Na(+)-Ca2+ exchange may play a role in Ca2+ extrusion from the pancreatic B-cell. The characteristics of the process working in its reverse mode were examined in normal rat pancreatic islet cells. Isosmotical replacement of extracellular Na+ by sucrose induced a concentration-dependent increase in 45Ca uptake, displaying a pharmacological sensitivity compatible with an uptake mediated by Na(+)-Ca2+ exchange. Glucose, up to 2.8 mM, stimulated reverse Na(+)-Ca2+ exchange. Likewise, membrane depolarization activated the process but only under raised intracellular Na+ activity. In conclusion, the B-cell Na(+)-Ca2+ exchange displays properties similar to those observed in other cells: reversibility and sensitivity to membrane potential. When working in its reverse mode the exchanger displays a quite large capacity. The role played by the exchanger in the process of insulin release warrants further investigation.
The possible relevance of changes in extracellular and/or intracellular pH to the insulinotropic action of L-arginine and L-homoarginine was investigated in rat pancreatic islets. A rise in extracellular pH from 7.0 to 7.4 and 7.8 augmented the secretory response to these cationic amino acids whilst failing to affect the uptake of L-arginine by islet cells and whilst decreasing the release of insulin evoked by D-glucose. Under these conditions, a qualified dissociation was also observed between secretory data and 45Ca net uptake. Moreover, at high extracellular pH, the homoarginine-induced increase in 86Rb outflow from prelabelled islets rapidly faded out, despite sustained stimulation of insulin release. The cationic amino acids failed to affect the intracellular pH of islet cells, whether in the absence or presence of D-glucose and whether at normal or abnormal extracellular pH. These findings argue against the view that the secretory response to L-arginine would be related to either a change in cytosolic pH or the accumulation of this positively charged amino acid in the beta-cell. Nevertheless, they suggest that the yet unidentified target for L-arginine and its non-metabolized analogue in islet cells displays pH-dependency with optimal responsiveness at alkaline pH.
In cultured neonatal islet cells, glucose (16.7 mM) and K+ (50 mM) increased cytosolic free Ca2+ ([Ca2+]i). The increments in [Ca2+]i induced by either glucose or K+ were similar to those obtained in cultured adult islet cells but only half of that recorded in freshly isolated adult islet cells. These data indicate that, in neonatal islet cells, the reduced insulin release in response to glucose is associated with a diminished increase in [Ca2+]i. This reduced insulin response may not solely be due to an impaired regulation of the ATP-sensitive K+ channels as previously suggested. It may also result from some alteration in the process of Ca2+ inflow through voltage-sensitive Ca2+ channels.
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