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CLASS: Professor Philip Newholme, Curtin University Perth

Date: 20 March 2018

Venue: UCD Conway Lecture Theatre

Time: 12 noon

SpeakerProfessor Philip Newholme, Curtin University Perth

Title: 'The importance of metabolic reprogramming to cell function’

Abstract:
Glucagon-like-peptide-1 (GLP-1) promotes insulin secretion from pancreatic β-cells in a glucose dependent manner. Several pathways mediate this action by rapid, kinase phosphorylation-dependent, but gene expression-independent mechanisms. GLP-1-induced insulin secretion requires glucose metabolism, therefore GLP-1 receptor (GLP-1R) signalling may impact glucose uptake and utilization in β-cells. By determination of changes to various metabolic parameters after short and long exposure of clonal BRIN-BD11 β-cells and rodent islets to the GLP-1R agonist Exendin-4 (50 nM), we have found that prolonged stimulation of the GLP-1R (18 hours) promoted metabolic reprogramming of β-cells. This was evidenced by up-regulation of glycolytic enzyme expression, increased rates of glucose uptake and consumption, as well as augmented ATP content, insulin secretion and glycolytic flux after removal of Exendin-4. In our model, depletion of Hypoxia-Inducible Factor 1 alpha (HIF-1α) impaired the effects of Exendin-4 on glucose metabolism, while pharmacological inhibition of Phosphoinositide 3-kinase (PI3K) or mTOR completely abolished such effects. Considering the central role of glucose catabolism for stimulus-secretion coupling in β-cells, our findings suggest that chronic GLP-1 actions on insulin secretion include elevated β-cell glucose metabolism. In this presentation, I will also briefly describe the importance of metabolic reprogramming to immune cell function.

Refreshments available outside the lecture theatre from 11.40am

Upcoming CLASS

March

27 Professor Bruce Cronstein, New York University

April

03 Easter 
10 Dr Christina Kiel, Systems Biology Ireland 
17 Prof. Dominique Baeten, UVA Nederlands
24 Dr Ronan Sulpice, NUI Galway

Associate sponsors of the Conway Lecture & Seminar Series 2017/2018

BioSciences  Cruinn Diagnostics Ltd ‌

 

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