Intestinal absorption of D-fructose isomers, D-allulose, D-sorbose and D-tagatose, via glucose transporter type 5 (GLUT5) but not sodium-dependent glucose cotransporter 1 (SGLT1) in rats.

D-allulose, D-sorbose and D-tagatose are D-fructose isomers that are called rare sugars. These rare sugars have been studied intensively in terms of biological production and food application as well as physiological effects. There are limited papers with regard to the transporters mediating the intestinal absorption of these rare sugars. We examined whether these rare sugars are absorbed via sodium-dependent glucose cotransporter 1 (SGLT1) as well as via GLUT type 5 (GLUT5) using rats. High-fructose diet fed rats, which express more intestinal GLUT5, exhibited significantly higher peripheral concentrations, Cmax and AUC0­180 min when D-allulose, D-sorbose and D-tagatose were orally administrated. KGA-2727, a selective SGLT1 inhibitor, did not affect the peripheral and portal vein concentrations and pharmacokinetic parameters of these rare sugars. The results suggest that D-allulose, D-sorbose and D-tagatose are likely transported via GLUT5 but not SGLT1 in rat small intestine.

Long-term D-Allose Administration Favorably Alters the Intestinal Environment in Aged Male Mice.

D-Allose, a C3 epimer of D-glucose, has potential to improve human health as a functional food. However, its effect on the intestinal environment remains unknown. Aged humans progressively express changes in the gut, some of which deleteriously affect gastrointestinal health. In this study, we profiled the intestinal microbiome in aged mice and analyzed organic acids produced by bacteria in cecum contents after long-term ingestion of D-allose. D-Allose did not significantly change organic acid concentration. However, long-term ingestion did significantly increase the relative abundance of Actinobacteria and reduce the relative abundance of Proteobacteria. These results suggest that oral D-allose improves the proportion of favorable intestinal flora in aged mice. D-Allose significantly decreased the relative abundance of Lachnospiraceae bacteria, but increased the relative abundance of Bacteroides acidifaciens and Akkermansia muciniphila. Thus, D-allose might serve as a nutraceutical capable of improving the balance of gut microbiome during aging.

Dietary D-Allulose Reduces Body Fat Accumulation in Rats with and without Medium-Chain Triacylglycerol Supplementation.

d-Allulose (d-psicose) is a rare sugar, that contains no calories and exhibits 70% relative sweetness when compared with sucrose. Recently, several studies have demonstrated the anti-obesity effect of d-allulose, mediated by suppressing lipogenesis and increasing energy expenditure. Medium-chain triacylglycerols (MCTs) are lipids formed by 3 medium-chain fatty acids (MCFAs) with 6-12 carbon atoms attached to glycerol. MCTs have been expensively studied to reduce body fat accumulation in rats and humans. The anti-obesity effect of MCTs was not confirmed depending on the nutritional conditions because MCT might promote lipogenesis. In the present study, we examined the effects of simultaneous intake of diets containing low (5%) or high (13%) MCTs, with or without 5% d-allulose, on body fat accumulation in rats (Experiment 1). Furthermore, we assessed the interaction between 5% MCT and 5% d-allulose in the diet (Experiment 2). In Experiment 1, intra-abdominal adipose tissue weight was significantly greater in the high MCT diet groups than in the commercial diet (control) group. d-Allulose significantly decreased weights of intra-abdominal adipose tissue, carcass fat, and total body fat, however, these weights increased as the amount of MCT added increased. In Experiment 2, d-allulose significantly decreased almost all body fat indicators, and these values were not influenced by the presence or absence of MCT addition. The anti-obesity effect of d-allulose was observed with or without dietary MCT, and no synergistic effect was detected between d-allulose and MCT. These results suggest that d-allulose is a beneficial food ingredient in diets aimed at reducing body fat accumulation. However, further research is required on the synergistic effects between d-allulose and MCTs.

Combined effects of exercise training and D-allulose intake on endurance capacity in mice.

