Adenoviral Gene Transfer of PLD1-D4 Enhances Insulin Sensitivity in Mice by Disrupting Phospholipase D1 Interaction with PED/PEA-15 (Publication with Expression of Concern. See vol. 17, 2022) (Publication with Expression of Concern. See vol. 17, 2022)

被引：10

作者：

Cassese, Angela ^{[1
,2
]}

Raciti, Gregory A. ^{[1
,2
]}

Fiory, Francesca ^{[1
,2
]}

Nigro, Cecilia ^{[1
,2
]}

Ulianich, Luca ^{[1
,2
]}

Castano, Ilenia ^{[3
,4
]}

D'Esposito, Vittoria ^{[1
,2
]}

Terracciano, Daniela ^{[1
,2
]}

Pastore, Lucio ^{[3
,4
]}

Formisano, Pietro ^{[1
]}

Beguinot, Francesco ^{[1
,2
]}

Miele, Claudia ^{[1
,2
]}

机构：

[1] Univ Naples Federico II, Dipartimento Sci Med & Traslazionali, Naples, Italy

[2] CNR, Ist Endocrinol & Oncol Sperimentale Gaetano Salva, Naples, Italy

[3] Univ Naples Federico II, Dipartimento Biochim & Biotecnol Med, Naples, Italy

[4] CEINGE Biotecnol Avanzate, Naples, Italy

来源：

PLOS ONE | 2013年 / 8卷 / 04期

关键词：

PROTEIN-KINASE-C; ADP-RIBOSYLATION FACTOR; GLUCOSE-TRANSPORT; ACTIVATION; EXPRESSION; RAT; INVOLVEMENT; SECRETION; ISOFORMS; BETA;

D O I：

10.1371/journal.pone.0060555

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Over-expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15) causes insulin resistance by interacting with the D4 domain of phospholipase D1 (PLD1). Indeed, the disruption of this association restores insulin sensitivity in cultured cells over-expressing PED/PEA-15. Whether the displacement of PLD1 from PED/PEA-15 improves insulin sensitivity in vivo has not been explored yet. In this work we show that treatment with a recombinant adenoviral vector containing the human D4 cDNA (Ad-D4) restores normal glucose homeostasis in transgenic mice overexpressing PED/PEA-15 (Tg (ped/pea-15)) by improving both insulin sensitivity and secretion. In skeletal muscle of these mice, D4 over-expression inhibited PED/PEA-15-PLD1 interaction, decreased Protein Kinase C alpha activation and restored insulin induced Protein Kinase C zeta activation, leading to amelioration of insulin-dependent glucose uptake. Interestingly, Ad-D4 administration improved insulin sensitivity also in high-fat diet treated obese C57Bl/6 mice. We conclude that PED/PEA-15-PLD1 interaction may represent a novel target for interventions aiming at improving glucose tolerance.

引用

页数：11

共 29 条

[1]

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