Cargando…

Changes in Glycogen and Glycosaminoglycan Levels in Hepatocytes of Iduronate-2-Sulfatase Knockout Mice before and after Recombinant Iduronate-2-Sulfatase Supplementation

PURPOSE: Mucopolysaccharidosis II (MPS II) is a lysosomal storage disorder caused by a deficiency of iduronate-2 sulfatase (IdS), which is involved in the degradation of glycosaminoglycan (GAG). In this study, the frequency of fasting hypoglycemia in patients with MPS II was investigated and changes...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Jee Hyun, Choe, Yon Ho, Kim, Su Jin, Paik, Kyung Hoon, Jin, Dong-Kyu
Formato: Texto
Lenguaje:English
Publicado: Yonsei University College of Medicine 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3051226/
https://www.ncbi.nlm.nih.gov/pubmed/21319344
http://dx.doi.org/10.3349/ymj.2011.52.2.263
_version_ 1782199458744762368
author Lee, Jee Hyun
Choe, Yon Ho
Kim, Su Jin
Paik, Kyung Hoon
Jin, Dong-Kyu
author_facet Lee, Jee Hyun
Choe, Yon Ho
Kim, Su Jin
Paik, Kyung Hoon
Jin, Dong-Kyu
author_sort Lee, Jee Hyun
collection PubMed
description PURPOSE: Mucopolysaccharidosis II (MPS II) is a lysosomal storage disorder caused by a deficiency of iduronate-2 sulfatase (IdS), which is involved in the degradation of glycosaminoglycan (GAG). In this study, the frequency of fasting hypoglycemia in patients with MPS II was investigated and changes in accumulation of glycogen and GAG in the hepatocytes of IdS-knockout (KO) mice were evaluated before and after recombinant IdS enzyme replacement therapy (ERT). MATERIALS AND METHODS: Plasma glucose levels were evaluated after an 8-hour fast in 50 patients with MPS II. The IdS-KO mice were divided into three groups (group 2; saline, group 3; 0.15 mg/kg of IdS, and group 4; 0.5 mg/kg of IdS); wild-type mice were included as controls (group 1). ERT was initiated intravenously at four weeks of age, and continued every week until 20 weeks of age. RESULTS: The mean glucose level after an 8-hour fast was 94.1 ± 23.7 mg/dL in the patients with MPS II. Two (4%) out of 50 patients had fasting hypoglycemia. For the mice, GAG in the lysosomes nearly disappeared and glycogen particles in the cytoplasm were restored to the normal range in group 4. CONCLUSION: Glucose metabolism in patients with MPS II appeared to function well despite hepatocytic GAG accumulation and hypothetical glycogen depletion. A higher dose of IdS infusion in MPS II mice led to disappearance of lysosomal GAG and restoration of glycogen to the cytoplasm of hepatocytes.
