Differential Effect of Nutrient and Non-Nutrient Secretagogues on Cytosolic Free Ca2+ in Pancreatic Islet Cells
Glucose may increase cytosolic free Ca2+ ([Ca2+]i) in the pancreatic β-cell by increasing Ca2+-inflow. Whether glucose may also increase [Ca2+]i by inhibiting Ca2+-extrusion by Na2+/Ca2+ exchange, remains a matter of debate. Cytosolic free Ca2+ was measured in rat pancreatic islets using the Ca2+ indicator Quin 2. The mean [Ca2+]i, in the presence of 1.7 mM glucose, was 109 ± 9 nM (n = 21). A rise in the glucose concentration from 1.7 mM to 16.7 mM induced a biphasic increase in [Ca2+]i which reached a value of about 640 nM after 15 min. This increase was doubled in the presence of tetraethylammonium (20 mM), reduced by nifedipine (1 μM) and abolished by mannoheptulose (20 mM). Glucose (16.7 mM) also increased, although to a lower extent, [Ca2+]i in the absence of extracellular Ca2+ or at a non-insulinotropic concentration (4.2 mM) in the presence of extracellular Ca2+. However, the effect of glucose (16.7 mM) was abolished in the absence of both extracellular Ca2+ and Na2+. Other nutrient secretagogues (e.g. mannose and alanine) also induced a biphasic increase in [Ca2+]i which persisted in the absence of extracellular Ca2+. In contrast, non-nutrient secretagogues [e.g. 20 mM K+ or the sulfonylurea gliclazide (15 μg/ml)] induced a monophasic increase in [Ca2+]i which was completely suppressed in the absence of extracellular Ca2+.