Sulfonylurea Blockade of KATP Channels Unmasks a Distinct Type of Glucose-Induced Ca2+ Decrease in Pancreatic β-CellsHellman, Bo MD, PhD; Dansk, Heléne; Grapengiesser, Eva PhDPancreas: April 2017 - Volume 46 - Issue 4 - p 467–475 doi: 10.1097/MPA.0000000000000777 Original Articles Abstract Author Information Objectives This study aimed to explore how sulfonylurea blockade of KATP channels affects the early Ca2+ signals for glucose generation of insulin release. Methods Cytoplasmic Ca2+ was measured with ratiometric microfluorometry in isolated mouse islets loaded with Fura-PE3. Results After sulfonylurea blockade of the KATP channels (50 μM-1 mM tolbutamide or 1 μM-1 mM gliclazide), increase of glucose from 3 to 20 mM resulted in suppression of elevated Ca2+ during a 3- to 5-minute period. The Ca2+ decrease was shorter after inhibition of the Na/K pump with ouabain (10 and 100 μM) but prolonged when the α2A adrenoceptors were activated with clonidine (1 and 10 nM) or epinephrine (10 nM). Inhibition of the sarco/endoplasmic reticulum Ca2+-ATPase pump with 10 μM cyclopiazonic acid counteracted the action of 10 nM clonidine, making the Ca2+ decrease shorter than in controls. Extended superfusion of islets with a medium containing 20 mM glucose and 1 mM tolbutamide sometimes resulted in delayed appearance of Ca2+ oscillations mediated by periodic interruption of elevated Ca2+. Conclusions Increase of glucose generates prompt suppression of cytoplasmic Ca2+ in β-cells lacking functional KATP channels. Activation of α2A adrenoceptors markedly prolongs the period of glucose-induced Ca2+ decrease, an effect counteracted by cyclopiazonic acid. From the Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Received for publication May 6, 2015; accepted October 7, 2016. Address correspondence to: Bo Hellman, MD, PhD, Biomedicum, Box 571, Husargatan 3, SE-75123 Uppsala, Sweden (e-mail: firstname.lastname@example.org). This study was supported by the Swedish Research Council (55x-06240) and the Swedish Diabetes Association. The authors declare no conflict of interest. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.