Interaction of dietary carbohydrate and glucagon in regulation of rat hepatic messenger ribonucleic acid S14 expression: role of circadian factors and 3',5'-cyclic adenosine monophosphate.

The mRNA of the rat hepatic S14 gene accumulates rapidly after administration of T3 and carbohydrate, making it an excellent model for studies of the effects of dietary and hormonal stimuli at the hepatocellular level. We undertook studies to assess circadian changes in responsivity of this sequence to intragastric sucrose administration combined with insulin injection, and evaluated the capacity of glucagon to reverse these effects. As in the case of T3, the response of mRNA-S14 to carbohydrate in the morning was brisk whereas there was no significant increment when the stimulus was applied in the evening. In confirmation of previous studies, glucagon markedly lowered levels of mRNA-S14 in the evening but exerted no effect in the morning. These results support the concept that the rate of hepatic production of mRNA-S14 in unmanipulated rats is maximal in the evening, thus allowing no further induction by carbohydrate or T3 but permitting reduction by glucagon. Conversely, the rate of production is minimal in the morning, permitting induction by carbohydrate or T3 but allowing no further reduction by glucagon. A major difference between the effects of carbohydrate and those of T3 was the observed failure of carbohydrate to reverse the effect of glucagon in the evening. The effect of glucagon was stimulated by (Bu)2cAMP, and this was reversed by T3. However, T3 did not modify the glucagon-induced increase in hepatic cAMP levels. We therefore conclude that the capacity of T3 to abolish the glucagon effect is mediated at a step distal to the generation of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)