Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells

Sabine Rütti; Caroline Arous; Alexandra C. Nica; Makoto Kanzaki; Philippe A. Halban; Karim Bouzakri

doi:10.1016/j.febslet.2013.10.050

Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells

Sabine Rütti, Caroline Arous, Alexandra C. Nica, Makoto Kanzaki, Philippe A. Halban, Karim Bouzakri

MEN - Biomedical Engineering

University of Geneva

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

The Rab-GTPase activating protein TBC1D1 is a paralog of AS160/TBC1D4. AS160/TBC1D4, a downstream effector of Akt, has been shown to play a central role in beta-cell function and survival. The two proteins have overlapping function in insulin signalling in muscle cells. However, the expression and the potential role of TBC1D1 in beta-cells remain unknown. Therefore, the aim of this study is to investigate whether TBC1D1 is expressed in beta-cells and whether it plays, as AS160/TBC1D4, a role in beta-cell function and survival. Using human and rat beta-cells, this study shows for the first time that TBC1D1 is expressed and phosphorylated in response to glucose in these cells. Knockdown of TBC1D1 in beta-cells resulted in increased basal and glucose-stimulated insulin release, decreased proliferation but no change in apoptosis.

Original language	English
Pages (from-to)	15-20
Number of pages	6
Journal	FEBS Letters
Volume	588
Issue number	1
DOIs	https://doi.org/10.1016/j.febslet.2013.10.050
Publication status	Published - 2014 Jan 3

Keywords

Apoptosis
Beta-cell
Glucose response
Proliferation
TBC1D1

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10.1016/j.febslet.2013.10.050

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title = "Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells",

abstract = "The Rab-GTPase activating protein TBC1D1 is a paralog of AS160/TBC1D4. AS160/TBC1D4, a downstream effector of Akt, has been shown to play a central role in beta-cell function and survival. The two proteins have overlapping function in insulin signalling in muscle cells. However, the expression and the potential role of TBC1D1 in beta-cells remain unknown. Therefore, the aim of this study is to investigate whether TBC1D1 is expressed in beta-cells and whether it plays, as AS160/TBC1D4, a role in beta-cell function and survival. Using human and rat beta-cells, this study shows for the first time that TBC1D1 is expressed and phosphorylated in response to glucose in these cells. Knockdown of TBC1D1 in beta-cells resulted in increased basal and glucose-stimulated insulin release, decreased proliferation but no change in apoptosis.",

keywords = "Apoptosis, Beta-cell, Glucose response, Proliferation, TBC1D1",

author = "Sabine R{\"u}tti and Caroline Arous and Nica, {Alexandra C.} and Makoto Kanzaki and Halban, {Philippe A.} and Karim Bouzakri",

note = "Funding Information: Human islets were kindly provided by the Islet for Basic Research program through the European Consortium for Islet Transplantation, supported by the Juvenile Diabetes Research Foundation ( JDRF award 31-2008-413 ). This work was supported by the Swiss National Science Foundation (Grant No. 31003A_135645/1 to K.B. and 31003A_144092/1 to P.A.H.). We thank Melanie Cornut, Katharina Rickenbach and St{\'e}phane Dupuis for expert technical assistance.",

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AU - Kanzaki, Makoto

AU - Halban, Philippe A.

AU - Bouzakri, Karim

N1 - Funding Information: Human islets were kindly provided by the Islet for Basic Research program through the European Consortium for Islet Transplantation, supported by the Juvenile Diabetes Research Foundation ( JDRF award 31-2008-413 ). This work was supported by the Swiss National Science Foundation (Grant No. 31003A_135645/1 to K.B. and 31003A_144092/1 to P.A.H.). We thank Melanie Cornut, Katharina Rickenbach and Stéphane Dupuis for expert technical assistance.

PY - 2014/1/3

Y1 - 2014/1/3

N2 - The Rab-GTPase activating protein TBC1D1 is a paralog of AS160/TBC1D4. AS160/TBC1D4, a downstream effector of Akt, has been shown to play a central role in beta-cell function and survival. The two proteins have overlapping function in insulin signalling in muscle cells. However, the expression and the potential role of TBC1D1 in beta-cells remain unknown. Therefore, the aim of this study is to investigate whether TBC1D1 is expressed in beta-cells and whether it plays, as AS160/TBC1D4, a role in beta-cell function and survival. Using human and rat beta-cells, this study shows for the first time that TBC1D1 is expressed and phosphorylated in response to glucose in these cells. Knockdown of TBC1D1 in beta-cells resulted in increased basal and glucose-stimulated insulin release, decreased proliferation but no change in apoptosis.

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Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells

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Keywords

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