The importance of metabolic reprogramming to cell function

Datum

27.09.2018

Zeit

11:00 - 12:00

Sprecher

Philip Newsholme

Zugehörigkeit

Curtin University Perth, Curtin Health Innovation Research Institute, Faculty of Health Sciences, School of Pharmacy and Biomedical Sciences

Serie

CMCB Life Sciences Seminar

Sprache

en

Hauptthema

Biologie

Andere Themen

Biologie, Medizin

Host

Michele Solimena

Beschreibung

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.

Letztmalig verändert: 11.09.2018, 12:09:03