Lack of effect of the vasodilator pinacidil on insulin secretion in healthy humans.
Pinacidil is a new antihypertensive vasodilator drug which is supposed to act by opening of ATP-sensitive and glibenclamide-sensitive K+ channels in vascular smooth muscle cell membranes. Similar K+ channels play an important role in insulin secretion from pancreatic islets cells. Inhibition of insulin secretion has been demonstrated with high concentrations of pinacidil in vitro. In the present study the insulin response to oral glucose were studied in six healthy subjects before and on the last day of 2 weeks treatment with pinacidil. The drug was given by the oral route 12.5 mg bid in the first week and 25 mg bid in the second. There were no significant changes in fasting blood levels of insulin or glucose, glucose-stimulated insulin secretion, or oral glucose tolerance during pinacidil administration. These results may suggest that pinacidil at therapeutic concentrations does not activate insulin regulating K+ channels in pancreatic islet cells.
Department of Internal Medicine, Silkeborg General Hospital, Silkeborg, Denmark.
J E
JE
Nielsen-Kudsk
S
S
Mellemkjaer
C B
CB
Nielsen
C
C
Siggaard
D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005951:Glucose Tolerance Test; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D006146:Guanidines; D007328:Insulin; D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil