A systematic review of in vitro studies evaluating the inhibitory effects of polyphenol-rich fruit extracts on carbohydrate digestive enzymes activity: a focus on culinary fruits consumed in Europe.

Evidence shows that polyphenols can attenuate postprandial blood glucose responses to meals containing digestible carbohydrate. Polyphenol-rich plant extracts are emerging as potential ingredients in functional foods and/or beverages despite limited understanding of their physiological effects. Many studies have investigated the mechanisms of polyphenol-rich fruit extracts on inhibition of digestive enzymes. However, the evidence available has yet to be critically evaluated systematically. This report reviews the in vitro literature to quantify the effect of fruit polyphenol extracts on the activities of digestive carbohydrases. A systematic literature search was conducted using six science databases. Included studies, totaling 34 in number, were in vitro digestion models which quantified gut digestive enzyme(s) activity on starch digestion in the presence of fruit polyphenol extracts. Most studies assessed the effects of fruit extracts on either α-amylase (n = 30) or α-glucosidase (n = 30) activity. Studies were consistent overall in showing stronger inhibition of α-amylase compared to α-glucosidase by proanthocyanidin- and/or ellagitannin-rich fruit extracts. Recommendations are proposed for future reporting of this type of research to enable meaningful synthesis of the literature as a whole. Such knowledge could allow effective choices to be made for development of novel functional foods and beverages.

The small intestinal fructose transporters: site of dietary perception and evidence for diurnal and fructose sensitive control elements.

To obtain an insight into the mechanisms responsible for GLUT5 diurnality and fructose responsiveness, rats were gavaged at 9:00 AM or 6:00 PM with 1 g of fructose in the presence or absence of cycloheximide. After 4 h of fructose exposure, GLUT5 mRNA and protein levels increased 2-3.5-fold above the natural diurnal levels of expression. In situ hybridization and immunochemical analysis of GLUT5 mRNA and protein demonstrated that both diurnality and fructose responsiveness was confined to mature enterocytes. The protein synthesis inhibitor, cycloheximide, blunted the diurnal and fructose driven increase in GLUT5 mRNA expression in the morning, but had minimal effect on the pattern of expression in the evening. This differential sensitivity of intestinal GLUT5 mRNA to de novo protein synthesis may reflect the increasing presence of diurnal and fructose sensitive control factors during the day. Following vehicle gavage, Cycloheximide was more effective in reducing GLUT5 protein expression levels in the morning when compared to the evening. These data suggest that the turnover of GLUT5 protein may be diurnally influenced.

Hexose transporter expression in rat small intestine: effect of diet on diurnal variations.

In rodents, a number of intestinal digestive and absorptive processes demonstrate a diurnal pattern of activity. To investigate if the jejunal hexose transporters are regulated in such a diurnal fashion, the levels for the glucose and fructose transporter mRNA and proteins were determined at 6-h intervals over a 24-h control fed period. SGLT-1, GLUT-2, and GLUT-5 mRNA levels increased between two- and eightfold before the onset of peak feeding. GLUT-5 protein levels also varied in a diurnal fashion but were out of phase with the observed changes in GLUT-5 mRNA levels. In contrast, GLUT-2 protein levels remained relatively constant during the control fed 24-h period. The effect of dietary manipulations on the observed diurnal variation was also investigated. After only 3 h of feeding a 60% fructose-enriched diet, the levels of GLUT-5 mRNA and protein were significantly elevated. GLUT-5 mRNA and protein levels remained elevated relative to the level of control diet-fed animals over the ensuing 24 h and during the 7th day of fructose feeding. Exposure to elevated levels of fructose had no significant effect on the diurnal pattern of GLUT-2 and SGLT-1 mRNA. In contrast, GLUT-2 protein was rapidly downregulated during the length of the fructose feeding study. In conclusion, the data demonstrate a normal daily variation in the level of hexose transporter expression that can be rapidly modulated by diet.

The regulation of GLUT5 and GLUT2 activity in the adaptation of intestinal brush-border fructose transport in diabetes.

The adaptation of d-fructose transport in rat jejunum to experimental diabetes has been studied. In vivo and in vitro perfusions of intact jejunum with d-fructose revealed the appearance of a phloretin-sensitive transporter in the brush-border membrane of streptozotocin-diabetic rats which was not detectable in normal rats. The nature of the transporters involved was investigated by Western blotting and by d-fructose transport studies using highly purified brush-border and basolateral membrane vesicles. GLUT5, the major transporter in the brush-border membrane of normal rats, was not inhibited by d-glucose or phloretin. In contrast, GLUT2, the major transporter in the basolateral membrane of normal rats, was strongly inhibited by both D-glucose and phloretin. In brush-border membrane vesicles from diabetic rats, GLUT5 levels were significantly enhanced; moreover the presence of GLUT2 was readily detectable and increased markedly as diabetes progressed. The differences in stereospecificity between GLUT2 and GLUT5 were used to show that both transporters contributed to the overall enhancement of d-fructose transport measured in brush-border membrane vesicles and in vitro isolated loops from diabetic rats. However, overall d-fructose uptake in vivo was diminished. The underlying mechanisms and functional consequences are discussed.

Rapid regulation of rat jejunal glucose transport by insulin in a luminally and vascularly perfused preparation.

1. The regulation of glucose transport by physiological concentrations of insulin was investigated using a preparation of rat jejunum perfused in situ with 5 mM glucose on both sides. 2. Luminal uptake was 87% inhibited (P < 0.001) by 0.2 mM phlorizin, indicating that it occurred by means of the Na(+)-D-glucose cotransporter. Vascular uptake was completely abolished by 0.2 mM phloretin, indicating that it was facilitated in nature. 3. When infused into the vascular circuit, insulin (10(-11) to 10(-7) M) stimulated vascular, and inhibited luminal, glucose uptake to a similar extent. Maximal stimulation of vascular uptake was increased by 40% compared with control infusions (P < 0.01) and occurred at 10(-10) M insulin. These effects were independent of changes in metabolism and vascular glucose concentration. 4. The time taken for half-maximal stimulation of vascular uptake was 6.3 +/- 0.7 min and preceded that for inhibition of luminal uptake by 6.5 +/- 1.3 min (P < 0.02). 5. The rapid inhibition of luminal glucose uptake by the acute administration of insulin was also detected by perfusion of jejunal loops in vivo. 6. It is concluded that the transport steps involved in intestinal glucose uptake are subject to rapid regulation by physiological concentrations of insulin and that the initial site of action is on the vascular side.