This study investigates the effects of gastric inhibitory polypeptide (GIP) and glycated GIP (glucitol adduct of GIP) on glucose uptake and metabolism in muscle. Glycated GIP (molecular mass 5147.2 Da) was purified by HPLC following in vitro incubation under hyperglycaemic reducing conditions (24 h at pH 7.4). GIP (10(-10)-10(-8) mol/l) significantly stimulated (1.4- to 1.5-fold, P < 0.001) 2-deoxy-D-[1-3H]glucose uptake in abdominal muscle pieces from 3- to 5-week-old lean mice compared with control incubations (without GIP). This stimulatory effect on glucose uptake at 10(-10)-10(-9) mol/l was decreased by 13-20% following glycation of the peptide (P < 0.05). GIP (10(-9) and 10(-8) mol/l) induced a stepwise 1.4- to 1.7-fold increase (P < 0.01, P < 0.001 respectively) in [14C]glucose oxidation compared with controls. This effect on glucose oxidation was diminished by 32% with 10(-8) mol/l glycated GIP (P < 0.05). GIP (10(-9) and 10(-8) mol/l) induced a 1.4- to 1.8-fold increase in [14C]glucose incorporation into muscle glycogen (glycogenesis) compared with controls. Glycated GIP (10(-8) mol/l) exhibited a 41% decrease in glycogenic activity (P < 0.01). GIP (10(-10)-10(-8) mol/l) stimulated lactate production in isolated abdominal muscle (1.2- to 1.3-fold, P < 0.05); however glycated GIP did not exert a significant effect. This study demonstrates for the first time that GIP promotes glucose uptake, glucose oxidation and glycogenesis in muscle tissue. Furthermore, modification of GIP through glycation diminishes its biological effectiveness.