Adenosine receptors mediate synergistic stimulation of glucose uptake and transport by insulin and by contractions in rat skeletal muscle.

Abstract

The role of adenosine receptors in the regulation of muscle glucose uptake by insulin and contractions was studied in isolated rat hindquarters that were perfused with a standard medium containing no insulin or a submaximal concentration of 100 gU/ml. Adenosine receptor antagonism was induced by caffeine or 8-cyclopentyl-1,3-dipropylxantine (CPDPX). Glucose uptake and transport were measured before and during 30 min of electrically induced muscle contractions. Caffeine nor CPDPX affected glucose uptake in resting hindquarters. In contrast, the contraction-induced increase in muscle glucose uptake was inhibited by 30-50% by caffeine, as well as by CPDPX, resulting in a 20-25% decrease in the absolute rate of glucose uptake during contractions, compared with control values. This inhibition was independent of the rate of perfusate flow and only occurred in hindquarters perfused with insulin added to the medium. Thus, adenosine receptor antagonism inhibited glucose uptake during simultaneous exposure to insulin and contractions only. Accordingly, caffeine inhibited 3-0-methylglucose uptake during contractions only in oxidative muscle fibers that are characterized by a high sensitivity to insulin. In conclusion, the present data demonstrate Al receptors to regulate insulin-mediated glucose transport in contracting skeletal muscle. The findings provide evidence that stimulation of sarcolemmic adenosine receptors during contractions is involved in the synergistic stimulation of muscle glucose transport by insulin and by contractions. (J. Clin. Invest. 1994. 93:974-981.)

Acute non‐insulin‐like stimulation of rat muscle glucose metabolism by troglitazone in vitro

“…synergy, we also compared the incremental e ects induced by hypoxia or by 3250 nmol l 71 troglitazone at di erent ambient insulin concentrations. In parallel to described synergic stimulation of muscle glucose uptake by insulin and muscle contractions (DeFronzo et al, 1981;Vergauwen et al, 1994), our ®ndings clearly indicate synergy of insulin and hypoxia, which goes beyond conclusions drawn from previous studies demonstrating only additivity (Cartee et al, 1991;Azevedo et al, 1995; FuÈ rnsinn et al , 1996). The troglitazone-dependent shift of intracellular glucose¯ux into glycolysis rather than glycogenesis was found to persist independently of prevailing insulin stimulation and a considerably higher troglitazone-induced increment in glucose transport was observed in the presence than in the absence of 5 nmol l 71 insulin (P50.005 by Student's t test).…”

Caffeine-Induced Impairment of Insulin Action but Not Insulin Signaling in Human Skeletal Muscle Is Reduced by Exercise

“…In rat adipocytes (20) and in the perfused contracting rat hindlimb (21), methylxanthines inhibited insulin-stimulated glucose uptake, and this inhibitory action was attributed to the antagonistic effects of methylxanthine on the A 1 adenosine receptor. We have previously shown that caffeine administration at doses eliciting plasma concentrations equivalent to concentrations obtainable after drinking 3-4 cups of coffee (19) decreased whole-body insulin sensitivity in sedentary males (22).…”

Caffeine Can Decrease Insulin Sensitivity in Humans

“…Some studies have reported adenosine to increase insulin-mediated glucose metabolism in adipose tissue (5,31) and to decrease metabolism in skeletal muscle (32). Others have recorded decreased skeletal muscle glucose uptake with degradation or blocking of adenosine (33,34), indicating uniform effects of adenosine on (insulin-mediated) glucose metabolism in fat and muscle. In obese Zucker rats, blocking peripheral interstitial adenosine by systemic administration of a methylxanthine not entering the brain increased whole-body (insulinmediated) glucose uptake, thus improving glucose tolerance (4).…”