GASTRIC-INHIBITORY POLYPEPTIDE AND EFFECTS OF GLYCATION ON GLUCOSE-TRANSPORT AND METABOLISM IN ISOLATED MOUSE ABDOMINAL MUSCLE

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 puri fied by HPLC following in vitro incubation under hyperglycaemic reduci ng conditions (24 h at pH 7.4). GIP (10(-10)-10(-8) mol/l) significant ly stimulated (1.4- to 1.5-fold, P<0.001) 2-deoxy-D-[1-H-3] glucose up take in abdominal muscle pieces from 3- to 5-week-old lean mice compar ed with control incubations (without GIP). This stimulatory effect on glucose uptake at 10(-10)-10(-9) mol/l was decreased by 13-20% followi ng glycation of the peptide (P<0.05). GIP (10(-9) and 10(-8) mol/l) in duced a stepwise 1.4- to 1.7-fold increase (P<0.01, P<0.001 respective ly) in [C-14]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 in crease in [C-14]glucose incorporation into muscle glycogen (glycogenes is) 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 eff ect. This study demonstrates for the first time that GIP promotes gluc ose uptake, glucose oxidation and glycogenesis in muscle tissue, Furth ermore, modification of GIP through glycation diminishes its biologica l effectiveness.