The decreased sensitivity of glycolysis to insulin seen in isolated soleus muscles from genetically obese Zucker rats was abolished by addition of the adenosine-receptor antagonist 8-phenyltheophylline to the incubation medium; 8-phenyltheophylline had no effect on the sensitivity of glycogen synthesis to insulin. These findings suggest that changes in the sensitivity of glucose utilization by muscles of genetically obese rats may be explained, in part, by a modification in either the concentration of adenosine or the affinity of adenosine receptors in skeletal muscle.
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.
Starvation decreases activities of some glycolytic and citric acid-cycle enzymes, and increases those of glucose 6-phosphatase and fructose bisphosphatase, whereas that of glutaminase is unchanged. These findings may be of significance for the control of glucose metabolism in the absorptive cells of the intestine.
The effects of cold-exposure, the hyperthyroid state and a single exercise bout in vivo on the maximal enzyme activities of 6-phosphofructokinase and fructose-1,6-bisphosphatase in vastus lateralis muscle and the rates of fructose 6-phosphate/fructose 1,6-bisphosphate cycling measured in epitrochlearis muscle in vitro were investigated. In all cases significant changes in substrate cycling rates were observed, whether in the absence of added hormones in vitro (acute exercise), or when stimulated by insulin plus adrenaline (cold-exposure), or with respect to the catecholamine-sensitivity of the cycling rate (the hyperthyroid state).
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