This Article Full Text Full Text (PDF) All Versions of this Article: 146/8/3286    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Iwasaki, T. Articles by Hattori, H. Search for Related Content PubMed PubMed Citation Articles by Iwasaki, T. Articles by Hattori, H.

Deficiency of the Very Low-Density Lipoprotein (VLDL) Receptors in Streptozotocin-Induced Diabetic Rats: Insulin Dependency of the VLDL Receptor

Department of Advanced Medical Technology and Development, BML, Inc. (T.I., T.K., M.I., M. N., H.H.), Kawagoe 50-1101, Japan; Third Department of Internal Medicine, Faculty of Medical Sciences (S.T., Y.Z., J.Su., I. M.), and Second Department of Pathology (H. N.), University of Fukui, Fukui 910-1193, Japan; Department of Cardiovascular Surgery, Hiratsuka Kyosai Hospital (M.T.), Hiratsuka 254-8502, Japan; Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo (J.Sa.), Komaba 153-8904, Japan; Exploratory Research for Advanced Technology of Japan Science and Technology Corp. (J.Sa.), Aomi 135-0064, Japan; Department of Bioscience, Integrated Center for Science, Ehime University (T.F.), Shigenobu 791-0295, Japan; Department of Cardiovascular Biochemistry, St. Barts and the Royal London School of Medicine (N.E.M.), London EC1A 7BE, United Kingdom; and Center for Advanced Genome Research, Institute of Aging, Development, and Cancer, Tohoku University (T.T.Y.), Sendai 981-8555, Japan

Address all correspondence and requests for reprints to: Dr. Sadao Takahashi, Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Matsuoka-cho, Fukui 910-1193, Japan. E-mail: sadaost{at}fmsrsa.fukui-med.ac.jp.

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-rich lipoproteins with high specificity. We examined the etiology of hyperlipidemia in the 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 on d 21 and 28, with a dramatic decline in VLDL-R protein in skeletal muscle (>90%), heart (50%) and a loss of adipose tissues itself on d 28. The reduction of VLDL-R protein in skeletal muscle could not be explained simply by a decrease at the transcriptional level, because a dissociation between VLDL-R protein and mRNA expression was observed. The expression of LDL-R and LDL-R-related protein in liver showed no consistent changes. Furthermore, no effect on VLDL-triglyceride production in liver was observed in STZ rats. A decrease in postheparin plasma lipoprotein lipase activity started on d 7 and continued to d 28 at the 50% level even though severe hyperlipidemia was detected only on d 21 and 28. In rat myoblast cells, serum deprivation for 24 h induced a reduction in VLDL-R proteins. Insulin (10^–6 M), but not IGF-I (10 ng/ml), restored the decreased VLDL-R proteins by serum deprivation. These results suggest that the combination of VLDL-R deficiency and reduced plasma lipoprotein lipase activity may be responsible for severe hyperlipidemia in insulin-deficient diabetes.

This article has been cited by other articles:

				D. An and B. Rodrigues Role of changes in cardiac metabolism in development of diabetic cardiomyopathy Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1489 - H1506. [Abstract] [Full Text] [PDF]

				T. Shinohara, N. Takahashi, T. Ooie, M. Hara, S. Shigematsu, M. Nakagawa, H. Yonemochi, T. Saikawa, and H. Yoshimatsu Phosphatidylinositol 3-kinase-dependent activation of akt, an essential signal for hyperthermia-induced heat-shock protein 72, is attenuated in streptozotocin-induced diabetic heart. Diabetes, May 1, 2006; 55(5): 1307 - 1315. [Abstract] [Full Text] [PDF]