Deficiency of the very low-density lipoprotein (VLDL) receptors in streptozotocin-induced diabetic rats: insulin dependency of the VLDL receptor.
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 (approximately 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.
Iwasaki
Tadao
T
Department of Advanced Medical Technology and Development, BML, Inc, Kawagoe, Japan.
Takahashi
Sadao
S
Takahashi
Masao
M
Zenimaru
Yasuo
Y
Kujiraoka
Takeshi
T
Ishihara
Mitsuaki
M
Nagano
Makoto
M
Suzuki
Jinya
J
Miyamori
Isamu
I
Naiki
Hironobu
H
Sakai
Juro
J
Fujino
Takahiro
T
Miller
Norman E
NE
Yamamoto
Tokuo T
TT
Hattori
Hiroaki
H
D000273:Adipose Tissue / Q000503:physiopathology; D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology; D006949:Hyperlipidemias / Q000209:etiology; D007328:Insulin / Q000502:physiology*; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000503:physiopathology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D007328:Insulin; D008074:Lipoproteins; D011973:Receptors, LDL; D014280:Triglycerides; C036053:VLDL receptor; D012313:RNA