Abstract
Effects of the α2-adrenergic agonist clonidine on insulin release, membrane potential, and cytoplasmic free Ca2+ concentration ([Ca2+](i)) were investigated using pancreatic β-cells isolated from obese hyperglycemic mice. Addition of 2 μM clonidine promptly inhibited glucose-stimulated insulin release, an effect accompanied by a lowering in both membrane potential and [Ca2+](i). Within minutes, the effect on Ca2+ was partly reversed, [Ca2+](i) attaining a new level, although still significantly lower than in the absence of agonist. This late increase in [Ca2+](i) was inhibited by 50 μM D-600, a blocker of voltage-activated Ca2+ channels. The inhibitory effects of clonidine on membrane potential, [Ca2+](i), and insulin release were abolished by 5 μM of the α2-adrenergic antagonist yohimbine. Depolarization with high K+ increased [Ca2+](i) also in the presence of clonidine, conditions accompanied by only a minute release of insulin. Secretion was, however, partly restored by subsequent addition of 20 mM glucose. Addition of 5 mM Ca2+ transiently reversed the effects of clonidine on both membrane potential and [Ca2+](i). Although the clonidine-induced repolarization should be enough for closing the voltage-activated Ca2+ channels with a resulting decrease in [Ca2+](i), a direct interaction of the agonist with these channels cannot be excluded. The fact that it was possible to increase [Ca2+](i) with only a minor effect on insulin release suggests that the inhibitory effect of clonidine not only is due to a reduction in [Ca2+](i), but also involves interference with some more distal step in the insulin secretory machinery.
| Original language | English |
|---|---|
| Pages (from-to) | 1855-1860 |
| Number of pages | 6 |
| Journal | Journal of Biological Chemistry |
| Volume | 263 |
| Issue number | 4 |
| State | Published - Jan 1 1988 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Inhibition of glucose-stimulated insulin release by α2-adrenoceptor activation is parallelled by both a repolarization and a reduction in cytoplasmic free Ca2+ concentration. / Nilsson, T.; Arkhammar, P.; Rorsman, P.; Berggren, P. O.
In: Journal of Biological Chemistry, Vol. 263, No. 4, 01.01.1988, p. 1855-1860.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of glucose-stimulated insulin release by α2-adrenoceptor activation is parallelled by both a repolarization and a reduction in cytoplasmic free Ca2+ concentration
AU - Nilsson, T.
AU - Arkhammar, P.
AU - Rorsman, P.
AU - Berggren, P. O.
PY - 1988/1/1
Y1 - 1988/1/1
N2 - Effects of the α2-adrenergic agonist clonidine on insulin release, membrane potential, and cytoplasmic free Ca2+ concentration ([Ca2+](i)) were investigated using pancreatic β-cells isolated from obese hyperglycemic mice. Addition of 2 μM clonidine promptly inhibited glucose-stimulated insulin release, an effect accompanied by a lowering in both membrane potential and [Ca2+](i). Within minutes, the effect on Ca2+ was partly reversed, [Ca2+](i) attaining a new level, although still significantly lower than in the absence of agonist. This late increase in [Ca2+](i) was inhibited by 50 μM D-600, a blocker of voltage-activated Ca2+ channels. The inhibitory effects of clonidine on membrane potential, [Ca2+](i), and insulin release were abolished by 5 μM of the α2-adrenergic antagonist yohimbine. Depolarization with high K+ increased [Ca2+](i) also in the presence of clonidine, conditions accompanied by only a minute release of insulin. Secretion was, however, partly restored by subsequent addition of 20 mM glucose. Addition of 5 mM Ca2+ transiently reversed the effects of clonidine on both membrane potential and [Ca2+](i). Although the clonidine-induced repolarization should be enough for closing the voltage-activated Ca2+ channels with a resulting decrease in [Ca2+](i), a direct interaction of the agonist with these channels cannot be excluded. The fact that it was possible to increase [Ca2+](i) with only a minor effect on insulin release suggests that the inhibitory effect of clonidine not only is due to a reduction in [Ca2+](i), but also involves interference with some more distal step in the insulin secretory machinery.
AB - Effects of the α2-adrenergic agonist clonidine on insulin release, membrane potential, and cytoplasmic free Ca2+ concentration ([Ca2+](i)) were investigated using pancreatic β-cells isolated from obese hyperglycemic mice. Addition of 2 μM clonidine promptly inhibited glucose-stimulated insulin release, an effect accompanied by a lowering in both membrane potential and [Ca2+](i). Within minutes, the effect on Ca2+ was partly reversed, [Ca2+](i) attaining a new level, although still significantly lower than in the absence of agonist. This late increase in [Ca2+](i) was inhibited by 50 μM D-600, a blocker of voltage-activated Ca2+ channels. The inhibitory effects of clonidine on membrane potential, [Ca2+](i), and insulin release were abolished by 5 μM of the α2-adrenergic antagonist yohimbine. Depolarization with high K+ increased [Ca2+](i) also in the presence of clonidine, conditions accompanied by only a minute release of insulin. Secretion was, however, partly restored by subsequent addition of 20 mM glucose. Addition of 5 mM Ca2+ transiently reversed the effects of clonidine on both membrane potential and [Ca2+](i). Although the clonidine-induced repolarization should be enough for closing the voltage-activated Ca2+ channels with a resulting decrease in [Ca2+](i), a direct interaction of the agonist with these channels cannot be excluded. The fact that it was possible to increase [Ca2+](i) with only a minor effect on insulin release suggests that the inhibitory effect of clonidine not only is due to a reduction in [Ca2+](i), but also involves interference with some more distal step in the insulin secretory machinery.
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UR - http://www.scopus.com/inward/citedby.url?scp=0023905926&partnerID=8YFLogxK
M3 - Article
C2 - 2892833
AN - SCOPUS:0023905926
VL - 263
SP - 1855
EP - 1860
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 4
ER -