Short-term high glucose culture potentiates pancreatic beta cell function

Author(s)

Rebelato, Eduardo ^[1] ; Santos, Laila R. ^[2] ; Carpinelli, Angelo R. ^[3] ; Rorsman, Patrik ^[4] ; Abdulkader, Fernando ^[3]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil

^[2] Goethe Univ, Inst Vasc Signalling, Ctr Mol Med, Frankfurt - Germany

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[4] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford - England

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, AUG 30 2018.
• Web of Science Citations: 0

Abstract

The exposure of pancreatic islets to high glucose is believed to be one of the causal factors of the progressive lowering of insulin secretion in the development of type 2 diabetes. The progression of beta cell failure to type 2 diabetes is preceded by an early positive increase in the insulin secretory response to glucose, which is only later followed by a loss in the secretion capacity of pancreatic islets. Here we have investigated the electrophysiological mechanisms underlying the early glucose-mediated gain of function. Rodent pancreatic islets or dispersed islet cells were cultured in medium containing either 5.6 (control) or 16.7 (high-glucose) mM glucose for 24 h after isolation. Glucose-stimulated insulin secretion was enhanced in a concentration-dependent manner in high glucose-cultured islets. This was associated with a positive effect on beta cell exocytotic capacity, a lower basal K-ATP conductance and a higher glucose sensitivity to fire action potentials. Despite no changes in voltage-gated Ca2+ currents were observed in voltage-clamp experiments, the {[}Ca2+] I responses to glucose were drastically increased in high glucose-cultured cells. Of note, voltage-dependent K+ currents were decreased and their activation was shifted to more depolarized potentials by high-glucose culture. This decrease in voltage-dependent K+ channel (Kv) current may be responsible for the elevated {[}Ca2+] I response to metabolism-dependent and independent stimuli, associated with more depolarized membrane potentials with lower amplitude oscillations in high glucose-cultured beta cells. Overall these results show that beta cells improve their response to acute challenges after short-term culture with high glucose by a mechanism that involves modulation not only of metabolism but also of ion fluxes and exocytosis, in which Kv activity appears as an important regulator. (AU)

• FAPESP's process: 13/08769-1 - The role of NAD(P)H oxidase in the physiological and pathological molecular mechanisms of insulin secreting cells
• Grantee: Angelo Rafael Carpinelli
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/14826-0 - Signaling mechanisms for exocytosis in pancreatic beta cells
• Grantee: Eduardo Rebelato Lopes de Oliveira
• Support Opportunities: Research Grants - Young Investigators Grants