Biomaterial Database

Ionic effects on the uptake of sulfonylurea (glibenclamide) by pancreatic islets. 1976

B Hellman, and J Sehlin, and I B Täljedal

The accumulation of glibenclamide was studied in the pancreatic islets of non-inbred ob/ob-mice. Microdissected islets were incubated in media of different ionic composition and the accumulation measured as the uptake of drug not accounted for by equilibration in the urea space. In 12 mM N-hydroxyethylpiperazine-N'-2-ethane sulphonic acid (HEPES) buffer the accumulation was only half of that in Krebs-Ringer bicarbonate buffer. Addition of 50 mM NaCl, Na2SO4, KCl, or LiCl to the HEPES buffer restored the accumulation to the level seen in Krebs-Ringer buffer. Studies with different concentrations of NaCl and Na2SO4 showed that the glibenclamide accumulation was sensitive to Na+ with little or no effect being attributable to the anions. CaCl2 or MgCl2 had much stronger effects than NaCl. It is concluded that cations participate in the binding of glibenclamide to beta-cells. The mechanism could be an increased ionic attraction between cell surfaces and hydrophilic regions of the drug, or a shielding of fixed surface anions allowing stronger hydrophobic interactions between drug and beta-cells.

UI	MeSH Term	Description	Entries
D007515	Islets of Langerhans	Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.	Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D008820	Mice, Obese	Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid.	Hyperglycemic Mice,Obese Mice,Mouse, Hyperglycemic,Mouse, Obese,Hyperglycemic Mouse,Mice, Hyperglycemic,Obese Mouse
D002414	Cations, Monovalent	Positively charged atoms, radicals or group of atoms with a valence of plus 1, which travel to the cathode or negative pole during electrolysis.	Monovalent Cation,Cation, Monovalent,Monovalent Cations
D005905	Glyburide	An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide	Glibenclamide,Daonil,Diabeta,Euglucon 5,Euglucon N,Glybenclamide,HB-419,HB-420,Maninil,Micronase,Neogluconin,HB 419,HB 420,HB419,HB420
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001692	Biological Transport	The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.	Transport, Biological,Biologic Transport,Transport, Biologic
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus