OcrV1, Main, Exploration, bibRecord, 000203

Deficiency of APPL1 in mice impairs glucose-stimulated insulin secretion through inhibition of pancreatic beta cell mitochondrial function

Identifieur interne : 000203 ( Main/Exploration ); précédent : 000202; suivant : 000204

Deficiency of APPL1 in mice impairs glucose-stimulated insulin secretion through inhibition of pancreatic beta cell mitochondrial function

Source :

Diabetologia : (Berlin) [ 0012-186X ] ; 2013.

RBID : Pascal:13-0281139

Descripteurs français

Pascal (Inist)
- Déficit, Glucose, Insuline, Sécrétion, Animal, Inhibition, Cellule β, Diabète, Mitochondrie, Adiponectine, Souris.
Wicri :
- topic : Déficit, Glucose, Diabète.

English descriptors

KwdEn :
- Adiponectin, Animal, Deficiency, Diabetes mellitus, Glucose, Inhibition, Insulin, Mitochondria, Mouse, Secretion, β Cell.

Abstract

Aims/hypothesis Adaptor protein, phosphotyrosine interaction, pleckstrin homology domain and leucine zipper containing 1 (APPL1) is an adapter protein that positively mediates adiponectin signalling. Deficiency of APPL1 in the target tissues of insulin induces insulin resistance. We therefore aimed, in the present study, to determine its role in regulating pancreatic beta cell function. Methods A hyperglycaemic clamp test was performed to determine insulin secretion in APPL1 knockout (KO) mice. Glucose- and adiponectin-induced insulin release was measured in islets from APPL1 KO mice or INS-1(832/13) cells with either APPL1 knockdown or overproduction. RT-PCR and western blotting were conducted to analyse gene expression and protein abundance. Oxygen consumption rate (OCR), ATP production and mitochondrial membrane potential were assayed to evaluate mitochondrial function. Results APPL1 is highly expressed in pancreatic islets, but its levels are decreased in mice fed a high-fat diet and db/db mice compared with controls. Deletion of the Appl1 gene leads to impairment of both the first and second phases of insulin secretion during hyperglycaemic clamp tests. In addition, glucose-stimulated insulin secretion (GSIS) is significantly decreased in islets from APPL1 KO mice. Conversely, overproduction of APPL1 leads to an increase in GSIS in beta cells. In addition, expression levels of several genes involved in insulin production, mitochondrial biogenesis and mitochondrial OCR, ATP production and mitochondrial membrane potential are reduced significantly in APPL1-knockdown beta cells. Moreover, suppression or overexproduction of APPL1 inhibits or stimulates adiponectin-potentiated GSIS in beta cells, respectively. Conclusions/interpretation Our study demonstrates the roles of APPL1 in regulating GSIS and mitochondrial function in pancreatic beta cells, which implicates APPL1 as a therapeutic target in the treatment of type 2 diabetes.

Affiliations:

Links toward previous steps (curation, corpus...)

