UNIGE document Scientific Article
previous document  unige:116616  next document
add to browser collection
Title

Chronic fructose renders pancreatic beta-cells hyper-responsive to glucose-stimulated insulin secretion through extracellular ATP signaling

Authors show hidden authors show all authors [1 - 9]
Published in American Journal of Physiology. Endocrinology and Metabolism. 2019, vol. 317, no. 1, p. E25-E41
Abstract Fructose is widely used as a sweetener in processed food and since then is associated with metabolic disorders, such as obesity. However, the underlying cellular mechanisms remain unclear, in particular regarding the pancreatic beta-cell. Here, we investigated the effects of chronic exposure to fructose on the function of insulinoma cells and isolated mouse and human pancreatic islets. Although fructose per se did not acutely stimulate insulin exocytosis, our data show that chronic fructose rendered rodent and human beta-cells hyper-responsive to intermediate physiological glucose concentrations. Fructose exposure reduced intracellular ATP levels, without affecting mitochondrial function, induced AMPK activation and favored ATP release from the beta-cells upon acute glucose stimulation. The resulting increase in extracellular ATP, mediated by pannexin1 channels, activated the calcium-mobilizer P2Y purinergic receptors. Immunodetection revealed the presence of both pannexin1 channels and P2Y1 receptors in beta-cells. Addition of an ectonucleotidase inhibitor or P2Y1 agonists to naïve beta-cells potentiated insulin secretion stimulated by intermediate glucose, mimicking the fructose treatment. Conversely, P2Y1 antagonist and pannexin1 inhibitor reversed the effects of fructose, as confirmed using pannexin1-null islets and by the clearance of extracellular ATP by apyrase. These results reveal an important function of ATP signalling in pancreatic beta-cells mediating fructose-induced hyper-responsiveness.
Keywords Pancreatic isletInsulin secretionFructoseAMPKATPPannexinPurinergic receptor
Identifiers
PMID: 30912960
Full text
Article (Accepted version) (1.1 MB) - public document Free access
Appendix (1 MB) - public document Free access
Structures
Research groups L'athérosclérose (665)
Mitochondries et sécrétion d'insuline (671)
Mucoviscidose et jonctions communicantes (229)
La transplantation d'îlots de Langerhans (623)
Projects FNS: 146984
FNS: 166625
Citation
(ISO format)
BARTLEY, Clarissa et al. Chronic fructose renders pancreatic beta-cells hyper-responsive to glucose-stimulated insulin secretion through extracellular ATP signaling. In: American Journal of Physiology. Endocrinology and Metabolism, 2019, vol. 317, n° 1, p. E25-E41. doi: 10.1152/ajpendo.00456.2018 https://archive-ouverte.unige.ch/unige:116616

237 hits

181 downloads

Update

Deposited on : 2019-04-24

Export document
Format :
Citation style :