EFFECTS OF METFORMIN TREATMENT ON GLUCOSE-TRANSPORTER PROTEINS IN SUBCELLULAR-FRACTIONS OF SKELETAL-MUSCLE IN (FA FA) ZUCKER RATS/

1 The present study was designed to clarify the cellular mechanism thr ough which the antihyperglycaemic drug, metformin, exerts its effects. For this purpose the contents of glucose transporter protein isoforms GLUT1 and GLUT4 were measured in plasma membrane and intracellular me mbrane fractions of skeletal muscle obtained from genetically obese, i nsulin-resistant Zucker rats. 2 Hindlimb muscles were dissected from m etformin-treated (300 mg kg(-1) day(-1), p.o., for 12 days) and contro l rats in basal treatment state, and after acute stimulation with insu lin (22 u kg(-1), i.p.). Since metformin treatment reduces food intake , we also used a pair-fed control group to investigate the effects of altered insulinaemia per se. Glucose transporter levels were analysed by Western blot and slot blot-techniques. In addition, 2-deoxy-[C-14]- glucose uptake in isolated muscle strips was evaluated. 3 No changes w ere noted in the contents of GLUT1 proteins in any of the subcellular fractions after metformin treatment. The contents of GLUT4 in subcellu lar fractions were not altered in the basal treatment state. After acu te insulin exposure the content of GLUT4 in the intracellular membrane fraction declined significantly in the metformin-treated group, while no significant effect was seen in the plasma membrane fraction. In ag reement with these results, metformin treatment did not alter 2-deoxyg lucose uptake into isolated muscle strips.4 In conclusion, the present study does not support the concept that metformin would enhance trans location of glucose transporter proteins from the intracellular compar tment to the plasma membrane in skeletal muscle in vivo.