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Published on: May 2, 2019
Expression, phosphorylation and function of the Rab-GTPase activating protein TBC1D1 in pancreatic beta-cells
Sabine Rütti1, Caroline Arous1, Alexandra C Nica1
1Department of Genetic Medicine and Development, University Medical Center, University of Geneva, Geneva, Switzerland.
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.
Insights
The Rab-GTPase activating protein TBC1D1 is expressed in beta-cells and influences insulin release and proliferation. Its role in beta-cell function and survival is now clearer.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- TBC1D1 is a Rab-GTPase activating protein and paralog of AS160/TBC1D4.
- AS160/TBC1D4 is crucial for beta-cell function and survival, acting as a downstream effector of Akt.
- The expression and function of TBC1D1 in beta-cells were previously unknown.
Purpose of the Study:
- To determine if TBC1D1 is expressed in beta-cells.
- To investigate the role of TBC1D1 in beta-cell function and survival.
- To compare TBC1D1's role with that of AS160/TBC1D4.
Main Methods:
- Utilized human and rat beta-cells.
- Examined TBC1D1 expression and phosphorylation in response to glucose.
- Performed TBC1D1 knockdown experiments in beta-cells.
Main Results:
- TBC1D1 is expressed and phosphorylated in response to glucose in beta-cells.
- TBC1D1 knockdown led to increased basal and glucose-stimulated insulin release.
- TBC1D1 knockdown resulted in decreased beta-cell proliferation but did not affect apoptosis.
Conclusions:
- TBC1D1 is present and regulated by glucose in beta-cells.
- TBC1D1 plays a significant role in modulating insulin secretion and beta-cell proliferation.
- TBC1D1 is a novel factor influencing beta-cell physiology.
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