Visual evidence and quantification of interaction of polymeric sulfonylurea with pancreatic islet.
Using a polymeric sulfonylurea (PSU) designed from glibenclamide, we examined the interactions of sulfonylurea with pancreatic islets rather than genetically remodeled beta-cell lines to clarify the biological roles of ATP-sensitive K+ (KATP) channels to which sulfonylurea binds. PSU enhanced insulin secretion from the islets with 10 nM (SU equivalent) treatment, especially at low glucose concentration, but its activity was inhibited by 100 microM diazoxide. Confocal microscopy visualized PSU interactions with the islet and revealed that the modulation of intracellular Ca2+ occurred in the same region of an islet where PSU was also bound. In quantification method of the confocal microscopic images, competition of PSU with glibenclamide on its binding sites and glucose inhibition against PSU binding were confirmed. In this study, it was concluded that the PSU was a comparable drug with glibenclamide and offered a new standard method to study intact islets.
Kim
Sungwon
S
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, Suite 318, Salt Lake City, Utah 84108, USA. swk1@utah.edu
Bae
You Han
YH
D000818:Animals; D001667:Binding, Competitive; D020013:Calcium Signaling / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D018613:Microscopy, Confocal; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000737:chemistry / Q000494:pharmacology*
D007328:Insulin; D011108:Polymers; D013453:Sulfonylurea Compounds; D005947:Glucose; D005905:Glyburide