@article{oai:hirosaki.repo.nii.ac.jp:00003628,
 author = {Wakui, Makoto and Misaki, Naoko and Suga, Sechiko and Mao, Xia and Lin, Yu-Fung and Wu, Jie},
 issue = {Supplement},
 journal = {弘前医学},
 month = {Nov},
 note = {application/pdf, Diabetes mellitus is a group of diseases characterized by high levels of blood glucose resulting from defects
in insulin production, insulin action, or both. Diabetes patients usually have accompanying cardiovascular disorders.
Sulfonylureas have been the leading oral antihyperglycemic agents for type 2 diabetes treatment, which currently still
constitute the most popular anti-diabetic drugs. Nevertheless, concern has arisen over the side eff ects of sulfonylureas
on the cardiovascular system. Here we report that iptakalim, a novel cardiovascular ATP-sensitive potassium（ KATP）
channel opener, closed rat pancreatic β-cell KATP channels and increased insulin release. Using whole-cell patch-clamp
recordings, iptakalim depolarized β-cells, induced action potential fi ring and reduced pancreatic KATP channel currents.
Using single-channel recordings, iptakalim reduced KATP channel open-probability independently of intracellular ATP
concentrations. We demonstrated that iptakalim elevated intracellular Ca2+ concentrations and increased insulin release as
revealed by fl uorescence imaging（ fura-2） and biochemical measurements, respectively. In addition, iptakalim signifi cantly
inhibited the open-probability of recombinant Kir6.2/SUR1 and Kir6.2FL4A（ a traffi cking mutant of the Kir6.2） channels
expressed in transfected human embryonic kidney （HEK） 293 cells. Collectively, iptakalim, a cardiovascular KATP
channel opener, closes rat pancreatic β-cell KATP channels, which may result from direct inhibition of the Kir6.2 subunit.
Therefore, iptakalim bi-directionally regulates KATP channels in cardiovascular and pancreatic tissues, and this unique
pharmacological property suggests iptakalim could be used as a new therapeutic strategy for the treatment of type 2
diabetes with the potential benefi t in alleviating cardiac and/or vascular disorders frequently associated with diabetes., 弘前医学. 59(Suppl.), 2007, p.S89-S100},
 pages = {S89--S100},
 title = {Closure by iptakalim, a cardiovascular KATP channel opener, of rat pancreatic β-cell KATP channels and its molecular basis},
 volume = {59},
 year = {2007}
}