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

• Published in: Endocrinology (Philadelphia) 2005-08, Vol.146 (8), p.3286-3294
• Main Authors: Iwasaki, Tadao, Takahashi, Sadao, Takahashi, Masao, Zenimaru, Yasuo, Kujiraoka, Takeshi, Ishihara, Mitsuaki, Nagano, Makoto, Suzuki, Jinya, Miyamori, Isamu, Naiki, Hironobu, Sakai, Juro, Fujino, Takahiro, Miller, Norman E, Yamamoto, Tokuo T, Hattori, Hiroaki
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - physiopathology; Animals; Biological and medical sciences; Cardiac muscle; Cardiovascular diseases; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Cholesterol, VLDL - blood; Density; Deprivation; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gene expression; Heart - physiopathology; Hyperlipidemia; Hyperlipidemias - etiology; Insulin; Insulin - physiology; Insulin-like growth factor I; Lipase; Lipoprotein lipase; Lipoproteins; Lipoproteins (very low density); Lipoproteins - metabolism; Liver; Low density lipoprotein; Low density lipoprotein receptors; Male; Medical sciences; Muscle, Skeletal - physiopathology; Muscles; Musculoskeletal system; Myoblasts; Proteins; Rats; Rats, Sprague-Dawley; Receptor density; Receptors; Receptors, LDL - deficiency; Receptors, LDL - genetics; Receptors, LDL - physiology; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; RNA - genetics; RNA - isolation & purification; Skeletal muscle; Streptozocin; Triglycerides; Triglycerides - metabolism
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2005-0043

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.