Characterization of the uptake of the methylxanthines theophylline and caffeine in isolated pancreatic islets and their effect on D-glucose transport.
The uptake of theophylline and caffeine was determined in isolated pancreatic islets employing a dual isotope procedure with sucrose as an extracellular marker. Islets rapidly accumulated caffeine and theophylline with apparent dissociation constants of approximately 23 and 6 mM, respectively. Theophylline inhibited the uptake of caffeine and caused displacement of caffein from islets. These results indicated a competition by theophylline and caffeine for a common site (binding and/or transport carrier). In addition, theophylline and caffeine inhibited D-glucose transport in a dose-dependent manner and within the limits of the experimental system, this inhibition appeared to be non-competitive. (Bu)2cAMP under similar experimental conditions exerted no effect on D-glucose transport. These results present evidence for a rapid uptake of theophylline and caffeine in pancreatic islets, which is compatible with their immediate cellular effects. In addition, these results demonstrate a direct effect by theophylline and caffeine on D-glucose transport which appears independent of their ability to alter intracellular cAMP levels.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002110:Caffeine / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D013806:Theophylline / Q000378:metabolism* / Q000494:pharmacology
D002110:Caffeine; D013806:Theophylline; D005947:Glucose