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We have examined the effects of streptozotocin (STZ)-induced diabetes (moderate and severe) on fatty acid transport and fatty acid transporter (FAT/CD36) and plasma membrane-bound fatty acid binding protein (FABPpm) expression, at the mRNA and protein level, as well as their plasmalemmal localization. These studies have shown that, with STZ-induced diabetes, 1) fatty acid transport across the plasma membrane is increased in heart, skeletal muscle, and adipose tissue and is reduced in liver; 2) changes in fatty acid transport are generally not associated with changes in fatty acid transporter mRNAs, except in the heart; 3) increases in fatty acid transport in heart and skeletal muscle occurred with concomitant increases in plasma membrane FAT/CD36, whereas in contrast, the increase and decrease in fatty acid transport in adipose tissue and liver, respectively, were accompanied by concomitant increments and reductions in plasma membrane FABPpm; and finally, 4) the increases in plasma membrane transporters (FAT/CD36 in heart and skeletal muscle; FABPpm in adipose tissue) were attributable to their increased expression, whereas in liver, the reduced plasma membrane FABPpm appeared to be due to its relocation within the cell in the face of slightly increased expression. Taken together, STZ-induced changes in fatty acid uptake demonstrate a complex and tissue-specific pattern, involving different fatty acid transporters in different tissues, in combination with different underlying mechanisms to alter their surface abundance. fatty acid transporter CD6; plasma membrane-bound fatty acid binding protein; muscle; heart; liver; adipose tissue

Rates of lactate uptake into giant sarcolemmal vesicles were determined in vesicles collected from rat muscles at rest and immediately after 10 min of intense muscle contraction. This contraction period reduced muscle glycogen rapidly by 37-82% in all muscles examined (P < 0.05) except the soleus muscle (no change P > 0.05). At an external lactate concentration of 1 mM lactate, uptake into giant sarcolemmal vesicles was not altered (P > 0.05), whereas at an external lactate concentration of 20 mM, the rate of lactate uptake was increased by 64% (P < 0.05). Concomitantly, the plasma membrane content of monocarboxylate transporter (MCT)1 was reduced slightly (-10%, P < 0.05), and the plasma membrane content of MCT4 was reduced further (-25%, P < 0.05). In additional studies, the 10-min contraction period increased the plasma membrane GLUT4 (P < 0.05) while again reducing MCT4 (-20%, P < 0.05) but not MCT1 (P > 0.05). These studies have shown that intense muscle contraction can increase the initial rates of lactate uptake, but only when the external lactate concentrations are high (20 mM). We speculate that muscle contraction increases the intrinsic activity of the plasma membrane MCTs, because the increase in lactate uptake occurred while plasma membrane MCT4 was decreased and plasma membrane MCT1 was reduced only minimally, or not at all. lactate transport; GLUT4; giant vesicles

Leptin acutely increases fatty acid (FA) oxidation and triacylglycerol (TG) hydrolysis and decreases TG esterification in oxidative rodent muscle. However, the effects of chronic leptin administration on FA metabolism in skeletal muscle have not been examined. We hypothesized that chronic leptin treatment would enhance TG hydrolysis as well as the capacity to oxidize FA in soleus (SOL) muscle. Female Sprague-Dawley rats were infused for 2 wk with leptin (LEPT; 0.5 mg*[kg.sup.-1]*[day.sup.-1]) by use of subcutaneously implanted miniosmotic pumps. Control (AD-S) and pair-fed (PF-S) animals received saline-filled implants. Subsequently, FA metabolism was monitored for 45 min in isolated, resting, and contracting (20 tetani/min) SOL muscles by means of pulse-chase procedures. Food intake (-33 [+ or -] 2%, P < 0.01) and body mass (-12.5 [+ or -] 4%, P = 0.01) were reduced in both LEPT and PF-S animals. Leptin levels were elevated (+418 [+ or -] 7%, P < 0.001) in treated animals but reduced in PF-S animals (-73 [+ or -] 8%, P < 0.05) relative to controls. At rest, TG hydrolysis was increased in leptin-treated rats (1.8 [+ or -] 2.2, AD-S vs. 23.5 [+ or -] 8.1 nmol/g wet wt, LEPT; P < 0.001). In contracting SOL muscles, TG hydrolysis (1.5 [+ or -] 0.6, AD-S vs. 3.6 [+ or -] 1.0 [micro]mol/g wet wt, LEPT; P = 0.02) and palmitate oxidation (18.3 [+ or -] 6.7, AD-S vs. 45.7 [+ or -] 9.9 nmol/g wet wt, LEPT; P < 0.05) were both significantly increased by leptin treatment. Chronic leptin treatment had no effect on TG esterification either at rest or during contraction. Markers of overall (citrate synthase) and FA (hydroxyacyl-CoA dehydrogenase) oxidative capacity were unchanged with leptin treatment. Protein expression of hormone-sensitive lipase (HSL) was also unaltered following leptin treatment. Thus leptin-induced increases in lipolysis are likely due to HSL activation (i.e., phosphorylation). Increased FA oxidation secondary to chronic leptin treatment is not due to an enhanced oxidative capacity and may be a result of enhanced flux into the mitochondrion (i.e., carnitine palmitoyltransferase I regulation) or electron transport uncoupling (i.e., uncoupling protein-3 expression). pulse chase; hormone-sensitive lipase; citrate synthase; [beta]-hydroxyacyl-coenzyme A dehydrogenase

