Sodium nitroprusside inhibits glucose-induced insulin release by activating ATP-sensitive K+ channels.
Sodium nitroprusside (SNP) has been reported to be a potent stimulator of cGMP formation in different tissues, including pancreatic islets. The present study aimed at comparing the effects of sodium nitroprusside and dibutyryl cGMP on 86Rb outflow, 45Ca outflow, short-term 45Ca uptake, cytosolic Ca2+ concentration and insulin release from rat pancreatic islet cells. The data indicate that cGMP potentiates whilst SNP inhibits the glucose-induced insulin release. This inhibitory effect appears to be mediated by the activation of ATP-sensitive K+ channels leading to a decrease in Ca2+ influx and subsequent reduction in cytosolic free Ca2+ concentration. Whatever the exact mechanism(s) underlying the capacity of sodium nitroprusside to enhance the K+ permeability of the B-cell membrane, the drug appears to be an inadequate pharmacological tool to characterize the involvement of cGMP in the insulin secretory process. The experimental results also suggest that cGMP potentiates glucose-induced insulin release without affecting ionic movements.
Antoine
M H
MH
Laboratory of Pharmacology, Free University of Brussels, School of Medicine, Belgium.
Hermann
M
M
Herchuelz
A
A
Lebrun
P
P
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D012413:Rubidium / Q000378:metabolism
D007328:Insulin; D015221:Potassium Channels; D009599:Nitroprusside; D003995:Dibutyryl Cyclic GMP; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D005947:Glucose; D012413:Rubidium; D002118:Calcium