Effects of analogues of adenosine and methyl xanthines on insulin sensitivity in soleus muscle of the rat

Abstract

The concentration of insulin that produces half‐maximal stimulation of glycolysis by stripped soleus muscle preparations is markedly increased by the adenosine analogues, 2‐chloroadenosine and N 6‐phenylisopropyladenosine, but is markedly decreased by the methyl xanthine analogue, 8‐phenyltheophylline. 2‐Chloroadenosine increases the concentration of insulin required to stimulate glycolysis half maximally, from about 100 to 2000 μunits/ml. 8‐Phenyltheophylline decreases this concentration of insulin from about 100 to 10 μunits/ml, an effect which is similar to that produced either by addition of adenosine deaminase to the medium or to exercise‐training of the donor animals for 4 weeks.

Activation of the A1adenosine receptor increases insulin-stimulated glucose transport in isolated rat soleus muscle

“…Our results showing that activation of the A 1 adenosine receptor increases while A 1 adenosine receptor antagonism is without effect on insulin-stimulated glucose transport is congruent with Han et al (1998), but not with Budohoski et al (1984), Challiss et al (1992), Espinal et al (1983), or Hashimoto et al (1987. Similarly, our results showing that adenosine modulation of glucose transport facilitated by insulin contributes to insulin sensitivity but not to responsiveness are also compatible with most (Challiss et al 1992; Fig.…”

“…Dagger ({) indicates p < 0.05 vs. insulin alone. Budohoski et al 1984;Heseltine et al 1995;Kuroda et al 1987), but not all (Han et al 1998), studies. One possibility for these discrepancies might be related to the concentrations of insulin and (or) the pharmacological agents employed.…”

“…In adipose tissue, adenosine is also a potent antilipolytic agent (Heseltine et al 1995;van Schaick et al 1998). However, in rodent skeletal muscle, the acute effects of adenosine on insulin action have been equivocal, with reports of no effect (Vergauwen et al 1994), as well as stimulatory (Han et al 1998) and inhibitory (Budohoski et al 1984;Challiss et al 1992;Espinal et al 1983) effects, on insulinstimulated glucose transport. Similarly, there is also disagreement as to whether the presence of insulin is necessary for adenosine to elicit an effect on glucose transport in contracting muscle (Vergauwen et al 1994;Derave and Hespel 1999).…”

Adenosine, Adenosine Receptors and Their Role in Glucose Homeostasis and Lipid Metabolism

“…Insulin activation in muscle tissue is not only associated with inhibition of glycolysis but with transport of glucose and activation of glycogen synthesis. Reports show that adenosine had an effect on only glycolysis (Espinal et al, 1983; Budohoski et al, 1984; Challis et al, 1984) and glucose transport by stimulation of the insulin sensitive glucose transporters GLUT4 (Vannucci et al, 1992); glycogen synthesis was not affected by adenosine (Challis et al, 1984). In isolated soleus muscles from rats, it was found that depletion of adenosine (by adenosine deaminase) in the surrounding media improved insulin sensitivity.…”

“…The observed effect on insulin sensitivity was due to decrease in the concentration of insulin necessary to activate glycolysis (Espinal et al, 1983). Using the same model and adenosine analogs, reduction in insulin sensitivity was observed when insulin levels were reduced to half of the maximum dose required to stimulate glycolysis in the muscle (Budohoski et al, 1984). Non‐specific adenosine receptor antagonists (methyl xanthines) reversed the inhibitory effect of adenosine on insulin signaling (Budohoski et al, 1984).…”