Insulin induces the translocation of the fatty acid transporter FAT/CD36 to the plasma membrane. Am J Physiol Endocrinol Metab 282: E491-E495, 2002; 10.1152/ajpendo.00419.2001.--It is well known that muscle contraction and insulin can independently translocate GLUT-4 from an intracellular depot to the plasma membrane. Recently, we have shown that the fatty acid transporter FAT/CD36 is translocated from an intracellular depot to the plasma membrane by muscle contraction ( hindlimb perfusion; glucose transporter 4; palmitate; oxidation; triacylglycerol; diacylglycerol; phospholipids

A study was conducted to determine the effects of the rise of oxidate capacity of skeletal muscle to fatty acid (FA) uptake, FA transporter expression and FA metabolism. Results of experiments with male Sprague-Dawley rats indicate that the increase in muscle contractile activity through chronic electrical simulation has a parallel effect to fatty acid metabolism and transport. It was also observed that the rise of oxidate capacity of skeletal muscles steps up the expression of the membrane transporter FAT/CD36.

Dietary fatty acid composition of a high-fat (HF) diet influences the tissue-specific insulin resistance and systemic glucose tolerance in rats. Consistent body weights were observed in the rats belonging to the different dietary groups. However, insulin resistance varied among the rat groups highlighting the need for evaluating HF dietary effects on insulin and glucose metabolism and the requirements of tissue-specific glucose homeostasis.

A study showed that the effects of epinephrine on lipid metabolism in resting skeletal muscle depend on the physiological levels of epinephrine. The finding is based on experiments performed on incubated rat muscles that were pulsed with [1-14C]palmitate and chased with [9,10-3H] palmitate. The epitrochlearis, flexor digitorum brevis and soleus muscles were considered to reflect the range of oxidative capacities. The Western blotting method was used to characterize the muscle lipid hydrolysis potential and to measure total hormone-sensitive lipase content.

Glucose uptake and glucose transporter translocation was investigated in perfused isolated rat muscles in the presence of epinephrine and insulin, alone or in combination. Both epinephrine and insulin enhance glucose uptake and increase transporter translocation. When the two are given in combination, epinephrine antagonizes the glucose uptake induced by insulin but not transporter translocation.

Electrical stimulation induces GLUT-4 translocation to the plasma membrane and transverse tubules of red gastrocnemius (RG) and white gastrocnemius (WG) muscles. Experiments were conducted testing the hypothesis that GLUT-4 translocation to the cell surface may underlie the responsiveness of type II muscle fibers. The greater translocation of GLUT-4 to transverse tubules of WG in contrast to RG may provide an explanation on both muscle types' responsiveness toward supramaximal electrical stimulation.

Research was conducted to examine whether chronic stimulation of red and white rat muscles increased the concentrations of the monocarboxylate transporter MCT1. Red and white tibialis anterior (RTA and WTA, respectively) and extensor digitorum longus (EDL) muscles were chronically stimulated via the peroneal nerve for 7 days. Stimulated and contralateral muscles were analyzed for MCTI content, L-lactate uptake, lactate dehydrogenase (LDH) isoforms and muscle fiber composition. Results show that chronic muscle contraction increases MCT1 in white and red skeletal muscles.

Expression of the glucose transporter isoforms, GLUT-1 and GLUT-4, has no effect on insulin-mediated glucose transport into cells. In a study of rats, chronic stimulation of skeletal muscles overexpressing the GLUT-1 gene but not GLUT-4 stimulated the transport of 2-deoxy-D-glucose. Similar results were observed in muscles overexpressing the GLUT-4 gene only. The greatest increases were observed in the white muscles. Meanwhile, muscles overexpressing both GLUT-1 and GLUT-4 did not impair muscle contraction, suggesting that increases in basal glucose transport have no effect on muscle glucose transport.

The skeletal muscles are the major site of lactate formation. Transport of lactate in and out of these muscles are carried out by lactate transporters such as the monocarboxylate transporter (MCT1). To characterize MCT1, an antibody was constructed against the MCT1 protein and was analyzed for its expression. Results showed higher MCT1 expression in red than in white muscles. Expression was correlated with oxidative fiber content and lactate uptake by the muscles. Lactate dehydrogenase activity in the heart was also closely correlated with MCT1, suggesting that MCT1 may be expressed with heart forms of LDH.

Subjects maintained on short-term exercise had small increases in the number of glucose transporter (GLUT) proteins in the skeletal muscle. In contrast, endurance training produced immediate and progressive increases in GLUT-4. Increases in GLUT-1 were also observed, but only after 31 days of training. Increases in muscle hexokinase (HK) activity were evident after five days of training, but muscle malate dehydrogenase only increased 31 days after training. These results suggest that changes in GLUT-4 and HK were induced during early exercise.