2014 Fiscal Year Final Research Report
The role of nuclear pore complex in the regulation of glucose and lipid metabolism
| Project/Area Number |
25670159
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Gunma University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | Chrebp / 核膜孔 |
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| Outline of Final Research Achievements |
We show that carbohydrate response element binding protein (ChREBP), a glucose-regulated transcription factor, is O-glycosylated by OGT, leading to increased ChREBP levels, owing to decreased ubiquitination. Conversely, expression of O-GlcNAcase (GCA) in hepatocytes decreases ChREBP O-glycosylation, thus reducing its protein levels. FoxO1, a downstream effector of insulin signaling, has been known to regulate glucose metabolism in liver. We show here that FoxO1 overexpression inhibits ChREBP O-glycosylation in hepatocytes, thus reducing ChREBP levels. Conversely, conditional FoxO1 knockout in liver results in increased levels of O-glycosylated ChREBP, even in the fasted state. O-glycosylation is an important mechanism to regulate ChREBP function, and that FoxO1 is required for ChREBP O-glycosylation. We propose that FoxO1 is the shared signaling element linking glucose- and insulin-activated pathways to regulate hepatic glucose metabolism.
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| Free Research Field |
糖尿病
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