol enriched, and
both VLDL and LDL had a greater content of apolipoprotein (apo)E. In LDL the
ratio of apoB48 to apoB100 was increased. ApoB production, assessed using
[(35)S]methionine labeling in Triton WR1339-treated mice, was not increased in
fasting STZ-induced diabetic mice. Similarly, postprandial lipoprotein
production was not increased. Reduction of cholesterol in the diet to normalize
the amount of cholesterol intake by the control and STZ-induced diabetic animals
reduced plasma cholesterol levels in STZ-induced diabetic mice, but plasma
cholesterol was still markedly elevated compared with nondiabetic controls. LDL
from STZ-induced diabetic mice was cleared from the plasma and trapped more
rapidly by livers of control mice. STZ treatment reduced liver expression of the
proteoglycan sulfation enzyme, heparan sulfate
N-deacetylase/N-sulfotrasferase-1, an effect that was reproduced in cultured
hepatocytyes by a high glucose-containing medium. CONCLUSIONS: STZ-induced
diabetic, cholesterol-fed mice developed hyperlipidemia due to a non-LDL
receptor defect in clearance of circulating apoB-containing lipoproteins.
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| Investigators with authorship |
| Name | Institution |
| Ira Goldberg | New York University School of Medicine |
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| Genes |
| Symbol | Description |
| Apob | apolipoprotein B |
| Ldlr | low density lipoprotein receptor |
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