The adenosine kinase inhibitor 5-iodotubercidin (Itu) was found to have the following effects on glycogen metabolism in hepatocytes of fasted rats. (1) Itu strongly stimulated glycogen synthesis from different substrates (glucose, lactate plus pyruvate, dihydroxyacetone, glycerol and fructose). In cells incubated with these substrates, the well-known stimulating effect of amino acids and that of Itu was more than additive. (2) In parallel with the increase in glycogen deposition, there was an increase in synthase a and a decrease in phosphorylase a concentrations after administration of Itu. Synthase a was increased by Itu and amino acids in an additive manner, whereas the observed activation of phosphorylase after addition of amino acids was antagonized by Itu. (3) In contrast with amino acids, Itu increased neither the cell volume nor the aspartate and glutamate concentrations. (4) Itu enhanced the levels of cyclic AMP. The stimulation of glycogen deposition in the presence of Itu persisted when the cyclic AMP concentration was further increased by adenosine or 2-chloroadenosine. (5) Itu decreased the concentration of ATP, but its effects on glycogen synthesis, synthase a and phosphorylase a concentrations persisted when the ATP catabolism was prevented by adenosine. (6) The effect of Itu on glycogen synthesis was not the result of inhibition of adenosine kinase, since 5′-amino-5′-deoxyadenosine, another inhibitor of this enzyme, had no effect on glycogen deposition.

5-Iodotubercidin (Itu) and proglycosyn (Pro) have similar glycogenic properties. To compare their mechanisms of action, we tested them in hepatocytes from fasted rats. We show that both compounds are similar in that they stimulated glycogen synthesis, increased the concentration of synthase a, decreased that of phosphorylase a and lowered the concentration of F-2,6-P2 in the presence of glucose, lactate-pyruvate and amino acids. However, when amino acids were absent, Pro was the better stimulator of glycogenesis than Itu and in combination they elevated glycogen and synthase a concentrations synergistically. Further they differ in that (1) Itu enhanced the levels of cyclic AMP whereas Pro did not; (2) Pro depressed glucose production from gluconeogenic substrates, whereas Itu stimulated this process; (3) the inhibition of F-2,6-P2 formation and glycolysis by Pro became much weaker than that by Itu when glucose concentrations were raised from 10 to 20 mM. Inhibition of glycolysis but not that of glycogen synthesis was partly due to a phosphorylated metabolite of Itu. The present study indicates that despite their similar glycogenic effects, Itu and Pro do not share a common mechanism of action. Further, the inhibition of glycolysis and F-2,6-P2 formation by Itu cannot be explained if it acts solely as a general inhibitor of protein kinases.

Rats fasted for 36 h were refed for 1, 2, 4 or 6 h with a diet containing 12 g/100 g casein, 2 g/100 g NaCl and 86 g/100 g glucose, fructose, maltose, sucrose, starch or malt extract. Blood glucose reached constant levels after 1 to 2 h of refeeding. The increase in plasma insulin paralleled food intake rather than the increase in blood glucose. Plasma triglycerides decreased upon refeeding starch, maltose and malt extract and increased with sucrose and fructose. Recovery of absorbed carbohydrates was highest in rats refed malt extract. Glycogen deposition in muscle was highest in rats fed malt extract and lowest in those fed fructose; sucrose yielded intermediate values. Glucose, maltose and starch resulted in muscle glycogen depositions slightly lower than those obtained with malt extract. In liver, sucrose and fructose were better precursors for glycogen than glucose and starch. With carbohydrates containing only glucose units, much more glycogen was found to be deposited in total muscle than in liver. This asymmetry was less notable or even was reversed with sucrose and fructose. Glycogen deposition in muscle and in liver is influenced by the carbohydrate used for refeeding, and muscle, rather than liver, is the main glycogen storing tissue.

As shown previously, glycogen deposition in liver and muscle is significantly greater in rats fed a diet containing barley malt extract than in those fed diets containing glucose or starch. We investigated whether particular components of malt extract (glucose oligomers, inorganic salts, protein) were responsible for this effect. Food-deprived rats were fed diets containing carbohydrates of different chain lengths [glucose, maltose, maltodextrins or malt carbohydrates (84-86 g/100 g)] in the presence and absence of inorganic salts (2 g/100 g) and maltodextrin diets (78 g/100 g) containing either no protein or 20 g casein/100 g. Dietary glucose oligomers caused higher blood glucose concentrations than consumption of glucose or maltose but had no significant influence on liver or muscle glycogen. Salt addition resulted in higher muscle glycogen concentrations but had no effect on blood glucose or liver glycogen. Hepatic glycogen concentrations were significantly greater in rats fed casein compared with those fed no protein. We propose that consumption of malt extract has the following advantages over consumption of diets containing glucose or maltose: 1) better glucose absorption related to the presence of glucose oligomers, 2) greater hepatic glycogen concentrations associated with the protein in malt extract, and 3) greater glycogen concentrations in muscle due to the presence of inorganic salts.