Abstract

The neuropeptide gastrin releasing peptide (GRP) stimulates insulin secretion and induces oscillations of the cytoplasmic Ca2+ concentration ([Ca2+]cyt) in clonal insulinoma cells. It is not known whether GRP affects [Ca2+]cyt in normal beta cells. We investigated, in single, normal, mouse islet beta cells, the effects of GRP on [Ca2+]cyt, by dual wavelength spectrophotofluorometry. Beta cells were identified by their typical response to glucose or tolbutamide. At 15 mM glucose, GRP (100 nM) evoked an immediate [Ca2+]cyt transient to 423 ± 48 nM compared to 126 ± 18 nM before GRP (P < 0.001). After the initial transient, [Ca2+]cyt exhibited either a sustained elevation or oscillations. At 3.3 mM glucose, in cells with a non-oscillating [Ca2+]cyt, GRP stimulated a prompt increase in [Ca2+]cyt (from 60 ± 6 to 285 ± 30 nM, P = 0.024) followed by either a sustained increase in [Ca2+]cyt or [Ca2+]cyt oscillations. We conclude that GRP promptly elevates [Ca2+]cyt by a direct action in normal mouse pancreatic beta cells.

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