Use Of Glibenclamide Research Articles

Long-term Follow-up of Gastroplasty in a Patient with Prader-Willi Syndrome.

To prevent the development of metabolic disturbances caused by overeating, we performed vertical banded gastroplasty in an adult woman with Prader-Willi syndrome. Her fasting blood sugar (FBS) and urinary sugar excretion (US) decreased during 6 months after the surgery under strict dietary control in the hospital. The insulin response to oral glucose at 6 months after surgery was as good as in the normal controls. A barium meal study in the 11th postoperative month revealed that the staple line was partially ruptured. After this, FBS and US increased, and the glucose tolerance and insulin response worsened. At 24 months, US was still less than preoperative US, and the oral glucose tolerance test showed a better result than before operation. At 29 months, her condition was brought under control with use of Glibenclamide. At 60 months, her FBS and US were at the same level as before operation. She was doing a part-time job. In conclusion, the effect of gastroplasty in preventing worsening of glucose metabolism in a case of Prader-Willi syndrome lasted satisfactorily for 24 months in spite of the partial breakdown of the staple line.

Pharmacological characterization of nicorandil by 86Rb efflux and isometric vasorelaxation studies in vascular smooth muscle.

Nicorandil and cromakalim were found to stimulate 86Rb efflux (a marker of K+ ions) from resting preparations of rabbit aorta. This action was suppressed by 10(-5) M glibenclamide, an antagonist of K(+)-channel openers in vascular smooth muscle. Through intracellular production of cyclic GMP, and subsequent suppression of cellular Ca2+ activation, nitrovasodilators interfere indirectly with the activation of Ca(2+)-dependent ion channels. 8-Bromo-cyclic GMP and sodium nitroprusside antagonized the Ca(2+)-dependent 86Rb efflux induced by 3 x 10(-7) M norepinephrine. When nicorandil and cromakalim were investigated in the same experimental setup in the presence of glibenclamide to suppress stimulation of K+ channels, only nicorandil also suppressed the norepinephrine-induced increase of the 86Rb efflux. These results confirm that nicorandil acts as both an opener of K+ channels and a nitrovasodilator. Nicorandil relaxed helical strips from rabbit aorta contracted by 10(-7) M norepinephrine, but in contrast to the relaxant action of cromakalim, this response was not antagonized by the use of glibenclamide, indicating a greater importance of the nitrovasodilator mechanism than of the K(+)-channel-opening activity for relaxation in this tissue. However, when the nitrate-like action of nicorandil was suppressed by 10(-5) M methylene blue, the K(+)-channel-opening activity was unmasked on addition of 10(-4) M glibenclamide at high concentrations of nicorandil.

Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP-sensitive potassium channel.

We investigated the contribution of opening of the ATP-sensitive K+ channel to extracellular accumulation of K+ during ischemia with the use of glibenclamide, a specific blocker of this K+ channel. To characterize the electrophysiological effects of glibenclamide during metabolic inhibition (by either application of dinitrophenol or hypoxia) we performed patch-clamp studies in isolated membrane patches of guinea pig myocytes and in intact guinea pig myocytes and studied action potential parameters in isolated superfused guinea pig papillary muscle. We studied the effect of glibenclamide on extracellular accumulation of K+ and H+ in isolated retrogradely perfused globally ischemic hearts of rat, guinea pig, and rabbit. Experimental evidence is presented that supports the conclusions that glibenclamide 1) effectively blocks open K+ATP channels, 2) reverses the dinitrophenol-induced increase of the outward current and prevents the hypoxia-induced shortening of the action potential, 3) decreases the rate of K+ accumulation during the first minutes of ischemia in stimulated hearts, an effect which was entirely absent in quiescent hearts, and 4) does not influence the rate and extent of ischemia-induced extracellular acidification.