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Title of Journal: Cell Mol Life Sci

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Abbravation: Cellular and Molecular Life Sciences

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Springer Basel

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DOI

10.1016/0264-9993(86)90003-9

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1420-9071

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Apolipoprotein CIII hyperactivates β cell CaSubsc

Authors: Yue Shi Guang Yang Jia Yu Lina Yu Ruth Westenbroek William A Catterall Lisa JunttiBerggren PerOlof Berggren ShaoNian Yang
Publish Date: 2013/08/15
Volume: 71, Issue: 7, Pages: 1289-1303
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Abstract

Apolipoprotein CIII ApoCIII not only serves as an inhibitor of triglyceride hydrolysis but also participates in diabetesrelated pathological events such as hyperactivation of voltagegated Ca2+ CaV channels in the pancreatic β cell However nothing is known about the molecular mechanisms whereby ApoCIII hyperactivates β cell CaV channels We now demonstrate that ApoCIII increased CaV1 channel open probability and density ApoCIII enhanced wholecell Ca2+ currents and the CaV1 channel blocker nimodipine completely abrogated this enhancement The effect of ApoCIII was not influenced by individual inhibition of PKA PKC or Src However combined inhibition of PKA PKC and Src counteracted the effect of ApoCIII similar results obtained by coinhibition of PKA and Src Moreover knockdown of β1 integrin or scavenger receptor class B type I SRBI prevented ApoCIII from hyperactivating β cell CaV channels These data reveal that ApoCIII hyperactivates β cell CaV1 channels through SRBI/β1 integrindependent coactivation of PKA and SrcThis work was supported by grants from Berth von Kantzow’s Foundation Diabetes Research and Wellness Foundation EuroDia FP6518153 the Family ErlingPersson Foundation Fredrik and Ingrid Thuring’s Foundation Funds of Karolinska Institutet the Knut and Alice Wallenberg Foundation Magn Bergvall’s Foundation Novo Nordisk Foundation Skandia Insurance Company Ltd the Stichting af Jochnick Foundation Strategic Research Program in Diabetes at Karolinska Institutet the Swedish Alzheimer Association the Swedish Diabetes Association the Swedish Foundation for Strategic Research the Swedish Research Council the Swedish Society of Medicine Torsten and Ragnar Söderberg Foundation VIBRANT FP72289332 and Åke Wiberg’s Foundation PO Berggren is founder of the Biotech Company BioCrine AB and is also a member of the board of this company SNYang is a consultant to BioCrine AB BioCrine AB is developing ApoCIII as a novel druggable target for the treatment of diabetes

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