TY - JOUR
T1 - Imidazoline compounds stimulate insulin release by inhibition of K(ATP) channels and interaction with the exocytotic machinery
AU - Zaitsev, Sergei V.
AU - Efanov, Alexandre M.
AU - Efanova, Ioulia B.
AU - Larsson, Olof
AU - Östenson, Claes Göran
AU - Gold, Gerald
AU - Berggren, Per Olof
AU - Efendić, Suad
PY - 1996/1/1
Y1 - 1996/1/1
N2 - A novel imidazoline compound, RX671024, was used to investigate the mechanisms by which imidazoline derivatives promote insulin secretion in rat pancreatic β-cells and HIT T15 cells. RX871024 stimulated insulin release from rat pancreatic β-cells and HIT T15 cells in a glucose-dependent way. This effect was not related to α2-adrenergic, I1-, and I2-imidazoline receptors. RX871024 promoted insulin release by at least two modes of action. One included an increase in cytoplasmic free Ca2+ concentration ([Ca2+](i)), subsequent to blocking of ATP-dependent K+ channels, membrane depolarization, and activation of voltage-dependent Ca2+ channels. The other, a more distal effect of imidazoline, affected the exocytotic machinery and was unrelated to changes in membrane potential and [Ca2+](i). The mechanism of RX871024-induced insulin release was dependent on protein kinases A and C. The sensitizing effect of a low dose of RX871024 on glucose- induced insulin secretion suggests that imidazoline compounds of this kind may constitute the basis for development of a new class of oral hypoglycemic agents.
AB - A novel imidazoline compound, RX671024, was used to investigate the mechanisms by which imidazoline derivatives promote insulin secretion in rat pancreatic β-cells and HIT T15 cells. RX871024 stimulated insulin release from rat pancreatic β-cells and HIT T15 cells in a glucose-dependent way. This effect was not related to α2-adrenergic, I1-, and I2-imidazoline receptors. RX871024 promoted insulin release by at least two modes of action. One included an increase in cytoplasmic free Ca2+ concentration ([Ca2+](i)), subsequent to blocking of ATP-dependent K+ channels, membrane depolarization, and activation of voltage-dependent Ca2+ channels. The other, a more distal effect of imidazoline, affected the exocytotic machinery and was unrelated to changes in membrane potential and [Ca2+](i). The mechanism of RX871024-induced insulin release was dependent on protein kinases A and C. The sensitizing effect of a low dose of RX871024 on glucose- induced insulin secretion suggests that imidazoline compounds of this kind may constitute the basis for development of a new class of oral hypoglycemic agents.
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U2 - 10.2337/diab.45.11.1610
DO - 10.2337/diab.45.11.1610
M3 - Article
C2 - 8866568
AN - SCOPUS:0029973985
VL - 45
SP - 1610
EP - 1618
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 11
ER -