File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice

TitleAngiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice
Authors
KeywordsAdipokine
Diabetes
Fatty liver
Metabolism
Issue Date2005
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2005, v. 102 n. 17, p. 6086-6091 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/49139
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXu, Aen_HK
dc.contributor.authorLam, MCen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorZhang, Jen_HK
dc.contributor.authorBoo, RLCen_HK
dc.contributor.authorXu, JYen_HK
dc.contributor.authorChen, Ben_HK
dc.contributor.authorChow, WSen_HK
dc.contributor.authorTso, AWKen_HK
dc.contributor.authorLam, KSLen_HK
dc.date.accessioned2008-06-12T06:35:15Z-
dc.date.available2008-06-12T06:35:15Z-
dc.date.issued2005en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2005, v. 102 n. 17, p. 6086-6091en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49139-
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.en_HK
dc.format.extent388 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.rightsNational Academy of Sciences Proceedings. Copyright © National Academy of Sciences.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectAdipokineen_HK
dc.subjectDiabetesen_HK
dc.subjectFatty liveren_HK
dc.subjectMetabolismen_HK
dc.titleAngiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=102&issue=17&spage=6086&epage=6091&date=2005&atitle=Angiopoietin-like+protein+4+decreases+blood+glucose+and+improves+glucose+tolerance+but+induces+hyperlipidemia+and+hepatic+steatosis+in+miceen_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.emailTso, AWK: awk.tso@gmail.comen_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.identifier.authorityTso, AWK=rp00535en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1073/pnas.0408452102en_HK
dc.identifier.pmid15837923-
dc.identifier.pmcidPMC1087912en_HK
dc.identifier.scopuseid_2-s2.0-20944447890en_HK
dc.identifier.hkuros98180-
dc.identifier.hkuros120053-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-20944447890&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume102en_HK
dc.identifier.issue17en_HK
dc.identifier.spage6086en_HK
dc.identifier.epage6091en_HK
dc.identifier.isiWOS:000228738800036-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridLam, MC=36879143100en_HK
dc.identifier.scopusauthoridChan, KW=55041332800en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK
dc.identifier.scopusauthoridZhang, J=35504391800en_HK
dc.identifier.scopusauthoridBoo, RLC=8508989500en_HK
dc.identifier.scopusauthoridXu, JY=8947805200en_HK
dc.identifier.scopusauthoridChen, B=8836680100en_HK
dc.identifier.scopusauthoridChow, WS=7402281153en_HK
dc.identifier.scopusauthoridTso, AWK=6701371436en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats