Binding of sulphonylureas to plasma proteins - A KATP channel perspective.

PloS One
Peter ProksF M Ashcroft

Abstract

Sulphonylurea drugs stimulate insulin secretion from pancreatic β-cells primarily by inhibiting ATP sensitive potassium (KATP) channels in the β-cell membrane. The effective sulphonylurea concentration at its site of action is significantly attenuated by binding to serum albumin, which makes it difficult to compare in vitro and in vivo data. We therefore measured the ability of gliclazide and glibenclamide to inhibit KATP channels and stimulate insulin secretion in the presence of serum albumin. We used this data, together with estimates of free drug concentrations from binding studies, to predict the extent of sulphonylurea inhibition of KATP channels at therapeutic concentrations in vivo. KATP currents from mouse pancreatic β-cells and Xenopus oocytes were measured using the patch-clamp technique. Gliclazide and glibenclamide binding to human plasma were determined in spiked plasma samples using an ultrafiltration-mass spectrometry approach. Bovine serum albumin (60g/l) produced a mild, non-significant reduction of gliclazide block of KATP currents in pancreatic β-cells and Xenopus oocytes. In contrast, glibenclamide inhibition of recombinant KATP channels was dramatically suppressed by albumin (predicted free drug concentrat...Continue Reading

References

Jan 1, 1989·Progress in Biophysics and Molecular Biology·F M Ashcroft, P Rorsman
Apr 1, 1986·Diabetologia·J L CarpentierW J Malaisse
Oct 15, 1985·Clinica Chimica Acta; International Journal of Clinical Chemistry·T C Kwong
Apr 1, 1974·Journal of Pharmaceutical Sciences·P L HsuL A Luzzi
Sep 1, 1974·Metabolism: Clinical and Experimental·B Hellman
Nov 1, 1994·British Journal of Pharmacology·M SchwanstecherU Panten
Jul 1, 1996·Pflügers Archiv : European journal of physiology·A GomisM Valdeolmillos
May 22, 2002·Toxicology in Vitro : an International Journal Published in Association with BIBRA·H SeibertM Gülden
Dec 12, 2002·Diabetes·Peter ProksFrances Ashcroft
Jun 24, 2003·Diabetologia·F M Gribble, F Reimann
Oct 10, 2003·Clinical Pharmacology and Therapeutics·Ji-Young ParkJae-Gook Shin
Aug 10, 2005·Human Molecular Genetics·Peter ProksFrances M Ashcroft
Aug 4, 2006·The New England Journal of Medicine·Ewan R PearsonUNKNOWN Neonatal Diabetes International Collaborative Group
Nov 30, 2006·Diabetes·Jean-Claude HenquinMyriam Nenquin
Oct 11, 2008·Chemical Biology & Drug Design·Neelam Seedher, Mamta Kanojia
Aug 1, 2009·Science·Chang-Liang ZhangSusumu Seino
Sep 30, 2010·The Journal of General Physiology·Peter ProksFrances M Ashcroft
Dec 2, 2010·Nature Reviews. Drug Discovery·Dennis A SmithEdward H Kerns
Sep 20, 2011·Diabetes, Obesity & Metabolism·A S AbdelmoneimS H Simpson
Sep 29, 2011·American Journal of Physiology. Endocrinology and Metabolism·Nicolai M DolibaFranz M Matschinsky
Jul 31, 2013·Clinica Chimica Acta; International Journal of Clinical Chemistry·Jeanethe AnguizolaDavid S Hage
Aug 26, 2014·Nature Communications·Melissa F BreretonFrances M Ashcroft

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Citations

Jun 3, 2021·Journal of Personalized Medicine·Tanja DujicAida Kulo
May 18, 2020·Seminars in Cell & Developmental Biology·Piero MarchettiLorella Marselli

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