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Le document en format XML

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<author><name sortKey="Mingliang Zhang" sort="Mingliang Zhang" uniqKey="Mingliang Zhang" last="Mingliang Zhang">MINGLIANG ZHANG</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road</s1>
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<author><name sortKey="Jiyoon Ryu" sort="Jiyoon Ryu" uniqKey="Jiyoon Ryu" last="Jiyoon Ryu">JIYOON RYU</name>
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<author><name sortKey="Zhifang Xie" sort="Zhifang Xie" uniqKey="Zhifang Xie" last="Zhifang Xie">ZHIFANG XIE</name>
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<author><name sortKey="Dongyun Shi" sort="Dongyun Shi" uniqKey="Dongyun Shi" last="Dongyun Shi">DONGYUN SHI</name>
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<author><name sortKey="Zhang, Weiping J" sort="Zhang, Weiping J" uniqKey="Zhang W" first="Weiping J." last="Zhang">Weiping J. Zhang</name>
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<author><name sortKey="Dong, Lily Q" sort="Dong, Lily Q" uniqKey="Dong L" first="Lily Q." last="Dong">Lily Q. Dong</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Deficiency of APPL1 in mice impairs glucose-stimulated insulin secretion through inhibition of pancreatic beta cell mitochondrial function</title>
<author><name sortKey="Chen Wang" sort="Chen Wang" uniqKey="Chen Wang" last="Chen Wang">CHEN WANG</name>
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<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai Key Laboratory of Diabetes Mellitus</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Xiaowen Li" sort="Xiaowen Li" uniqKey="Xiaowen Li" last="Xiaowen Li">XIAOWEN LI</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road</s1>
<s2>Shanghai 200233</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai 200233</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Diabetes Institute, Shanghai Jiao Tong University</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Shanghai Key Laboratory of Diabetes Mellitus</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai Key Laboratory of Diabetes Mellitus</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kaida Mu" sort="Kaida Mu" uniqKey="Kaida Mu" last="Kaida Mu">KAIDA MU</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road</s1>
<s2>Shanghai 200233</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai 200233</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Diabetes Institute, Shanghai Jiao Tong University</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
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<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Shanghai Key Laboratory of Diabetes Mellitus</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
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<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai Key Laboratory of Diabetes Mellitus</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ling Li" sort="Ling Li" uniqKey="Ling Li" last="Ling Li">LING LI</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road</s1>
<s2>Shanghai 200233</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai 200233</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Diabetes Institute, Shanghai Jiao Tong University</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Shanghai Key Laboratory of Diabetes Mellitus</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai Key Laboratory of Diabetes Mellitus</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Shihong Wang" sort="Shihong Wang" uniqKey="Shihong Wang" last="Shihong Wang">SHIHONG WANG</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road</s1>
<s2>Shanghai 200233</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai 200233</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Diabetes Institute, Shanghai Jiao Tong University</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Shanghai Key Laboratory of Diabetes Mellitus</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai Key Laboratory of Diabetes Mellitus</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yunxia Zhu" sort="Yunxia Zhu" uniqKey="Yunxia Zhu" last="Yunxia Zhu">YUNXIA ZHU</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road</s1>
<s2>Shanghai 200233</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
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<sZ>7 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai 200233</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Diabetes Institute, Shanghai Jiao Tong University</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Shanghai Key Laboratory of Diabetes Mellitus</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
