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Role of glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes
In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends on insulin action. The transport of LPL to endothelial cells and its enzymatic activity are maintained by the formation of lipolyt...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512915/ https://www.ncbi.nlm.nih.gov/pubmed/37448184 http://dx.doi.org/10.1111/jdi.14056 |
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author | Kurooka, Naoko Eguchi, Jun Wada, Jun |
author_facet | Kurooka, Naoko Eguchi, Jun Wada, Jun |
author_sort | Kurooka, Naoko |
collection | PubMed |
description | In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends on insulin action. The transport of LPL to endothelial cells and its enzymatic activity are maintained by the formation of lipolytic complex depending on the multiple positive (glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 [GPIHBP1], apolipoprotein C‐II [APOC2], APOA5, heparan sulfate proteoglycan [HSPG], lipase maturation factor 1 [LFM1] and sel‐1 suppressor of lin‐12‐like [SEL1L]) and negative regulators (APOC1, APOC3, angiopoietin‐like proteins [ANGPTL]3, ANGPTL4 and ANGPTL8). Among the regulators, GPIHBP1 is a crucial molecule for the translocation of LPL from parenchymal cells to the luminal surface of capillary endothelial cells, and maintenance of lipolytic activity; that is, hydrolyzation of triglyceride into free fatty acids and monoglyceride, and conversion from chylomicron to chylomicron remnant in the exogenous pathway and from very low‐density lipoprotein to low‐density lipoprotein in the endogenous pathway. The null mutation of GPIHBP1 causes severe hypertriglyceridemia and pancreatitis, and GPIGBP1 autoantibody syndrome also causes severe hypertriglyceridemia and recurrent episodes of acute pancreatitis. In patients with type 2 diabetes, the elevated serum triglyceride levels negatively correlate with circulating LPL levels, and positively with circulating APOC1, APOC3, ANGPTL3, ANGPTL4 and ANGPTL8 levels. In contrast, circulating GPIHBP1 levels are not altered in type 2 diabetes patients with higher serum triglyceride levels, whereas they are elevated in type 2 diabetes patients with diabetic retinopathy and nephropathy. The circulating regulators of lipolytic complex might be new biomarkers for lipid and glucose metabolism, and diabetic vascular complications. |
format | Online Article Text |
id | pubmed-10512915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105129152023-09-22 Role of glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes Kurooka, Naoko Eguchi, Jun Wada, Jun J Diabetes Investig Review Article In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends on insulin action. The transport of LPL to endothelial cells and its enzymatic activity are maintained by the formation of lipolytic complex depending on the multiple positive (glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 [GPIHBP1], apolipoprotein C‐II [APOC2], APOA5, heparan sulfate proteoglycan [HSPG], lipase maturation factor 1 [LFM1] and sel‐1 suppressor of lin‐12‐like [SEL1L]) and negative regulators (APOC1, APOC3, angiopoietin‐like proteins [ANGPTL]3, ANGPTL4 and ANGPTL8). Among the regulators, GPIHBP1 is a crucial molecule for the translocation of LPL from parenchymal cells to the luminal surface of capillary endothelial cells, and maintenance of lipolytic activity; that is, hydrolyzation of triglyceride into free fatty acids and monoglyceride, and conversion from chylomicron to chylomicron remnant in the exogenous pathway and from very low‐density lipoprotein to low‐density lipoprotein in the endogenous pathway. The null mutation of GPIHBP1 causes severe hypertriglyceridemia and pancreatitis, and GPIGBP1 autoantibody syndrome also causes severe hypertriglyceridemia and recurrent episodes of acute pancreatitis. In patients with type 2 diabetes, the elevated serum triglyceride levels negatively correlate with circulating LPL levels, and positively with circulating APOC1, APOC3, ANGPTL3, ANGPTL4 and ANGPTL8 levels. In contrast, circulating GPIHBP1 levels are not altered in type 2 diabetes patients with higher serum triglyceride levels, whereas they are elevated in type 2 diabetes patients with diabetic retinopathy and nephropathy. The circulating regulators of lipolytic complex might be new biomarkers for lipid and glucose metabolism, and diabetic vascular complications. John Wiley and Sons Inc. 2023-07-13 /pmc/articles/PMC10512915/ /pubmed/37448184 http://dx.doi.org/10.1111/jdi.14056 Text en © 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Kurooka, Naoko Eguchi, Jun Wada, Jun Role of glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes |
title | Role of glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes |
title_full | Role of glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes |
title_fullStr | Role of glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes |
title_full_unstemmed | Role of glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes |
title_short | Role of glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes |
title_sort | role of glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512915/ https://www.ncbi.nlm.nih.gov/pubmed/37448184 http://dx.doi.org/10.1111/jdi.14056 |
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