format Text
id pubmed-3051226
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Yonsei University College of Medicine
record_format MEDLINE/PubMed
spelling pubmed-30512262011-03-09 Changes in Glycogen and Glycosaminoglycan Levels in Hepatocytes of Iduronate-2-Sulfatase Knockout Mice before and after Recombinant Iduronate-2-Sulfatase Supplementation Lee, Jee Hyun Choe, Yon Ho Kim, Su Jin Paik, Kyung Hoon Jin, Dong-Kyu Yonsei Med J Original Article PURPOSE: Mucopolysaccharidosis II (MPS II) is a lysosomal storage disorder caused by a deficiency of iduronate-2 sulfatase (IdS), which is involved in the degradation of glycosaminoglycan (GAG). In this study, the frequency of fasting hypoglycemia in patients with MPS II was investigated and changes in accumulation of glycogen and GAG in the hepatocytes of IdS-knockout (KO) mice were evaluated before and after recombinant IdS enzyme replacement therapy (ERT). MATERIALS AND METHODS: Plasma glucose levels were evaluated after an 8-hour fast in 50 patients with MPS II. The IdS-KO mice were divided into three groups (group 2; saline, group 3; 0.15 mg/kg of IdS, and group 4; 0.5 mg/kg of IdS); wild-type mice were included as controls (group 1). ERT was initiated intravenously at four weeks of age, and continued every week until 20 weeks of age. RESULTS: The mean glucose level after an 8-hour fast was 94.1 ± 23.7 mg/dL in the patients with MPS II. Two (4%) out of 50 patients had fasting hypoglycemia. For the mice, GAG in the lysosomes nearly disappeared and glycogen particles in the cytoplasm were restored to the normal range in group 4. CONCLUSION: Glucose metabolism in patients with MPS II appeared to function well despite hepatocytic GAG accumulation and hypothetical glycogen depletion. A higher dose of IdS infusion in MPS II mice led to disappearance of lysosomal GAG and restoration of glycogen to the cytoplasm of hepatocytes. Yonsei University College of Medicine 2011-03-01 2011-01-29 /pmc/articles/PMC3051226/ /pubmed/21319344 http://dx.doi.org/10.3349/ymj.2011.52.2.263 Text en © Copyright: Yonsei University College of Medicine 2011 http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Lee, Jee Hyun
Choe, Yon Ho
Kim, Su Jin
Paik, Kyung Hoon
Jin, Dong-Kyu
Changes in Glycogen and Glycosaminoglycan Levels in Hepatocytes of Iduronate-2-Sulfatase Knockout Mice before and after Recombinant Iduronate-2-Sulfatase Supplementation
title Changes in Glycogen and Glycosaminoglycan Levels in Hepatocytes of Iduronate-2-Sulfatase Knockout Mice before and after Recombinant Iduronate-2-Sulfatase Supplementation
title_full Changes in Glycogen and Glycosaminoglycan Levels in Hepatocytes of Iduronate-2-Sulfatase Knockout Mice before and after Recombinant Iduronate-2-Sulfatase Supplementation
title_fullStr Changes in Glycogen and Glycosaminoglycan Levels in Hepatocytes of Iduronate-2-Sulfatase Knockout Mice before and after Recombinant Iduronate-2-Sulfatase Supplementation
title_full_unstemmed Changes in Glycogen and Glycosaminoglycan Levels in Hepatocytes of Iduronate-2-Sulfatase Knockout Mice before and after Recombinant Iduronate-2-Sulfatase Supplementation
title_short Changes in Glycogen and Glycosaminoglycan Levels in Hepatocytes of Iduronate-2-Sulfatase Knockout Mice before and after Recombinant Iduronate-2-Sulfatase Supplementation
title_sort changes in glycogen and glycosaminoglycan levels in hepatocytes of iduronate-2-sulfatase knockout mice before and after recombinant iduronate-2-sulfatase supplementation
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3051226/
https://www.ncbi.nlm.nih.gov/pubmed/21319344
http://dx.doi.org/10.3349/ymj.2011.52.2.263
work_keys_str_mv AT leejeehyun changesinglycogenandglycosaminoglycanlevelsinhepatocytesofiduronate2sulfataseknockoutmicebeforeandafterrecombinantiduronate2sulfatasesupplementation
AT choeyonho changesinglycogenandglycosaminoglycanlevelsinhepatocytesofiduronate2sulfataseknockoutmicebeforeandafterrecombinantiduronate2sulfatasesupplementation
AT kimsujin changesinglycogenandglycosaminoglycanlevelsinhepatocytesofiduronate2sulfataseknockoutmicebeforeandafterrecombinantiduronate2sulfatasesupplementation
AT paikkyunghoon changesinglycogenandglycosaminoglycanlevelsinhepatocytesofiduronate2sulfataseknockoutmicebeforeandafterrecombinantiduronate2sulfatasesupplementation
AT jindongkyu changesinglycogenandglycosaminoglycanlevelsinhepatocytesofiduronate2sulfataseknockoutmicebeforeandafterrecombinantiduronate2sulfatasesupplementation