Deficiency of the very low-density lipoprotein (VLDL) receptors in streptozotocin-induced diabetic rats: Insulin dependency of the VLDL receptor

Tadao Iwasaki, Sadao Takahashi, Masao Takahashi, Yasuo Zenimaru, Takeshi Kujiraoka, Mitsuaki Ishihara, Makoto Nagano, Jinya Suzuki, Isamu Miyamori, Hironobu Naiki, Juro Sakai, Takahiro Fujino, Norman E. Miller, Tokuo Yamamoto, Hiroaki Hattori

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)3286-3294
Number of pages9
JournalEndocrinology
Volume146
Issue number8
DOIs
Publication statusPublished - 2005 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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