Ongoing insulin therapy maintains LDL receptors at highly expressed state in Type-1 diabetic people;yet Type-1 diabetics are liable of having higher plasma LDL level. This disparity has raised doubt on the probability...Ongoing insulin therapy maintains LDL receptors at highly expressed state in Type-1 diabetic people;yet Type-1 diabetics are liable of having higher plasma LDL level. This disparity has raised doubt on the probability of existence of functionally active LDL receptor in such people. Confocal microscopy and immunoprecipitation have made it evident that a portion of insulin and LDL receptors remain together in a co-localized mode, which only gets freed in presence of insulin. The findings of this study have shown that insulin therapy protects Type-1 diabetic people from the pathogenesis of atherosclerosis by decimating the inactivity of the co-localized LDL receptors in addition to its regular effect of having increased glucose tolerance. The existence of co-localized state of these two receptors and their dependence on insulin for independent activity has, at least, presented a reason for developing hypercholesterolemia and advanced coronary atherosclerotic lesion in chronic Type-1 diabetic subjects.展开更多
Low density lipoprotein (LDL) receptor is a cell surface glycoprotein that regulates plasma cholesterol by mediating endocytosis of LDL and supplies cells with cholesterol. LDL receptor was first identified in 1973 by...Low density lipoprotein (LDL) receptor is a cell surface glycoprotein that regulates plasma cholesterol by mediating endocytosis of LDL and supplies cells with cholesterol. LDL receptor was first identified in 1973 by Goldstein and Brown, who won the Nobel Prize in 1985. Mutations in the LDL receptor gene cause familial hyper-cholesterolemia (FH), a common disease that affects about 1 in 500 people in most populations. Individuals heterozygous for LDL receptor mutation in one allele express half the normal number of functional receptors on their cell surface. This produces a two-fold elevation in plasma LDL-cholesterol concentration. The excess plasma LDL-cholesterol deposits in tendons and arterial walls, forming tendon xanthomas and atherosclerotic plaques. The rare FH homozygotes (about 1 per million people) have mutations in both LDL receptor genes, express few or no functional LDL receptors on their cell surfaces. Their plasma LDL-cholesterol level rises dramatically and displays a pathognomonic sk展开更多
We previously reported that Dai-saiko-to (Da-Chai-Hu-Tang), a traditional Japanese kampo medicine, increased LDL receptor mRNA expression in the liver of the hypercholesterolemic rabbits. In this study, we focused on ...We previously reported that Dai-saiko-to (Da-Chai-Hu-Tang), a traditional Japanese kampo medicine, increased LDL receptor mRNA expression in the liver of the hypercholesterolemic rabbits. In this study, we focused on LDL receptor gene expression in a human hepatoma cell line (HepG2) treated with Dai-saiko-to extract and the extracts of eight herbs presented in Dai-saiko-to. Dai-saiko-to extract significantly increased LDL receptor gene and SREBP2 gene expression compared with the control. The extracts of four herbs, Bupleurum root, Pinellia tuber, Scutellaria root and Peony root significantly increased the LDL receptor gene expression. Whereas, Jujube, Immature orange, Ginger and Rhubarb extracts did not change the gene expression. These results suggest that Dai-saiko-to increased the expression of the cholesterol transport gene (LDL receptor) regulated by SREBP2 gene in the human hepatoma cell line. The pharmacological activity of Dai-saiko-to against hypercholesterolemia and atheromatous lesions related for these four herbal components.展开更多
文摘Ongoing insulin therapy maintains LDL receptors at highly expressed state in Type-1 diabetic people;yet Type-1 diabetics are liable of having higher plasma LDL level. This disparity has raised doubt on the probability of existence of functionally active LDL receptor in such people. Confocal microscopy and immunoprecipitation have made it evident that a portion of insulin and LDL receptors remain together in a co-localized mode, which only gets freed in presence of insulin. The findings of this study have shown that insulin therapy protects Type-1 diabetic people from the pathogenesis of atherosclerosis by decimating the inactivity of the co-localized LDL receptors in addition to its regular effect of having increased glucose tolerance. The existence of co-localized state of these two receptors and their dependence on insulin for independent activity has, at least, presented a reason for developing hypercholesterolemia and advanced coronary atherosclerotic lesion in chronic Type-1 diabetic subjects.
文摘Low density lipoprotein (LDL) receptor is a cell surface glycoprotein that regulates plasma cholesterol by mediating endocytosis of LDL and supplies cells with cholesterol. LDL receptor was first identified in 1973 by Goldstein and Brown, who won the Nobel Prize in 1985. Mutations in the LDL receptor gene cause familial hyper-cholesterolemia (FH), a common disease that affects about 1 in 500 people in most populations. Individuals heterozygous for LDL receptor mutation in one allele express half the normal number of functional receptors on their cell surface. This produces a two-fold elevation in plasma LDL-cholesterol concentration. The excess plasma LDL-cholesterol deposits in tendons and arterial walls, forming tendon xanthomas and atherosclerotic plaques. The rare FH homozygotes (about 1 per million people) have mutations in both LDL receptor genes, express few or no functional LDL receptors on their cell surfaces. Their plasma LDL-cholesterol level rises dramatically and displays a pathognomonic sk
文摘We previously reported that Dai-saiko-to (Da-Chai-Hu-Tang), a traditional Japanese kampo medicine, increased LDL receptor mRNA expression in the liver of the hypercholesterolemic rabbits. In this study, we focused on LDL receptor gene expression in a human hepatoma cell line (HepG2) treated with Dai-saiko-to extract and the extracts of eight herbs presented in Dai-saiko-to. Dai-saiko-to extract significantly increased LDL receptor gene and SREBP2 gene expression compared with the control. The extracts of four herbs, Bupleurum root, Pinellia tuber, Scutellaria root and Peony root significantly increased the LDL receptor gene expression. Whereas, Jujube, Immature orange, Ginger and Rhubarb extracts did not change the gene expression. These results suggest that Dai-saiko-to increased the expression of the cholesterol transport gene (LDL receptor) regulated by SREBP2 gene in the human hepatoma cell line. The pharmacological activity of Dai-saiko-to against hypercholesterolemia and atheromatous lesions related for these four herbal components.
