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Article: Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice
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TitleAngiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice
 
AuthorsXu, A1
Lam, MC1
Chan, KW1
Wang, Y1
Zhang, J1
Boo, RLC1
Xu, JY1
Chen, B1
Chow, WS1
Tso, AWK1
Lam, KSL1
 
KeywordsAdipokine
Diabetes
Fatty liver
Metabolism
 
Issue Date2005
 
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
 
CitationProceedings Of The National Academy Of Sciences Of The United States Of America, 2005, v. 102 n. 17, p. 6086-6091 [How to Cite?]
DOI: http://dx.doi.org/10.1073/pnas.0408452102
 
AbstractAngiopoietin-like protein 4 (ANGPTL4) is a circulating protein predominantly expressed in adipose tissue and liver. Several recent studies demonstrated that ANGPTL4 is the target gene of peroxisome proliferation activators, the agonists of which are widely used as the antidiabetic and lipid-lowering drugs. Here we provide evidence that ANGPTL4 is a blood-borne hormone directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. Adenovirus-mediated expression of ANGPTL4 potently decreased blood glucose and improved glucose tolerance, whereas it induced hyperlipidemia, fatty liver, and hepatomegaly in C57 mice. In db/db diabetic mice, ANGPTL4 treatment reduced hyperglycemia to a normal level, and markedly alleviated glucose intolerance and hyperinsulinemia. Ex vivo studies on primary rat hepatocytes revealed that ANGPTL4 significantly decreased hepatic glucose production and enhanced insulin-mediated inhibition of gluconeogenesis. Serum levels of ANGPTL4 in human subjects inversely correlated with plasma glucose concentrations and HOMA IR, the homeostasis model assessment of insulin resistance. In patients with type 2 diabetes, serum levels of ANGPTL4 were significantly lower than those in healthy subjects, suggesting that the decreased ANGPTL4 could be a causative factor of this disease. These results collectively indicate that ANGPTL4 exerts distinct effects on glucose and lipid metabolism, and that its beneficial effect on glucose homeostasis might be useful for the treatment of diabetes. © 2005 by The National Academy of Sciences of the USA.
 
ISSN0027-8424
2013 Impact Factor: 9.809
 
DOIhttp://dx.doi.org/10.1073/pnas.0408452102
 
PubMed Central IDPMC1087912
 
ISI Accession Number IDWOS:000228738800036
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorXu, A
 
dc.contributor.authorLam, MC
 
dc.contributor.authorChan, KW
 
dc.contributor.authorWang, Y
 
dc.contributor.authorZhang, J
 
dc.contributor.authorBoo, RLC
 
dc.contributor.authorXu, JY
 
dc.contributor.authorChen, B
 
dc.contributor.authorChow, WS
 
dc.contributor.authorTso, AWK
 
dc.contributor.authorLam, KSL
 
dc.date.accessioned2008-06-12T06:35:15Z
 
dc.date.available2008-06-12T06:35:15Z
 
dc.date.issued2005
 
dc.description.abstractAngiopoietin-like protein 4 (ANGPTL4) is a circulating protein predominantly expressed in adipose tissue and liver. Several recent studies demonstrated that ANGPTL4 is the target gene of peroxisome proliferation activators, the agonists of which are widely used as the antidiabetic and lipid-lowering drugs. Here we provide evidence that ANGPTL4 is a blood-borne hormone directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. Adenovirus-mediated expression of ANGPTL4 potently decreased blood glucose and improved glucose tolerance, whereas it induced hyperlipidemia, fatty liver, and hepatomegaly in C57 mice. In db/db diabetic mice, ANGPTL4 treatment reduced hyperglycemia to a normal level, and markedly alleviated glucose intolerance and hyperinsulinemia. Ex vivo studies on primary rat hepatocytes revealed that ANGPTL4 significantly decreased hepatic glucose production and enhanced insulin-mediated inhibition of gluconeogenesis. Serum levels of ANGPTL4 in human subjects inversely correlated with plasma glucose concentrations and HOMA IR, the homeostasis model assessment of insulin resistance. In patients with type 2 diabetes, serum levels of ANGPTL4 were significantly lower than those in healthy subjects, suggesting that the decreased ANGPTL4 could be a causative factor of this disease. These results collectively indicate that ANGPTL4 exerts distinct effects on glucose and lipid metabolism, and that its beneficial effect on glucose homeostasis might be useful for the treatment of diabetes. © 2005 by The National Academy of Sciences of the USA.
 
dc.description.naturepublished_or_final_version
 
dc.format.extent388 bytes
 
dc.format.mimetypetext/html
 
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2005, v. 102 n. 17, p. 6086-6091 [How to Cite?]
DOI: http://dx.doi.org/10.1073/pnas.0408452102
 
dc.identifier.doihttp://dx.doi.org/10.1073/pnas.0408452102
 
dc.identifier.epage6091
 
dc.identifier.hkuros98180
 
dc.identifier.hkuros120053
 
dc.identifier.isiWOS:000228738800036
 
dc.identifier.issn0027-8424
2013 Impact Factor: 9.809
 
dc.identifier.issue17
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC1087912
 
dc.identifier.pmid15837923
 
dc.identifier.scopuseid_2-s2.0-20944447890
 
dc.identifier.spage6086
 
dc.identifier.urihttp://hdl.handle.net/10722/49139
 
dc.identifier.volume102
 
dc.languageeng
 
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
 
dc.relation.referencesReferences in Scopus
 
dc.rightsNational Academy of Sciences Proceedings. Copyright © National Academy of Sciences.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subjectAdipokine
 
dc.subjectDiabetes
 
dc.subjectFatty liver
 
dc.subjectMetabolism
 
dc.titleAngiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong