GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia.

Impaired insulin action plays a major role in the pathogenesis of type 2 diabetes, a chronic metabolic disorder which imposes a tremendous burden to morbidity and mortality worldwide. Unraveling the molecular mechanisms underlying insulin resistance would improve setting up preventive and treatment...

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Autores principales:	Antonella Marucci, Lazzaro di Mauro, Claudia Menzaghi, Sabrina Prudente, Davide Mangiacotti, Grazia Fini, Giuseppe Lotti, Vincenzo Trischitta, Rosa Di Paola
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/106c7a0720d74e92aec4301aa4230373
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spelling	oai:doaj.org-article:106c7a0720d74e92aec4301aa42303732021-11-18T09:03:35ZGALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia.1932-620310.1371/journal.pone.0070159https://doaj.org/article/106c7a0720d74e92aec4301aa42303732013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894607/?tool=EBIhttps://doaj.org/toc/1932-6203Impaired insulin action plays a major role in the pathogenesis of type 2 diabetes, a chronic metabolic disorder which imposes a tremendous burden to morbidity and mortality worldwide. Unraveling the molecular mechanisms underlying insulin resistance would improve setting up preventive and treatment strategies of type 2 diabetes. Down-regulation of GALNT2, an UDPN-acetyl-alpha-D-galactosamine polypeptideN-acetylgalactosaminyltransferase-2 (ppGalNAc-T2), causes impaired insulin signaling and action in cultured human liver cells. In addition, GALNT2 mRNA levels are down-regulated in liver of spontaneously insulin resistant, diabetic Goto-Kakizaki rats. To investigate the role of GALNT2 in human hyperglycemia, we measured GALNT2 mRNA expression levels in peripheral whole blood cells of 84 non-obese and 46 obese non-diabetic individuals as well as of 98 obese patients with type 2 diabetes. We also measured GALNT2 mRNA expression in human U937 cells cultured under different glucose concentrations. In vivo studies indicated that GALNT2 mRNA levels were significantly reduced from non obese control to obese non diabetic and to obese diabetic individuals (p<0.001). In vitro studies showed that GALNT2 mRNA levels was reduced in U937 cells exposed to high glucose concentrations (i.e. 25 mmol/l glucose) as compared to cells exposed to low glucose concentration (i.e. 5.5 mmol/l glucose +19.5 mmol/l mannitol). In conclusion, our data indicate that GALNT2 is down-regulated in patients with type 2 diabetes and suggest that this association is, at least partly, secondary to hyperglycemia. Further studies are needed to understand whether GALNT2 down-regulation plays a pathogenic role in maintaining and/or aggravating the metabolic abnormalities of diabetic milieu.Antonella MarucciLazzaro di MauroClaudia MenzaghiSabrina PrudenteDavide MangiacottiGrazia FiniGiuseppe LottiVincenzo TrischittaRosa Di PaolaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e70159 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Antonella Marucci Lazzaro di Mauro Claudia Menzaghi Sabrina Prudente Davide Mangiacotti Grazia Fini Giuseppe Lotti Vincenzo Trischitta Rosa Di Paola GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia.
description	Impaired insulin action plays a major role in the pathogenesis of type 2 diabetes, a chronic metabolic disorder which imposes a tremendous burden to morbidity and mortality worldwide. Unraveling the molecular mechanisms underlying insulin resistance would improve setting up preventive and treatment strategies of type 2 diabetes. Down-regulation of GALNT2, an UDPN-acetyl-alpha-D-galactosamine polypeptideN-acetylgalactosaminyltransferase-2 (ppGalNAc-T2), causes impaired insulin signaling and action in cultured human liver cells. In addition, GALNT2 mRNA levels are down-regulated in liver of spontaneously insulin resistant, diabetic Goto-Kakizaki rats. To investigate the role of GALNT2 in human hyperglycemia, we measured GALNT2 mRNA expression levels in peripheral whole blood cells of 84 non-obese and 46 obese non-diabetic individuals as well as of 98 obese patients with type 2 diabetes. We also measured GALNT2 mRNA expression in human U937 cells cultured under different glucose concentrations. In vivo studies indicated that GALNT2 mRNA levels were significantly reduced from non obese control to obese non diabetic and to obese diabetic individuals (p<0.001). In vitro studies showed that GALNT2 mRNA levels was reduced in U937 cells exposed to high glucose concentrations (i.e. 25 mmol/l glucose) as compared to cells exposed to low glucose concentration (i.e. 5.5 mmol/l glucose +19.5 mmol/l mannitol). In conclusion, our data indicate that GALNT2 is down-regulated in patients with type 2 diabetes and suggest that this association is, at least partly, secondary to hyperglycemia. Further studies are needed to understand whether GALNT2 down-regulation plays a pathogenic role in maintaining and/or aggravating the metabolic abnormalities of diabetic milieu.
format	article
author	Antonella Marucci Lazzaro di Mauro Claudia Menzaghi Sabrina Prudente Davide Mangiacotti Grazia Fini Giuseppe Lotti Vincenzo Trischitta Rosa Di Paola
author_facet	Antonella Marucci Lazzaro di Mauro Claudia Menzaghi Sabrina Prudente Davide Mangiacotti Grazia Fini Giuseppe Lotti Vincenzo Trischitta Rosa Di Paola
author_sort	Antonella Marucci
title	GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia.
title_short	GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia.
title_full	GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia.
title_fullStr	GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia.
title_full_unstemmed	GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia.
title_sort	galnt2 expression is reduced in patients with type 2 diabetes: possible role of hyperglycemia.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/106c7a0720d74e92aec4301aa4230373
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GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia.

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