Abstract
It is widely accepted that in mammals, liver and kidney play main roles in gluconeogenesis. We have already revealed that one of key gluconeogenic enzymes, phosphoenolpyruvate carboxykinase (PEPCK) activities in liver and kidney showed a diurnal variation, and the variation in liver inversely related to that in kidney, in other words the enzyme in liver showed the highest activity in the afternoon and the lowest one in the morning, and that in kidney showed the lowest activity in the afternoon and the highest one in the morning. These suggested that the inverse relationship of the diurnal variations of PEPCK activity in liver to those in kidney might indicate a cooperation of these two organs so as to maintain blood glucose level in a narrow range. The animals used in the above experiments were fed ad libitum. Under these conditions, glucagon increased this enzyme activity in liver and decreased in kidney, and either insulin or carbachol decreased this enzyme activity in liver and increased in kidney1).
In this experiment, we want to clarify the correlation between liver and kidney in the activity of PEPCK especially from the viewpoint of homeostasis.
Male Wistar strain rats, weighing 110-130g initially, were fed on 25% casein diet ad libitum or only in the daytime for more than one week, then sacrificed. The activity of PEPCK was assayed by the method of Seubert and Huth2).
The diurnal variation of the enzyme in the liver of the rats that were used to be fed only in the daytime for more than one week, was reversed to that of the ad libitum fed rats. And that in kidney of these former rats tended to be reversed to that of the ad libitum fed rats. These findings suggest that these diurnal variations may associated with their feeding behavior. Moreover, according to this feeding schedule, either epinephrine or glucagon increased this enzyme activity in liver and decreased that in kidney. We have reported the induction of this enzyme in liver of rat by l-thyroxine3). Thus, we injected l-thyroxine (50μg/100g body weight/day) for three days to thyroidectomized rats which were fed ad libitum. This treatment increased the enzyme activity in liver and decreased in kidney.
Thus far the rats, in these experiments maintained their rhythms in the body. But we want to state another case in which the animals' rhythms were disturbed.
Recently, we also revealed that in the early stage of cold-exposure rats which fed ad libitum, their diurnal variation of this enzyme activity in liver was blocked4). So we examined the effect of cold-exposure on the enzyme activities of the rats fed ad libitum. This time, these enzyme activities in both the organs increased correspondingly on cold-exposure. This suggests that these two organs may respond to the requirement for gluconeogenesis in a cold environment.
While administration of such a great deal of 3, 3', 5-triiodothyronine as 100μg per 100g body weight daily to intact rats for 6 days, resulted in an increase in the enzyme activities in both the organs unlike the case of the above thyroxine treatment. These findings lead to the following suggestion. Liver and kidney in rats may respond inversely to stresses not disturbing their rhythms in the body. Thus, the enzyme activity may show diurnal variations in these organs keeping their inversibility in order to maintain their blood glucose levels. On the other hand, to large or urgent stresses bloking their rhythms in the body, liver and kidney may respond correspondingly by other mechanisms.
Accordingly, we must take these facts into consideration, that there are diurnal variations and inverse relationship in PEPCK activity in liver to that in kidney, and those diurnal variations are blocked by large or urgent stresses.