This study investigated the combined effects of exercise training and D-allulose intake on endurance capacity in mice. Male C57BL/6J mice were fed either a control diet (Con) or a 3% D-allulose diet (Allu) and further divided into the sedentary (Sed) or exercise training (Ex) groups (Con-Sed, Con-Ex, Allu-Sed, Allu-Ex, respectively; n = 6-7/group). The mice in the Ex groups were trained on a motor-driven treadmill 5 days/week for 4 weeks (15-18 m/min, 60 min). After the exercise training period, all mice underwent an exhaustive running test to assess their endurance capacity. At 48 h after the running test, the mice in the Ex groups were subjected to run at 18 m/min for 60 min again. Then the gastrocnemius muscle and liver were sampled immediately after the exercise bout. The running time until exhaustion tended to be higher in the Allu-Ex than in the Con-Ex group (p = 0.08). The muscle glycogen content was significantly lower in the Con-Ex than in the Con-Sed group and was significantly higher in the Allu-Ex than in the Con-Ex group (p < 0.05). Moreover, exercise training increased the phosphorylation levels of adenosine monophosphate-activated protein kinase (AMPK) in the muscle and liver. The phosphorylation levels of acetyl coenzyme A carboxylase (ACC), a downstream of AMPK, in the muscle and liver were significantly higher in the Allu-Ex than in the Con-Sed group (p < 0.05), suggesting that the combination of exercise training and D-allulose might have activated the AMPK-ACC signaling pathway, which is associated with fatty acid oxidation in the muscle and liver. Taken together, our data suggested the combination of exercise training and D-allulose intake as an effective strategy to upregulate endurance capacity in mice. This may be associated with sparing glycogen content and enhancing activation of AMPK-ACC signaling in the skeletal muscle.

A Simple Flow Injection Analysis-Tandem Mass Spectrometry Method to Reduce False Positives of C5-Acylcarnitines Due to Pivaloylcarnitine Using Reference Ions.

Flow injection analysis−tandem mass spectrometry (FIA-TMS) has been applied in a first-tier test of newborn screening (NBS). Although isovalerylcarnitine (i-C5), which is a diagnostic indicator of isovaleric acidemia (IVA), is isobaric with pivaloylcarnitine (p-C5), 2-methylbutyrylcarnitine, and n-valerylcarnitine, these isomers cannot be distinguished by the FIA-TMS. There are many reports of false positives derived from p-C5 due to the use of pivalate-conjugated antibiotics. In this study, we developed a new FIA-TMS method to distinguish i-C5 and p-C5. We found that the intensity ratio of product ions for i-C5 and p-C5 was different in a certain range even under the same analytical conditions. The product ions with the most distinct differences in ionic intensity between the isomers and the collision energies that produce them were determined to be m/z 246.2 > 187.1 and −15 V, respectively. In addition to the quantification ion, a reference ion was defined, and the similarity of the i-C5 and p-C5 reference ion ratios (i-C5 score and p-C5 score, respectively) were used to estimate which isomer (i-C5 and p-C5) was responsible for elevated C5 acylcarnitine in dried blood spots (DBSs). As a result of analyses of 11 DBS samples derived from pivalate-conjugated antibiotics and four DBS samples from IVA patients using our method, it was found that our method was able to correctly determine the type of C5-acylcarnitine (i-C5 or p-C5) in the DBS samples. Implementation of this new FIA-TMS method into the current NBS protocol will allow for a reduction in false positives in IVA.

d-Allulose Improves Endurance and Recovery from Exhaustion in Male C57BL/6J Mice.

d-Allulose, a rare sugar, improves glucose metabolism and has been proposed as a candidate calorie restriction mimetic. This study aimed to investigate the effects of d-allulose on aerobic performance and recovery from exhaustion and compared them with the effects of exercise training. Male C57BL/6J mice were subjected to exercise and allowed to run freely on a wheel. Aerobic performance was evaluated using a treadmill. Glucose metabolism was analyzed by an intraperitoneal glucose tolerance test (ipGTT). Skeletal muscle intracellular signaling was analyzed by Western blotting. Four weeks of daily oral administration of 3% d-allulose increased running distance and shortened recovery time as assessed by an endurance test. d-Allulose administration also increased the maximal aerobic speed (MAS), which was observed following treatment for >3 or 7 days. The improved performance was associated with lower blood lactate levels and increased liver glycogen levels. Although d-allulose did not change the overall glucose levels as determined by ipGTT, it decreased plasma insulin levels, indicating enhanced insulin sensitivity. Finally, d-allulose enhanced the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase and the expression of peroxisome proliferator-activated receptor γ coactivator 1α. Our results indicate that d-allulose administration enhances endurance ability, reduces fatigue, and improves insulin sensitivity similarly to exercise training. d-Allulose administration may be a potential treatment option to alleviate obesity and enhance aerobic exercise performance.

