Effects of CaMKII-Mediated Phosphorylation of Ryanodine Receptor Type 2 on Islet Calcium Handling, Insulin Secretion, and Glucose Tolerance (original) (raw)
Figure 5
Reduced glucose-sensitive Ca2+ pools and the putative mechanism underlying glucose-metabolism defects in S2814D mice.
(A) Representative [Ca2+]cyt tracings in islets isolated from WT and S2814D mice following stimulation with 5 µM thapsigargin (TG). (B) Quantification of [Ca2+]cyt transient rise per sec in response to 5 µM TG in islets from WT and S2814D mice. Data are represented as average ± SEM. n = 19−24 islets from 3–5 mice per group. **P<0.01 versus WT. (C) Mutation S2814D results in reduced glucose-sensitive Ca2+ pools in islets from S2814D mice. (1) Due to S2814D mutation, RyR2 leaks Ca2+ from intracellular Ca2+ stores in pancreatic β cells. (2) Chronic Ca2+ leak, in turn, leads to (dotted arrow) a decrease (downward arrow) in the glucose-sensitive Ca2+ pool in S2814D mice. (3) This decrease in the Ca2+ pool is reflected by a decrease in glucose-stimulated intracellular Ca2+ transients, which (4) blunts glucose-stimulated insulin secretion in S2814D mice.