Failure of leptin to affect basal and insulin-stimulated glucose metabolism of rat skeletal muscle in vitro

Abstract

Studies on different isolated tissues have provided evidence that leptin may directly modulate cellular glucose handling. The present study was performed to elucidate leptin's action on basal and insulin-stimulated glucose metabolism in native muscle tissue, which under physiological circumstances is the quantitatively most important target tissue of insulin. Isolated rat soleus muscle strips were incubated for 1 h in the absence or presence of leptin (0, 1, 10, or 100 nmol/l) under basal or insulin- stimulated conditions (10 nmol/l). No effects of leptin were found on the rates of 3H-2-deoxy-glucose transport (basal: control, 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/1 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; insulinstimulated: 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; μmol · g-1 · h-1; NS vs respective control). In parallel, leptin failed to affect rates of aerobic and anaerobic glycolysis as well as muscle glycogen content. Further experiments revealed that the inability of leptin to directly affect muscle glucose handling prevailed independently of muscle fiber type (soleus and epitrochlearis muscle), of ambient insulin concentrations (0-30 nmol/l), and of leptin exposure time (1 h or 6 h). Thus, our findings fail to support speculations about a physiological role of direct insulin-mimetic or insulin-desensitizing effects of leptin on skeletal muscle tissue.