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</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai Key Laboratory of Diabetes Mellitus</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mingliang Zhang" sort="Mingliang Zhang" uniqKey="Mingliang Zhang" last="Mingliang Zhang">MINGLIANG ZHANG</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road</s1>
<s2>Shanghai 200233</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai 200233</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Diabetes Institute, Shanghai Jiao Tong University</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Shanghai Key Laboratory of Diabetes Mellitus</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai Key Laboratory of Diabetes Mellitus</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jiyoon Ryu" sort="Jiyoon Ryu" uniqKey="Jiyoon Ryu" last="Jiyoon Ryu">JIYOON RYU</name>
<affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive</s1>
<s2>San Antonio, TX 78229-3900</s2>
<s3>USA</s3>
<sZ>8 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zhifang Xie" sort="Zhifang Xie" uniqKey="Zhifang Xie" last="Zhifang Xie">ZHIFANG XIE</name>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Pathophysiology, Second Military Medical University</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>9 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Dongyun Shi" sort="Dongyun Shi" uniqKey="Dongyun Shi" last="Dongyun Shi">DONGYUN SHI</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhang, Weiping J" sort="Zhang, Weiping J" uniqKey="Zhang W" first="Weiping J." last="Zhang">Weiping J. Zhang</name>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Pathophysiology, Second Military Medical University</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>9 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Dong, Lily Q" sort="Dong, Lily Q" uniqKey="Dong L" first="Lily Q." last="Dong">Lily Q. Dong</name>
<affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive</s1>
<s2>San Antonio, TX 78229-3900</s2>
<s3>USA</s3>
<sZ>8 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Weiping Jia" sort="Weiping Jia" uniqKey="Weiping Jia" last="Weiping Jia">WEIPING JIA</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Diabetes Institute, Shanghai Jiao Tong University</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Shanghai Key Laboratory of Diabetes Mellitus</s1>
<s2>Shanghai</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Shanghai Key Laboratory of Diabetes Mellitus</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Diabetologia : (Berlin)</title>
<title level="j" type="abbreviated">Diabetologia : (Berl.)</title>
<idno type="ISSN">0012-186X</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Diabetologia : (Berlin)</title>
<title level="j" type="abbreviated">Diabetologia : (Berl.)</title>
<idno type="ISSN">0012-186X</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adiponectin</term>
<term>Animal</term>
<term>Deficiency</term>
<term>Diabetes mellitus</term>
<term>Glucose</term>
<term>Inhibition</term>
<term>Insulin</term>
<term>Mitochondria</term>
<term>Mouse</term>
<term>Secretion</term>
<term>β Cell</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Déficit</term>
<term>Glucose</term>
<term>Insuline</term>
<term>Sécrétion</term>
<term>Animal</term>
<term>Inhibition</term>
<term>Cellule β</term>
<term>Diabète</term>
<term>Mitochondrie</term>
<term>Adiponectine</term>
<term>Souris</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Déficit</term>
<term>Glucose</term>
<term>Diabète</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Aims/hypothesis Adaptor protein, phosphotyrosine interaction, pleckstrin homology domain and leucine zipper containing 1 (APPL1) is an adapter protein that positively mediates adiponectin signalling. Deficiency of APPL1 in the target tissues of insulin induces insulin resistance. We therefore aimed, in the present study, to determine its role in regulating pancreatic beta cell function. Methods A hyperglycaemic clamp test was performed to determine insulin secretion in APPL1 knockout (KO) mice. Glucose- and adiponectin-induced insulin release was measured in islets from APPL1 KO mice or INS-1(832/13) cells with either APPL1 knockdown or overproduction. RT-PCR and western blotting were conducted to analyse gene expression and protein abundance. Oxygen consumption rate (OCR), ATP production and mitochondrial membrane potential were assayed to evaluate mitochondrial function. Results APPL1 is highly expressed in pancreatic islets, but its levels are decreased in mice fed a