2003 Fiscal Year Final Research Report Summary
Elucidation of etiology in diabetic dyslipidemia and VLDL receptor expression
| Project/Area Number |
14571087
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Faculty of Medical Sciences, University of Fukui |
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Principal Investigator |
TAKAHASHI Sadao TAKAHASHI,Sadao, 医学部附属病院, 講師 (50303376)
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| Co-Investigator(Kenkyū-buntansha) |
HATTORI Hiroaki BML Inc, Chief Investigator, 代謝調節研究課, 主席研究員
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| Project Period (FY) |
2002 – 2003
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| Keywords | VLDL receptor / diabetes mellitus / hyperlipidemia / lipoprotein lipase / insulin deficiency / knockout mice / diabetic model animal / gene regulation |
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| Research Abstract |
Hyperlipidemia is a common feature of diabetes and is related to cardiovascular disease.The very low-density lipoprotein receptor(VLDL-R) is a member of the low-density lipoprotein receptor(LDL-R) family.It binds and internalizes triglyceride(TG)-rich lipoproteins with high specificity.We examined the etiology of hyperlipidemia in insulin deficient state.VLDL-R expression in heart and skeletal muscle were measured in rats with streptozotocin(STZ)-induced diabetes. STZ rats showed severe hyperlipidemia with a dramatic decline in VLDL-R protein in skeletal muscle (>90%), heart(about 50%) and a loss of adipose tissues itself on day 28.The reduction of VLDL-R protein in skeletal muscle could not be explained by a decrease at transcriptional level, as VLDL-R mRNA was reduced by only about 25%.The expression of the LDL receptor and LDL receptor-related protein(LRP-1) in liver showed no consistent changes.Furthermore, no effect on VLDL-TG production in liver was observed in STZ rats, whereas post-heparin plasma lipoprotein lipase(LPL)activity was reduced.In rat myotuble cells, insulin (10^<-6>M) or IGF-1 (10 ng/ml)recovered the decreased VLDL receptor proteins. These results suggest that both VLDL-R deficiency and reduced plasma LPL activity contribute to hyperlipidemia in insulin-deficient diabetes.
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Research Products
(4 results)
