No deterioration of insulin secretion by the potassium channel opener pinacidil in essential hypertension.
Hypertension has been associated with hyperinsulinemia and insulin resistance. The elevations in plasma insulin are the apparent adaptation of the pancreatic beta cell to the resistance to insulin. Maintenance of normal insulin release is therefore of great importance for subjects with hypertension. The potassium channel opener pinacidil has antihypertensive properties. Pinacidil has been shown to inhibit Insulin release in vitro in isolated pancreatic beta cells. We therefore studied the acute effect of pinacidil on insulin secretion and insulin sensitivity in hypertensive and control subjects. The acute effect of pinacidil (25 mg, orally) on plasma insulin was studied during a hyperglycemic clamp (180 min, blood glucose 10 mmol/L) in 10 healthy volunteers and in 10 non-obese hypertensive patients in a randomised, placebo controlled double blind study. Fasting plasma insulin levels were 54.8 +/- 10.9 and 51.1 +/- 8.8 pmol/L in the control group and statistically significantly higher in the hypertensive group: 90.5 +/- 16.6 and 100.0 +/- 16.2 pmol/L (with and without pinacidil, respectively, both P < 0.02 vs control group). Plasma insulin levels rose to maximum levels of 246.7 +/- 44.6 and 267.2 +/- 56.2 pmol/L after 5 min in the control group (with and without pinacidil, respectively, NS) and to maximum levels of 248.9 +/- 37.3 and 238.0 +/- 39.1 pmol/L after 5 min in the hypertensive group (with and without pinacidil, respectively, NS). Areas under the insulin curve (AUCinsulin) of the first and second phase did not differ between the control and hypertensive group, with or without pinacidil. In the control and the hypertensive group separately no statistically significant effect of pinacidil on the mean glucose infusion rate/mean insulin level (M/I) ratio, a measure for insulin sensitivity, was shown. When both groups were taken together, an increase in the M/I ratio under the influence of pinacidil was found for the third hour of the clamp (P < 0.02). In conclusion, fasting insulin levels in the hypertensive subjects were significantly higher than in the control subjects. The potassium channel opener pinacidil did not influence insulin secretion in hypertensive patients and healthy controls. Pinacidil may have an enhancing effect on insulin sensitivity.
Ligtenberg
J J
JJ
Department of Endocrinology, Groningen University Hospital, The Netherlands.
Leenaers
A D
AD
Van Haeften
T W
TW
Smit
A J
AJ
Sluiter
W J
WJ
Reitsma
W D
WD
D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*
D006146:Guanidines; D007328:Insulin; D015221:Potassium Channels; D020110:Pinacidil