Endocrinology, Vol 119, 2502-2507, Copyright © 1986 by Endocrine Society

ARTICLES

Glucose induces insulin release and a rise in cytosolic calcium concentration in a transplantable rat insulinoma

M Hoenig and GW Sharp

An important role for calcium in the cellular events leading to insulin secretion is supported by many studies. However, simultaneous measurements of changes in intracellular free Ca2+ concentrations [( Ca2+]i) and insulin release in response to secretagogues have not been performed. Using cells isolated from a glucose-responsive insulinoma, changes in [Ca2+]i were measured with the fluorescent calcium probe quin2. With the nutrient secretagogues glucose (30 mM) and D,L- glyceraldehyde (GA; 20 mM), [Ca2+]i increased slowly, reaching a peak approximately 15 min after addition of the stimulus, while KCl (25 mM) and carbachol (2 mM) led to a rapid but transient increase in [Ca2+]i. Glucose increased [Ca2+]i from 104 +/- 6 (mean +/- SEM) to 248 +/- 31 mM (n = 13), and GA caused a rise in [Ca2+]i from 96 +/- 6 to 280 +/- 39 nM (n = 4). KCl and carbachol caused a rise from 107 +/- 6 to 184 +/- 5 nM and from 98 +/- 5 to 157 +/- 5 nM, respectively (n = 5 each). When insulin release was measured simultaneously with changes in [Ca2+]i and compared to unstimulated cells, the following results were obtained. During the first 5 min of stimulation, high glucose caused a 90 +/- 12% increase in insulin release and a 72 +/- 11% rise in [Ca2+]i (n = 5). GA evoked a 122 +/- 30% increase in insulin secretion, with a 82 +/- 17% rise in [Ca2+]i (n = 3). Both KCl and carbachol caused a 58 +/- 9% increase in insulin release, with 7 +/- 4% and 50 +/- 2% rises in [Ca2+]i, respectively (n = 4 each). Insulin release was also measured in a perifusion system. It was shown that glucose (30 mM), GA (20 mM), and alpha-ketoisocaproate (30 mM) caused a biphasic release of insulin, while KCl (25 mM) and carbachol (2 mM) caused a monophasic release. The results show that [Ca2+]i increases during the stimulation of insulin secretion when measured simultaneously on the same beta-cells. However, while these changes coincide, a simple direct quantitative relationship between insulin release and the rise in [Ca2+]i could not be demonstrated.

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