Abstract
The effects of galanin and somatostatin on insulin release, membrane potential, and cytoplasmic free Ca2+ concentration ([Ca2+](i)) were investigated using β-cells isolated from obese hyperglycemic mice. Whereas insulin release was measured in a column perifusion system, membrane potential and [Ca2+](i) were measured with the fluorescent indicators bisoxonol (bis-(1,3-diethylthiobarbiturate)trimethineoxonol) and quin 2, in cell suspensions in a cuvette. Galanin (16 nM) and somatostatin (400 nM) suppressed glucose-stimulated insulin release in parallel to promoting repolarization and a reduction in [Ca2+](i). The reduction in [Ca2+](i) comprised an initial nadir followed by a slow rise and the establishment of a new steady state level. The slow rise in [Ca2+](i) was abolished by 50 μM D-600, a blocker of voltage-activated Ca2+ channels. Both peptides suppressed insulin release even when [Ca2+](i) was raised by 25 mM K+. Under these conditions the inhibition of insulin release was partly reversed by an increase in the glucose concentration. Addition of 5 mM Ca2+ to a cell suspension, incubated in the presence of 20 mM glucose and either galanin, somatostatin, or the α2-adrenergic agonist clonidine (10 nM), induced oscillations in [Ca2+](i), this effect disappearing subsequent to the addition of D-600. The effects of galanin, somatostatin, and clonidine on [Ca2+](i) were abolished in β-cells treated with pertussis toxin. In accordance with measurements of [Ca2+](i) treatment with pertussis toxin reversed the inhibitory effect of galanin on insulin release. The inhibitory action of galanin and somatostatin on insulin release is probably accounted for by not only a repolarization-induced reduction in [Ca2+](i) and a decreased sensitivity of the secretory machinery to Ca2+, but also by a direct interaction with the exocytotic process. It is proposed that these effects are mediated by a pertussis toxin-sensitive GTP-binding protein.
| Original language | English |
|---|---|
| Pages (from-to) | 973-980 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 264 |
| Issue number | 2 |
| State | Published - Jan 1 1989 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Suppression of insulin release by galanin and somatostatin is mediated by a G-protein. An effect involving repolarization and reduction in cytoplasmic free Ca2+ concentration. / Nilsson, T.; Arkhammar, P.; Rorsman, P.; Berggren, P. O.
In: Journal of Biological Chemistry, Vol. 264, No. 2, 01.01.1989, p. 973-980.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Suppression of insulin release by galanin and somatostatin is mediated by a G-protein. An effect involving repolarization and reduction in cytoplasmic free Ca2+ concentration
AU - Nilsson, T.
AU - Arkhammar, P.
AU - Rorsman, P.
AU - Berggren, P. O.
PY - 1989/1/1
Y1 - 1989/1/1
N2 - The effects of galanin and somatostatin on insulin release, membrane potential, and cytoplasmic free Ca2+ concentration ([Ca2+](i)) were investigated using β-cells isolated from obese hyperglycemic mice. Whereas insulin release was measured in a column perifusion system, membrane potential and [Ca2+](i) were measured with the fluorescent indicators bisoxonol (bis-(1,3-diethylthiobarbiturate)trimethineoxonol) and quin 2, in cell suspensions in a cuvette. Galanin (16 nM) and somatostatin (400 nM) suppressed glucose-stimulated insulin release in parallel to promoting repolarization and a reduction in [Ca2+](i). The reduction in [Ca2+](i) comprised an initial nadir followed by a slow rise and the establishment of a new steady state level. The slow rise in [Ca2+](i) was abolished by 50 μM D-600, a blocker of voltage-activated Ca2+ channels. Both peptides suppressed insulin release even when [Ca2+](i) was raised by 25 mM K+. Under these conditions the inhibition of insulin release was partly reversed by an increase in the glucose concentration. Addition of 5 mM Ca2+ to a cell suspension, incubated in the presence of 20 mM glucose and either galanin, somatostatin, or the α2-adrenergic agonist clonidine (10 nM), induced oscillations in [Ca2+](i), this effect disappearing subsequent to the addition of D-600. The effects of galanin, somatostatin, and clonidine on [Ca2+](i) were abolished in β-cells treated with pertussis toxin. In accordance with measurements of [Ca2+](i) treatment with pertussis toxin reversed the inhibitory effect of galanin on insulin release. The inhibitory action of galanin and somatostatin on insulin release is probably accounted for by not only a repolarization-induced reduction in [Ca2+](i) and a decreased sensitivity of the secretory machinery to Ca2+, but also by a direct interaction with the exocytotic process. It is proposed that these effects are mediated by a pertussis toxin-sensitive GTP-binding protein.
AB - The effects of galanin and somatostatin on insulin release, membrane potential, and cytoplasmic free Ca2+ concentration ([Ca2+](i)) were investigated using β-cells isolated from obese hyperglycemic mice. Whereas insulin release was measured in a column perifusion system, membrane potential and [Ca2+](i) were measured with the fluorescent indicators bisoxonol (bis-(1,3-diethylthiobarbiturate)trimethineoxonol) and quin 2, in cell suspensions in a cuvette. Galanin (16 nM) and somatostatin (400 nM) suppressed glucose-stimulated insulin release in parallel to promoting repolarization and a reduction in [Ca2+](i). The reduction in [Ca2+](i) comprised an initial nadir followed by a slow rise and the establishment of a new steady state level. The slow rise in [Ca2+](i) was abolished by 50 μM D-600, a blocker of voltage-activated Ca2+ channels. Both peptides suppressed insulin release even when [Ca2+](i) was raised by 25 mM K+. Under these conditions the inhibition of insulin release was partly reversed by an increase in the glucose concentration. Addition of 5 mM Ca2+ to a cell suspension, incubated in the presence of 20 mM glucose and either galanin, somatostatin, or the α2-adrenergic agonist clonidine (10 nM), induced oscillations in [Ca2+](i), this effect disappearing subsequent to the addition of D-600. The effects of galanin, somatostatin, and clonidine on [Ca2+](i) were abolished in β-cells treated with pertussis toxin. In accordance with measurements of [Ca2+](i) treatment with pertussis toxin reversed the inhibitory effect of galanin on insulin release. The inhibitory action of galanin and somatostatin on insulin release is probably accounted for by not only a repolarization-induced reduction in [Ca2+](i) and a decreased sensitivity of the secretory machinery to Ca2+, but also by a direct interaction with the exocytotic process. It is proposed that these effects are mediated by a pertussis toxin-sensitive GTP-binding protein.
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M3 - Article
C2 - 2463254
AN - SCOPUS:0024545078
VL - 264
SP - 973
EP - 980
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 2
ER -