d-allulose protects against diabetic nephropathy progression in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes.

d-allulose is a rare sugar that has been reported to possess anti-hyperglycemic effects. In the present study, we hypothesized that d-allulose is effective in attenuating the progression of diabetic nephropathy in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of type 2 diabetes mellitus. Drinking water with or without 3% d-allulose was administered to OLETF rats for 13 weeks. Long-Evans Tokushima Otsuka rats that received drinking water without d-allulose were used as non-diabetic control rats. d-allulose significantly attenuated the increase in blood glucose levels and progressive mesangial expansion in the glomerulus, which is regarded as a characteristic of diabetic nephropathy, in OLETF rats. d-allulose also attenuated the significant increases in renal IL-6 and tumor necrosis factor-α mRNA levels in OLETF rats, which is a proinflammatory parameter. Additionally, we showed that d-allulose suppresses mesangial matrix expansion, but its correlation with suppressing renal inflammation in OLETF rats should be investigated further. Collectively, our results support the hypothesis that d-allulose can prevent diabetic nephropathy in rats.

d-Allulose Ameliorates Skeletal Muscle Insulin Resistance in High-Fat Diet-Fed Rats.

BACKGROUND: d-Allulose is a rare sugar with antiobesity and antidiabetic activities. However, its direct effect on insulin sensitivity and the underlying mechanism involved are unknown. OBJECTIVE: This study aimed to investigate the effect of d-allulose on high-fat diet (HFD)-induced insulin resistance using the hyperinsulinemic-euglycemic (HE)-clamp method and intramuscular signaling analysis. METHODS: Wistar rats were randomly divided into three dietary groups: chow diet, HFD with 5% cellulose (HFC), and HFD with 5% d-allulose (HFA). After four weeks of feeding, the insulin tolerance test (ITT), intraperitoneal glucose tolerance test (IPGTT), and HE-clamp study were performed. The levels of plasma leptin, adiponectin, and tumor necrosis factor (TNF)-α were measured using the enzyme-linked immunosorbent assay. We analyzed the levels of cell signaling pathway components in the skeletal muscle using Western blotting. RESULTS: d-allulose alleviated the increase in HFD-induced body weight and visceral fat and reduced the area under the curve as per ITT and IPGTT. d-Allulose increased the glucose infusion rate in the two-step HE-clamp test. Consistently, the insulin-induced phosphorylation of serine 307 in the insulin receptor substrate-1 and Akt and expression of glucose transporter 4 (Glut-4) in the muscle were higher in the HFA group than HFC group. Furthermore, d-allulose decreased plasma TNF-α concentration and insulin-induced phosphorylation of stress-activated protein kinase/Jun N-terminal kinase in the muscle and inhibited adiponectin secretion in HFD-fed rats. CONCLUSIONS: d-allulose improved HFD-induced insulin resistance in Wistar rats. The reduction of the proinflammatory cytokine production, amelioration of adiponectin secretion, and increase in insulin signaling and Glut-4 expression in the muscle contributed to this effect.

Investigation of d-allulose effects on high-sucrose diet-induced insulin resistance via hyperinsulinemic-euglycemic clamps in rats.

