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Article: The adaptor protein APPL2 inhibits insulin-stimulated glucose uptake by interacting with TBC1D1 in skeletal muscle

TitleThe adaptor protein APPL2 inhibits insulin-stimulated glucose uptake by interacting with TBC1D1 in skeletal muscle
Authors
Issue Date2014
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
Diabetes, 2014, v. 63 n. 11, p. 3748-3758 How to Cite?
AbstractInsulin stimulates glucose uptake by promoting the trafficking of GLUT4 to the plasma membrane in muscle cells, and impairment of this insulin action contributes to hyperglycemia in type 2 diabetes. The adaptor protein APPL1 potentiates insulin-stimulated Akt activation and downstream actions. However, the physiological functions of APPL2, a close homolog of APPL1, in regulating glucose metabolism remain elusive. We show that insulin-evoked plasma membrane recruitment of GLUT4 and glucose uptake are impaired by APPL2 overexpression but enhanced by APPL2 knockdown. Likewise, conditional deletion of APPL2 in skeletal muscles enhances insulin sensitivity, leading to an improvement in glucose tolerance. We identified the Rab-GTPase–activating protein TBC1D1 as an interacting partner of APPL2. Insulin stimulates TBC1D1 phosphorylation on serine 235, leading to enhanced interaction with the BAR domain of APPL2, which in turn suppresses insulin-evoked TBC1D1 phosphorylation on threonine 596 in cultured myotubes and skeletal muscle. Substitution of serine 235 with alanine diminishes APPL2-mediated inhibition on insulin-dependent TBC1D1 phosphorylation on threonine 596 and the suppressive effects of TBC1D1 on insulin-induced glucose uptake and GLUT4 translocation to the plasma membrane in cultured myotubes. Therefore, the APPL2–TBC1D1 interaction is a key step to fine tune insulin-stimulated glucose uptake by regulating the membrane recruitment of GLUT4 in skeletal muscle.
Persistent Identifierhttp://hdl.handle.net/10722/199141
ISSN
2019 Impact Factor: 7.72
2015 SCImago Journal Rankings: 5.185
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheng, KYen_US
dc.contributor.authorZhu, Wen_US
dc.contributor.authorChen, Ben_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorWu, Den_US
dc.contributor.authorSweeney, Gen_US
dc.contributor.authorWang, Ben_US
dc.contributor.authorLam, KSLen_US
dc.contributor.authorXu, Aen_US
dc.date.accessioned2014-07-22T01:04:54Z-
dc.date.available2014-07-22T01:04:54Z-
dc.date.issued2014en_US
dc.identifier.citationDiabetes, 2014, v. 63 n. 11, p. 3748-3758en_US
dc.identifier.issn0012-1797-
dc.identifier.urihttp://hdl.handle.net/10722/199141-
dc.description.abstractInsulin stimulates glucose uptake by promoting the trafficking of GLUT4 to the plasma membrane in muscle cells, and impairment of this insulin action contributes to hyperglycemia in type 2 diabetes. The adaptor protein APPL1 potentiates insulin-stimulated Akt activation and downstream actions. However, the physiological functions of APPL2, a close homolog of APPL1, in regulating glucose metabolism remain elusive. We show that insulin-evoked plasma membrane recruitment of GLUT4 and glucose uptake are impaired by APPL2 overexpression but enhanced by APPL2 knockdown. Likewise, conditional deletion of APPL2 in skeletal muscles enhances insulin sensitivity, leading to an improvement in glucose tolerance. We identified the Rab-GTPase–activating protein TBC1D1 as an interacting partner of APPL2. Insulin stimulates TBC1D1 phosphorylation on serine 235, leading to enhanced interaction with the BAR domain of APPL2, which in turn suppresses insulin-evoked TBC1D1 phosphorylation on threonine 596 in cultured myotubes and skeletal muscle. Substitution of serine 235 with alanine diminishes APPL2-mediated inhibition on insulin-dependent TBC1D1 phosphorylation on threonine 596 and the suppressive effects of TBC1D1 on insulin-induced glucose uptake and GLUT4 translocation to the plasma membrane in cultured myotubes. Therefore, the APPL2–TBC1D1 interaction is a key step to fine tune insulin-stimulated glucose uptake by regulating the membrane recruitment of GLUT4 in skeletal muscle.-
dc.languageengen_US
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/-
dc.relation.ispartofDiabetesen_US
dc.titleThe adaptor protein APPL2 inhibits insulin-stimulated glucose uptake by interacting with TBC1D1 in skeletal muscleen_US
dc.typeArticleen_US
dc.identifier.emailCheng, KY: dorncky@hkucc.hku.hken_US
dc.identifier.emailZhu, W: pylonzhu@hku.hken_US
dc.identifier.emailWang, Y: yuwanghk@hku.hken_US
dc.identifier.emailLam, KSL: ksllam@hku.hken_US
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_US
dc.identifier.authorityCheng, KY=rp01672en_US
dc.identifier.authorityWang, Y=rp00239en_US
dc.identifier.authorityLam, KSL=rp00343en_US
dc.identifier.authorityXu, A=rp00485en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.2337/db14-0337-
dc.identifier.pmid24879834-
dc.identifier.scopuseid_2-s2.0-84908657614-
dc.identifier.hkuros230293en_US
dc.identifier.volume63en_US
dc.identifier.issue11-
dc.identifier.spage3748en_US
dc.identifier.epage3758en_US
dc.identifier.eissn1939-327X-
dc.identifier.isiWOS:000343966100024-
dc.publisher.placeUnited States-
dc.identifier.issnl0012-1797-

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