Storemoperated Ca2+ entry in insulin-releasing pancreatic β-cells

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

“…Consistent with previous studies [38,39] from the ER after SERCA inhibition was not restricted to -cells from ob/ob mice. As is shown in Fig.…”

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

“…Human ␤-cells were similar in this respect, but Ca 2ϩ -induced Ca 2ϩ release may be more prominent in the human cells explaining why peaks of near-membrane STIM1-YFP fluorescence interrupted glucose-induced STIM1 disappearance from the subplasmalemmal region. The physiological relevance of the glucose effects on ER Ca 2ϩ filling in ␤-cells is probably to secure a pool of releasable Ca 2ϩ rather than regulating the store-operated pathway, which has modest effects on [Ca 2ϩ ] i and insulin secretion (20,21,23,25). The glucose sensitivity of STIM1 retranslocation to the ER was strikingly higher in ␣-than in ␤-cells with maximal effect at 3 mM reinforcing indirect observations that this concentration is sufficient for maximal Ca 2ϩ filling of the ␣-cell ER (22).…”

“…The ␤-cell in Fig. 7A was initially exposed to 1.3 mM Ca 2ϩ and 3 mM glucose, which causes less than halfmaximal Ca 2ϩ filling of the ER (19) associated with partial inactivation of the store-operated pathway (21,25 ] i . The effect of such Ca 2ϩ omissionreaddition was not altered by forskolin (17 Ϯ 4 nM increase of [Ca 2ϩ ] i ; n ϭ 7).…”

“…Studies of the store-operated mechanism in primary ␤-cells (21,25) and ␣-cells (22) (26). We have now utilized adenoviruses encoding STIM1-YFP and Orai1-mCherry (16) to infect pancreatic islets and study STIM1 translocation and association with Orai1 in primary pancreatic islet cells during conditions known to modulate hormone secretion and SOCE.…”

Oscillatory control of insulin secretion

“…The importance of PLC activity for insulin secretion is underlined by the fact that the enzyme is activated not only after exposure of islets and β-cells to various G-protein coupled receptor stimuli, such as acetylcholine/carbachol (Best and Malaisse, 1983;Hellman and Gylfe, 1986a;Best et al, 1987;Biden et al, 1987;Gilon and Henquin, 2001) and ATP (Gylfe and Hellman, 1987;Blachier and Malaisse, 1988), but also after exposure to glucose (Axen et al, 1983;Best and Malaisse, 1983;Laychock, 1983;Montague et al, 1985) and depolarizing agents (Laychock, 1983;Mathias et al, 1985;Best et al, 1987;Biden et al, 1987;Zawalich and Zawalich, 1988 (Prentki et al, 1988;Gylfe, 1991;Hellman et al, 1992;Theler et al, 1992;Miura et al, 1996) and these oscillations are characterized by a much shorter period than the glucose-induced, slow oscillations described above. Most of the [Ca 2+ ] i -elevating effect is due to IP 3 -mediated Ca 2+ mobilization from the ER, but the emptying of the stores also triggers Ca 2+ entry through store-operated channels in the plasma membrane (Liu and Gylfe, 1997;Miura et al, 1997;Dyachok and Gylfe, 2001). Although the store-operated influx of Ca 2+ only causes a small elevation of [Ca 2+ ] i , this pathway may also contribute by its depolarizing effect.…”