BiMe

The importance of metabolic reprogramming to cell function

date
27.09.2018 
time
11:00 AM - 12:00 PM 
speaker
Philip Newsholme 
affiliation
Curtin University Perth, Curtin Health Innovation Research Institute, Faculty of Health Sciences, School of Pharmacy and Biomedical Sciences 
part of series
CRTD External Seminar 
language
en 
main topic
Biology: Cell Biology (incl. Molecular, Structural), Developmental Biology, general
subtopics
Medicine: Regeneration, Immunology, Physiology, Diabetes, Pharmacology, general
host
Michele Solimena 
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 found that prolonged stimulation of the GLP-1R (18 hours) promoted metabolic reprogramming of β-cells. We determined up-regulation of glycolytic enzyme expression, increased rates of glucose uptake and consumption, as well as augmented ATP content, insulin secretion and glycolytic flux. 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.

 

Last update: 11.09.2018 10:09.

venue 

DFG Center for Regenerative Therapies Dresden (Auditorium left) 
Fetscherstraße 105
01307 Dresden
telefon
+49 (0)351 458 82064 
fax
+49 (0)351 458 82059  
e-mail
DFG Center for Regenerative Therapies Dresden 
homepage
http://www.crt-dresden.de 

organizer 

Paul Langerhans Institut Dresden (PLID)
Tatzberg 47-49
01307 Dresden
telefon
+49(0)3 51 79 63 66 18 
e-mail
Paul Langerhans Institut Dresden (PLID) 
homepage
http://www.plid.de 
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