d-Allulose, a C-3 epimer of d-fructose, is a rare sugar that has no calories. Although d-allulose has been reported to have several health benefits, such as anti-obesity and anti-diabetic effects, there have been no reports evaluating the effects of d-allulose on insulin resistance using a hyperinsulinemic-euglycemic clamp (HE-clamp). Therefore, we investigated the effects of d-allulose on a high-sucrose diet (HSD)-induced insulin resistance model. Wistar rats were randomly divided into three dietary groups: HSD containing 5% cellulose (HSC), 5% d-allulose (HSA), and a commercial diet. The insulin tolerance test (ITT) and HE-clamp were performed after administration of the diets for 4 and 7 weeks. After 7 weeks, the muscle and adipose tissues of rats were obtained to analyze Akt signaling via western blotting, and plasma adipocytokine levels were measured. ITT revealed that d-allulose ameliorated systemic insulin resistance. Furthermore, the results of the 2-step HE-clamp procedure indicated that d-allulose reversed systemic and muscular insulin resistance. d-Allulose reversed the insulin-induced suppression of Akt phosphorylation in the soleus muscle and epididymal fat tissues and reduced plasma TNF-α levels. This study is the first to show that d-allulose improves systemic and muscle insulin sensitivity in conscious rats.

d-Allose is absorbed via sodium-dependent glucose cotransporter 1 (SGLT1) in the rat small intestine.

d-Allose is the C3 epimer of d-glucose and has been reported to have beneficial health effects. The transporter mediating intestinal transport of d-allose is unknown. We examined whether d-allose is absorbed via sodium-dependent glucose cotransporter 1 (SGLT1) as well as via glucose transporter type 5 (GLUT5) using rats. For examination of absorption via SGLT1, KGA-2727, an SGLT1-specific inhibitor, and d-allose were orally administered. KGA-2727 blocked the increase of plasma d-allose levels and suppressed them throughout the experiment (0-180 min), whereas without KGA-2727, the plasma d-allose levels peaked at around 60-90 min. For examination of absorption via GLUT5, rats were fed a high-fructose diet for 3weeks to increase the abundance and activity of GLUT5 in the small intestine. High-fructose diet-fed rats did not exhibit significant changes in the plasma d-allose levels compared to control rats fed a high-glucose diet. These results indicate that SGLT1 but not GLUT5 mediates the intestinal absorption of d-allose.

A simple and rapid method to simultaneously analyze ciclesonide and its impurities in a ciclesonide metered-dose inhaler using on-line supercritical fluid extraction/supercritical fluid chromatography/quadrupole time-of-flight mass spectrometry.

A simple and rapid on-line SFE/SFC/quadrupole TOF-MS method to simultaneously analyze active pharmaceutical ingredients and impurities from metered-dose inhalers (MDIs) was developed using ciclesonide MDI (CIC-MDI) as an example. CIC-MDI, as drug Alvesco®, has been approved for the treatment of bronchial asthma, and its major impurities are listed in the European Pharmacopoeia and in the supplementary package inserts of Alvesco® (called as "Pharmaceutical interview form" in Japan). In the developed method, CIC-MDI was manually sprayed only once on a glass disc prior to the SFE/SFC/quadrupole TOF-MS. In the SFE, CIC and its impurities and other impurities having various polarities and hydrophobicity, were extracted in 3.5 min and subsequently separated on a CHIRALPAK IE-3 column to be detected by quadrupole TOF-MS in 6.5 min. This method would be applicable to the analysis of other inhalable pharmaceutical products whose sample preparation requires complicated procedures, as well as to the analysis of general pharmaceutical products for profiling impurities.

Effect of D-allulose feeding on the hepatic metabolomics profile in male Wistar rats.

The rare sugar d-allulose is a C-3 epimer of d-fructose and is known to have several health benefits such as anti-obesity and anti-diabetic effects through the alteration of enzymatic and genetic expressions in each organ. Most of the ingested d-allulose is absorbed in the small intestine and then rapidly excreted in the urine. As d-allulose was reported to be present in the liver before it is excreted, d-allulose may modulate some hepatic metabolites including glucose and lipid metabolism. Therefore, we investigated the hepatic metabolomics profile in rats after feeding d-allulose to study the overall alteration of hepatic metabolism. Wistar rats were fed an AIN-93G diet with/without 3% d-allulose for 4 weeks. Their liver samples were then collected and subjected to metabolomics analysis using CE-TOFMS and LC-TOFMS. The results showed that d-allulose induced significant increases in 42 metabolites and significant decreases in 21 metabolites. In particular, we found at the substance levels that d-allulose regulated metabolites involved in the metabolic pathways of fatty acid ß-oxidation, cholesterol, and bile acid. In addition, this study newly showed the possibility that d-allulose alters glucuronic acid/xylulose pathways. In the future, we need more detailed research on the metabolomics profile of other organs related to these pathways for a comprehensive understanding of d-allulose functions.

