Effects of D-psicose on Glycemic Response 205 tion of sucrase activity by L-arabinose in rabbits [23] and rats [14], however, they did not examine the intestinal α- amylase activity. We also showed that D-allose selectively inhibited the activities of intestinal enzymes in vitro, but no in vivo examination was performed in this experiment. In our previous study, we demonstrated that a diet containing 5% D-psicose increased liver glycogen content in rats fed a high-fat or a low-fat diet for 16 weeks [18]. We also observed that D-psicose significantly suppressed the incre- ment of plasma glucose concentration induced by oral carbohydrate (sucrose, maltose or starch) tolerance tests [19]. The present study supports our previous findings. Other α-glucosidase inhibitors [9–13, 24] such as acarbose are recognized as potent inhibitors of the activities of intestinal glucoamylase, maltase, and sucrase, and it has also been shown that acarbose has an inhibitory effect on pancreatic amylase activity [13]. In many advanced countries, starch accounts for approximately 60% of ingested carbo- hydrates, with sucrose accounting for 30%, and lactose accounting for 10% [12]. Since the digestion of both starch and sucrose are delayed by acarbose and D-psicose, these α-glucosidase inhibitors have valuable therapeutic effect in reducing postprandial hyperglycemia in diabetic patients. The majority of dietary carbohydrates are from starch, but sucrose is used in many foods as a sweetener or as another ingredient, and its daily intake in many advanced countries is large. It has been shown that Tris competitively inhibits intestinal sucrose ingestion in rats and human subjects [25], however, Tris is of no practical use, because of its unpleasant taste and the necessity of large doses. Thus, there are few known inhibitors of practical use such as L-arabinose that selectively inhibit intestinal sucrase and delay the ingestion of sucrose. D-Psicose is a rare natural sugar with a sweet taste. In this study, it suppressed the increase in plasma glucose after sucrose (−15%, calculated by area under the curve, Table 2), maltose (−14%), and starch (−23%) but showed no suppres- sion of the increase in plasma glucose after oral glucose loading in rats. These results suggest that D-psicose does not affect glucose absorption or gastric emptying. Among hexose structurally related to D-psicose, D-allose was equally potent in its inhibitory effect on the sucrose and mal- tose activities of intestinal mucosa in this study. Neither D- psicose nor D-allose inhibited amylases from rat pancreas, bacillus subtilis, or aspergillus oryzae. These results suggest that some specific interaction may exist among the enzymes, inhibitors, and the substrate to elicit the inhibitory action of D-psicose or D-allose. D-Psicose is prevalent in nature as a component of some plants and agricultural products [26–30]. It has a potent, sweet taste and low toxicity; the LD50 value was 16g/kg orally in rats in our previous tests [6]. D-Psicose caused no diarrhea at a dose of 10% of the dietary intake in the rat Vol. 45, No. 2, 2009 study [6]. Although a definite therapeutic value of other known α-glucosidase inhibitors in diabetic patients has been demonstrated, unpleasant side effects associated with incomplete absorption of dietary carbohydrates, ie, flatulence, abdominal discomfort, diarrhea [9, 10], and ileus-like symptoms [31], have been reported. These side effects may be due to the potent inhibition of pancreatic amylases and many intestinal enzymes, which in turn strongly inhibits the digestion of both sucrose and starch. As shown in this study, D-psicose only inhibited intestinal enzymes and the suppres- sion of amylase was weak, resulting in little adverse effect on the gastrointestinal tract. Recently, there have been skeptical studies concerning the long-term effects of α-glucosidase inhibitors, e.g. acarbose, in type 2 diabetes patients. Kaiser et al. [32] and Van De Laar et al. [33] reported that the long-term trials and meta- analysis studies have been criticized for the effects of α- glucosidase inhibitors. Furthermore, a recent systematic review of α-glucosidase inhibitors in patients with type 2 diabetes concluded that there was no evidence of any effect on morbidity or mortality [34]. It is not clear the hypo- glycemic effects and side effects of D-psicose in diabetic patients for long-term. However, these effects were clarified in our previous animal studies [6, 20, 35]. Therefore, we will examine the long-term effects of D-psicose in clinical studies in future. In conclusion, the present study demonstrated that D- psicose inhibits intestinal sucrase and maltase activities and suppresses the plasma glucose increase after sucrose and maltose ingestion. Thus, D-psicose may be useful in pre- venting postprandial hyperglycemia in diabetic patients when foods containing sucrose and maltose are ingested. This is the first report indicating inhibition of sucrase and maltase activities by D-psicose both in vitro and in vivo. References [1] Green, G.M. and Perlin, A.S.: O-Isopropylidene derivatives of D-allulose (D-psicose) and D-erythro-hexopyranose-2,3- diulose. Can. J. Biochem., 46, 765–770, 1968. [2] Granstrom, T.B., Takata, G., Tokuda, M., and Izumori, K.: Izumoring: a novel and complete strategy for bioproduction of rare sugars. J. Biosci. Bioeng., 97, 89–94, 2004. [3] Matsuo, T., Suzuki, H., Hashiguchi, M., and Izumori, K.: D-Psicose is a rare sugar that provides no energy to growing rats. J. Nutr. Sci. Vitaminol., 48, 77–80, 2002. [4] Matsuo, T., Baba, Y., Hashiguchi, M., Takeshita, K., Izumori, K., and Suzuki, H.: Dietary D-psicose, a C-3 epimer of D- fructose, suppresses the activity of hepatic lipogenic enzymes in rats. Asia Pacific J. Clin. Nutr., 10, 233–237, 2001. [5] Matsuo, T., Baba, Y., Hashiguchi, M., Takeshita, K., Izumori, K., and Suzuki, H.: Less body fat accumulation with D- psicose diet versus D-fructose diet. J. Clin. Biochem. Nutr., 30, 55–65, 2001.