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Diurnal Variation and Increase of Disaccharidase Activity in Diabetic Rats

The small intestinal disaccharidase activity and its daily variation in the diabetic rat have not been well described. Therefore, the small intestinal disaccharidase (maltase, lactase and sucrase) activity and its daily profile were studied in streptozotocin-induced diabetic rats under physiological conditions. In diabetic rats, a similar pattern of diurnal variation of disaccharidase activity to control rats was observed, while the relationships between daily change of disaccharidase activity and that of food consumption suggested that there was a different mechanism of diurnal variation in diabetic rats. On the other hand, a significant increase of mean 24-h lactase and sucrase activities was noted in diabetic rats, while that of maltase was not significant. Using the in vitro incubation method, a significant correlation between glucose concentration and lactase or sucrase activity but not maltase activity was observed. How ever, insulin showed no effect on disaccharidase activity. Thus we clarified the presence of a diurnal variation of disaccharidase activity and an increase in its activity in diabetic rats. This change was suggested to be derived from high plasma glucose level.

It has been known that disaccharidase (DS) activity in the small intestine in normal rats shows daily rhythmic change related to the time of food ingestion (1,2).
In the present study, we examined the DS activity and its daily profile in the small intestine of streptozotocin (STZ)-induced diabetic rats. For the purpose of clarifying the mechanism of daily variation of DS activity, its relationship with the amount of food ingestion and plasma glucose level was examined. Furthermore, to study the mechanism of increased DS activity, direct effects of glucose or insulin on DS activity in the small intestinal mucosal cells of rats were also examined in vitro.

DISCUSSION
In diabetic rats there have been no consistent results concerning DS activities in the small intestine. Some authors have reported increased activities (3,4,8), and others have observed no alteration of the activities in terms of the sites of sampling or duration of diabetes (12,13). This may be due to differences of times of sampling, which would affect DS activity due to the presence of diurnal variation in normal rats (1,2). Furthermore, DS activity itself (2,5) or the amplitude of diurnal variation (2) are known to be different depending on the sites of the small intestine. Therefore, in this study, we measured the enzyme activity at a consistent site.
In the present study, we were able to prove the presence of diurnal variations of maltase, lactase and sucrase activities in diabetic rats. These observations have not been previously reported.
Concerning the relation between DS activity and time of food ingestion in normal rats, increasing tendency of DS activity before food ingestion (1,2,23), and the maximum activities related to the time of food ingestion (24,25)  together with a decrease in DS activity. Then, preceding an increase of food consumption, an increase in DS activity was observed.
On the other hand, in diabetic rats, the diurnal variation of maltase or sucrase activity and food consumption suggested a relationship between them. Lactase activity showed similar changes to the daily profile of food consumption, with a lag phase of 4h.
Thus, some correlation between the amount of food ingestion and DS activity in terms of diurnal variation is present in both groups, although the mechanisms might be different between diabetic and control groups. Furthermore, it is suggested that the mechanism of daily change of lactase activity may be different from that of maltase or sucrase activities in the diabetic rat.
In both groups, daily profiles of plasma glucose levels showed no significant daily variation, suggesting no direct effect on the formation of diurnal variation of DS activity.
In our study, synchronized daily changes of DS activity between diabetic and control groups was observed. This may suggest the presence of a common mechanism for the induction of daily variations in both groups, but the precise mechanism was not demonstrated in the present study.
Saito et al. reported the continuation of daily changes of DS activity after at least 2days of cessation of food ingestion, after which time the diurnal variation became gradually more obscure and was finally lost after S days of fasting in normal rats (26,27). This data suggests the role of some intrinsic factor for the induction of daily change. In their reports they also observed no recovery of diurnal variation until after more than 8 to 9days of refeeding (26).
Concerning the mechanism of higher DS activity in diabetic rats, the role of hyperglycemia as a casual agent has been postulated (11,28), while that of poly phagia has been thought to be less important (3,4,8,29). In diabetic rats Olsen, W. A. and Korsmo, H. reported increased DS activity in Thiry-Vella fistula whose each end of a jejunal segment is open to the abdominal wall with intact nerve and blood supply (6). Furthermore, DS activity in the small intestine of diabetic rats has been found not to be different under conditions during which nutrients containing glucose and amino acids were administered intravenously or conditions during which they were infused directly to the stomach for 4days (30). These findings suggest that DS activity in diabetic rats was not directly influenced by the contact of food or digestive fluids with the small intestinal mucous membrane. Takeguchi et al. observed increased DS activity under acute hyperglycemia induced by i.v. administration of glucose in normal rats (11,28), and which was normalized by the correction of hyperglycemia with insulin administration (28).
On the other hand, the direct influence of glucose and insulin on DS activity had not been previously examined. In the present study, it was documented that lactase and sucrase activities were increased in vitro in the presence of high glucose. Meanwhile, any concentration of insulin did not alter DS activity in vitro. These results suggest the role of glucose in the regulation of both lactase and sucrase activities. Furthermore, it may explain the background of high lactase and sucrase activities in diabetic rats.
Lower DS activity in malnourished rats was reported by Firmansyah et al. (31). Although similar metabolic conditions like malnutrition may be present at the cellular level in diabetes, increased lactase and sucrase activities were detected. As a consequence, these changes of DS activity were interpreted to be characteristic of the diabetic condition.
These observations in diabetic rats might suggest not only the presence of diurnal variation of DS activity but also an increase of enzyme activity in human diabetics.
Concerning small intestinal DS activity in human diabetic patients, this is still controversial (14)(15)(16)(17). The reason might be due to the difference of sampling time in which daily changes of DS activity were not taken into consideration.
A positive correlation between the DS activity and the digestion and absorp tion of disaccharide is known (10). Therefore, increased DS activity in the diabetic state might influence the metabolic states through the increase of digestion and absorption of disaccharide.
In conclusion, in the diabetic rat, a diurnal variation of maltase, lactase and sucrase activities was documented and a pattern of food consumption was shown to correlate with these changes. Increased lactase and sucrase activities were also demonstrated in the diabetic rat; furthermore, the role of hyperglycemia on the enhancement of these enzyme activities was suggested in part to be important. More precise studies are necessary to elucidate the DS activity itself, its diurnal variation and the regulatory mechanisms of them in the diabetic state.