high-fat diet and db/db mice compared with controls. Deletion of the Appl1 gene leads to impairment of both the first and second phases of insulin secretion during hyperglycaemic clamp tests. In addition, glucose-stimulated insulin secretion (GSIS) is significantly decreased in islets from APPL1 KO mice. Conversely, overproduction of APPL1 leads to an increase in GSIS in beta cells. In addition, expression levels of several genes involved in insulin production, mitochondrial biogenesis and mitochondrial OCR, ATP production and mitochondrial membrane potential are reduced significantly in APPL1-knockdown beta cells. Moreover, suppression or overexproduction of APPL1 inhibits or stimulates adiponectin-potentiated GSIS in beta cells, respectively. Conclusions/interpretation Our study demonstrates the roles of APPL1 in regulating GSIS and mitochondrial function in pancreatic beta cells, which implicates APPL1 as a therapeutic target in the treatment of type 2 diabetes.</div>
</front>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Texas</li>
</region>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Chen Wang" sort="Chen Wang" uniqKey="Chen Wang" last="Chen Wang">CHEN WANG</name>
</noRegion>
<name sortKey="Chen Wang" sort="Chen Wang" uniqKey="Chen Wang" last="Chen Wang">CHEN WANG</name>
<name sortKey="Chen Wang" sort="Chen Wang" uniqKey="Chen Wang" last="Chen Wang">CHEN WANG</name>
<name sortKey="Dongyun Shi" sort="Dongyun Shi" uniqKey="Dongyun Shi" last="Dongyun Shi">DONGYUN SHI</name>
<name sortKey="Kaida Mu" sort="Kaida Mu" uniqKey="Kaida Mu" last="Kaida Mu">KAIDA MU</name>
<name sortKey="Kaida Mu" sort="Kaida Mu" uniqKey="Kaida Mu" last="Kaida Mu">KAIDA MU</name>
<name sortKey="Kaida Mu" sort="Kaida Mu" uniqKey="Kaida Mu" last="Kaida Mu">KAIDA MU</name>
<name sortKey="Ling Li" sort="Ling Li" uniqKey="Ling Li" last="Ling Li">LING LI</name>
<name sortKey="Ling Li" sort="Ling Li" uniqKey="Ling Li" last="Ling Li">LING LI</name>
<name sortKey="Ling Li" sort="Ling Li" uniqKey="Ling Li" last="Ling Li">LING LI</name>
<name sortKey="Mingliang Zhang" sort="Mingliang Zhang" uniqKey="Mingliang Zhang" last="Mingliang Zhang">MINGLIANG ZHANG</name>
<name sortKey="Mingliang Zhang" sort="Mingliang Zhang" uniqKey="Mingliang Zhang" last="Mingliang Zhang">MINGLIANG ZHANG</name>
<name sortKey="Mingliang Zhang" sort="Mingliang Zhang" uniqKey="Mingliang Zhang" last="Mingliang Zhang">MINGLIANG ZHANG</name>
<name sortKey="Shihong Wang" sort="Shihong Wang" uniqKey="Shihong Wang" last="Shihong Wang">SHIHONG WANG</name>
<name sortKey="Shihong Wang" sort="Shihong Wang" uniqKey="Shihong Wang" last="Shihong Wang">SHIHONG WANG</name>
<name sortKey="Shihong Wang" sort="Shihong Wang" uniqKey="Shihong Wang" last="Shihong Wang">SHIHONG WANG</name>
<name sortKey="Weiping Jia" sort="Weiping Jia" uniqKey="Weiping Jia" last="Weiping Jia">WEIPING JIA</name>
<name sortKey="Weiping Jia" sort="Weiping Jia" uniqKey="Weiping Jia" last="Weiping Jia">WEIPING JIA</name>
<name sortKey="Xiaowen Li" sort="Xiaowen Li" uniqKey="Xiaowen Li" last="Xiaowen Li">XIAOWEN LI</name>
<name sortKey="Xiaowen Li" sort="Xiaowen Li" uniqKey="Xiaowen Li" last="Xiaowen Li">XIAOWEN LI</name>
<name sortKey="Xiaowen Li" sort="Xiaowen Li" uniqKey="Xiaowen Li" last="Xiaowen Li">XIAOWEN LI</name>
<name sortKey="Yunxia Zhu" sort="Yunxia Zhu" uniqKey="Yunxia Zhu" last="Yunxia Zhu">YUNXIA ZHU</name>
<name sortKey="Yunxia Zhu" sort="Yunxia Zhu" uniqKey="Yunxia Zhu" last="Yunxia Zhu">YUNXIA ZHU</name>
<name sortKey="Yunxia Zhu" sort="Yunxia Zhu" uniqKey="Yunxia Zhu" last="Yunxia Zhu">YUNXIA ZHU</name>
<name sortKey="Zhang, Weiping J" sort="Zhang, Weiping J" uniqKey="Zhang W" first="Weiping J." last="Zhang">Weiping J. Zhang</name>
<name sortKey="Zhifang Xie" sort="Zhifang Xie" uniqKey="Zhifang Xie" last="Zhifang Xie">ZHIFANG XIE</name>
</country>
<country name="États-Unis"><region name="Texas"><name sortKey="Jiyoon Ryu" sort="Jiyoon Ryu" uniqKey="Jiyoon Ryu" last="Jiyoon Ryu">JIYOON RYU</name>
</region>
<name sortKey="Dong, Lily Q" sort="Dong, Lily Q" uniqKey="Dong L" first="Lily Q." last="Dong">Lily Q. Dong</name>
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   |texte=   Deficiency of APPL1 in mice impairs glucose-stimulated insulin secretion through inhibition of pancreatic beta cell mitochondrial function
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Deficiency of APPL1 in mice impairs glucose-stimulated insulin secretion through inhibition of pancreatic beta cell mitochondrial function

Deficiency of APPL1 in mice impairs glucose-stimulated insulin secretion through inhibition of pancreatic beta cell mitochondrial function

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