FAILURE OF LEPTIN TO AFFECT BASAL AND INSULIN-STIMULATED GLUCOSE-METABOLISM OF RAT SKELETAL-MUSCLE IN-VITRO

Studies on different isolated tissues have provided evidence that lept in may directly modulate cellular glucose handling. The present study was performed to elucidate leptin's action on basal and insulin-stimul ated glucose metabolism in native muscle tissue, which under physiolog ical circumstances is the quantitatively most important target tissue of insulin. Isolated rat soleus muscle strips were incubated for 1 h i n the absence or presence of leptin (0, 1, 10, or 100 nmol/l) under ba sal or insulin-stimulated conditions (10 nmol/l). No effects of leptin were found on the rates of H-3-2-deoxy-glucose transport (basal: cont rol, 314 +/- 14; 1 nmol/l leptin, 320 +/- 17; 10 nmol/l leptin, 314 +/ - 13; 100 nmol/l leptin, 322 +/- 16; insulin-stimulated: control, 690 +/- 33; 1 nmol/l leptin, 691 +/- 29; 10 nmol/l leptin, 665 +/- 26; 100 nmol/l leptin, 664 +/- 27; cpm.mg(-1).h(-1): NS vs respective control ) and on net glucose incorporation into glycogen (basal: control, 1.75 +/- 0.18; 1 nmol/l leptin, 2.01 +/- 0.13; 10 nmol/l leptin, 1.92 +/- 0.11; 100 nmol/l leptin, 1.81 +/- 0.13; insulin-stimulated: control, 5 .98 +/- 0.40; 1 nmol/l leptin, 5.93 +/- 0.30; 10 nmol/l leptin, 5.46 /- 0.25; 100 nmol/l leptin, 5.85 +/- 0.30; mu mol.g(-1).h(-1); NS vs r espective control). In parallel, leptin failed to affect rates of aero bic and anaerobic glycolysis as well as muscle glycogen content. Furth er experiments revealed that the inability of leptin to directly affec t muscle glucose handling prevailed independently of muscle fiber type (soleus and epitrochlear is muscle), of ambient insulin concentration s (0-30 nmol/l), and of leptin exposure time (1 h or 6 h). Thus, our f indings fail to support speculations about a physiological role of dir ect insulin-mimetic or insulin-desensitizing effects of leptin on skel etal muscle tissue.