Defective glucose-stimulated insulin secretion and Ca²⁺ transient in S2814D mice.

<p>(<b>A</b>) Insulin secretion from 4 sets of 5 islets each (each set from a different mouse, n = 20 islets from 4 mice per group) during 30-minute sequential exposures to glucose (2.8, 11 and 25 mM). Quantification revealed higher basal insulin secretion in islets from S2814D mice, which did not increase in response to glucose stimulation, compared to WT islets. (<b>B</b>) Representative tracings of [Ca²⁺]_cyt in WT and S2814D islets following glucose stimulation at varying concentrations (6, 8, and 10 mM). (<b>C</b>) Representative [Ca²⁺]_cyt tracings following stimulation with 40 mM KCl. (<b>D</b>) Quantification revealed blunted [Ca²⁺]_cyt transient amplitude in response to 10 mM glucose or 40 mM KCl in islets from S2814D mice compared to WT. In addition, frequency of [Ca²⁺]_cyt oscillations (<b>E</b>) and amplitude of [Ca²⁺]_cyt oscillations following initial peak (<b>F</b>) after 10 mM glucose stimulation were also reduced in S2814D islets. n = 6−14 islets from 3 mice per group. Data are represented as average ± SEM. *<i>P</i><0.05, **<i>P</i><0.01 vs. WT; ^#<i>P</i><0.05, ^##<i>P</i><0.01 vs. 2.8 mM glucose.