Glucose Regulation of Free Ca2+ in the Endoplasmic Reticulum of Mouse Pancreatic Beta Cells

cAMP Induces Stromal Interaction Molecule 1 (STIM1) Puncta but neither Orai1 Protein Clustering nor Store-operated Ca2+ Entry (SOCE) in Islet Cells

“…An early effect of glucose stimulation is therefore to energize the SERCA pump causing calcium sequestration in the ER, lowering of [Ca 2ϩ ] i (20,43) and initial inhibition of insulin secretion (44,45 gers a pronounced peak of secretion replacing the initial inhibition (46). ER sequestration of Ca 2ϩ is half-maximal and maximal at about 6 and 20 mM glucose, respectively (19,(47)(48)(49). It is well documented that Ca 2ϩ emptying of the ER activates SOCE in ␤-cells (19 -21, 23, 25, 50), and the rate of SOCE is inversely dependent on the Ca 2ϩ filling of the ER in a graded fashion (25).…”

Oscillatory control of insulin secretion

“…The initial rise of [Ca 2+ ] i is preceded by a lowering ( (Grapengiesser et al, 1988a); Figure 2A) that essentially reflects ATP-stimulated Ca 2+ sequestration in the endoplasmic reticulum (ER; (Tengholm et al, 1999)) that becomes masked when depolarization has reached the threshold for voltage-dependent Ca 2+ entry (Chow et al, 1995). The lowering is prevented by inhibiting the sarco(endo)plasmic reticulum Ca 2+ ATPase (SERCA; (Chow et al, 1995)) and has been attributed to a high affinity SERCA2 mechanism, since it remains after ablation of the low affinity SERCA3 transporter (Arredouani et al, 2002).…”

Ca2+-induced Ca2+ release by activation of inositol 1,4,5-trisphosphate receptors in primary pancreatic β-cells

“…Studying the effects of SERCA inhibition on [Ca 2+ ] i , we ensured maximal initial filling of the ER by exposing the -cells to 20 mM glucose, which stimulates Ca 2+ sequestration in this organelle even when [Ca 2+ ] i is kept at resting levels [35][36][37]. Interference from voltage-dependent Ca 2+ entry was avoided by the presence of hyperpolarizing diazoxide as well as the L-type Ca 2+ channel blocker methoxyverapamil [35,38].…”