Modulation of glucose-induced insulin secretion by cytosolic redox state in clonal β-cells

摘要: Abstract Nutrient stimulation of pancreatic β-cells increases the cellular reduced pyridine nucleotide content, but specific role cytosolic redox state in glucose-induced insulin release (GIIR) remains undetermined. The has been assessed (as reflected by lactate/pyruvate ratio) nutrient- and non-nutrient-induced using a recently established glucose-sensitive clonal β-cell line (BRIN-BD11). Long-term exposure to NAD+ precursor vitamin nicotinic acid (NA, 100 μM) was used promote more oxidized cytosol. Glucose (2–16 mM) evoked dose-dependent rise NADH/NAD+ ratio which linearly related extent GIIR. NA suppressed concomitantly GIIR 44%. It also inhibited, 47%, average free Ca2+ concentration ([Ca2+]i, fura-2 microfluorometry from single cells). latter effect not accounted for reduction activity voltage-sensitive channels, inasmuch as both high K+- tolbutamide-induced [Ca2+]i rises remained insensitive exposure. did affect any depolarizing agents, indicating that steps stimulus-secretion coupling cascade distal influx are changes state. is concluded partially controlled Moreover, impairment GIIR, caused shift toward cytosol, originates an attenuated response. likely mediated influence on metabolic pathways (NADH shuttle systems and/or malonyl-CoA pathway), leading ultimately enhancement ATP-sensitive K+ channels.