Definitively, my cup of tea. Focus on 'Caffeine inhibits glucose transport by binding at the GLUT1 nucleotide-binding site'

摘要

caffeine and theophylline are the most widely ingested substances affecting behavior. Consumption is particularly high in Scandinavia at >400 mg per person per day; this is double that of the US or UK (5). A single cup of coffee raises plasma concentration to around 4 jxM. Caffeine acts as a nonspecific antagonist of brain interstitial fluid adeno-sine with G-type A and A2a adenosine receptors (IC50 ^ 5-10 ptM), thereby raising neural firing rates and brain metabolic rate. Caffeine also inhibits phosphodiesterase (IC50 ^ 0.5 mM) and triggers Ca2+ release from sarcoplas-mic reticulum (IC50 ^2-4 mM).Caffeine and theophylline inhibit glucose transport by direct action on the glucose transporter SLC2A1, GLUT1 (IC50 ^ 2-4 mM; Refs. 3 and 8), and they also inhibit insulin-dependent GLUT4 trafficking in adipocytes (IC50 ^ 250 (xM; Ref. 1).While concerns about xanthine-dependent inhibition of glucose uptake across the brain endothelial barrier may have been overstated (7), the likely stimulatory effects of normally ingested caffeine plausibly could, by depleting the compromised brain energy reserve in GLUT1 deficiency syndrome patients, exacerbate the tendency to epileptic seizures, as seen with exercise, or hunger (10).Although caffeine's inhibitory effects on glucose transport are not physiologically important, they usefully contribute to the still contentious debate regarding the mechanism of sugar transport.