An acidic morpholine derivative containing glyceride from thraustochytrid, Aurantiochytrium.

A novel acidic morpholine-derivative containing glyceride (M-glyceride) was isolated from the cells of two strains of the thraustochytrid, Aurantiochytrium. The glyceride accounted for approximately 0.1 -0.4% of the lyophilized cells. The glyceride consisted of peaks I (85%) and II (15%). The structures of the intact and acetylated glycerides were elucidated by liquid chromatography-quadrupole time-of-flight chromatograph mass spectrometer (LC-Q/TOF) and NMR spectroscopy. The hydrate type of M-glyceride was detected as a minor component by LC-MS/MS. By 2D-NMR experiments, peaks I of the intact M-glyceride were elucidated as 1,2-didocosapentaenoyl-glyceryl-2'-oxy-3'-oxomorpholino propionic acid, and peak II was estimated 1,2-palmitoyldocosapentaenoyl- and/or 1,2-docosapentaenoylpalmitoyl-glyceryl-2'-oxy-3'-oxomorpholino propionic acid. The double bond position of docosapentaenoic acid was of the ω - 6 type (C22 = 5.ω - 6). The M-glyceride content varied by the cell cycle. The content was 0.4% of lyophilized cells at the mid logarithmic phase, and decreased to 0.1% at the mid stationary phase. When cells were grown in 1.0 µM M-glyceride-containing growth media, cell growth was stimulated to 110% of the control. With 0.1 µM acetyl M-glyceride, stimulation of 113% of the control was observed. Finding morpholine derivatives in biological components is rare, and 2-hydroxy-3-oxomorpholino propionic acid (auranic acid) is a novel morpholine derivative.

Effects of D-allulose on glucose tolerance and insulin response to a standard oral sucrose load: results of a prospective, randomized, crossover study.

INTRODUCTION: Current dietary guidelines recommend limiting sugar intake for the prevention of diabetes mellitus (DM). Reduction in sugar intake may require sugar substitutes. Among these, D-allulose is a non-calorie rare monosaccharide with 70% sweetness of sucrose, which has shown anti-DM effects in Asian populations. However, there is limited data on the effects of D-allulose in other populations, including Westerners. RESEARCH DESIGN AND METHODS: This was a prospective, randomized, double-blind, placebo-controlled, crossover study conducted in 30 subjects without DM. Study participants were given a standard oral (50 g) sucrose load and randomized to placebo or escalating doses of D-allulose (2.5, 5.0, 7.5, 10.0 g). Subjects crossed-over to the alternate study treatment after 7-14 days of wash out. Plasma glucose and insulin levels were measured at five time points: before and at 30, 60, 90 and 120 min after ingestion. RESULTS: D-allulose was associated with a dose-dependent reduction of plasma glucose at 30 min compared with placebo. In particular, glucose was significantly lower with the 7.5 g (mean difference: 11; 95% CI 3 to 19; p=0.005) and 10 g (mean difference: 12; 95% CI 4 to 20; p=0.002) doses. Although glucose was not reduced at the other time points, there was a dose-dependent reduction in glucose excursion compared with placebo, which was significant with the 10 g dose (p=0.023). Accordingly, at 30 min D-allulose was associated with a trend towards lower insulin levels compared with placebo, which was significant with the 10 g dose (mean difference: 14; 95% CI 4 to 25; p=0.006). D-allulose did not reduce insulin at any other time point, but there was a significant dose-dependent reduction in insulin excursion compared with placebo (p=0.028), which was significant with the 10 g dose (p=0.002). CONCLUSIONS: This is the largest study assessing the effects of D-allulose in Westerners demonstrating an early dose-dependent reduction in plasma glucose and insulin levels as well as decreased postprandial glucose and insulin excursion in subjects without DM. These pilot observations set the basis for large-scale investigations to support the anti-DM effects of D-allulose. TRIAL REGISTRATION NUMBER: NCT02714413.

D-Allulose enhances uptake of HDL-cholesterol into rat's primary hepatocyte via SR-B1.

D-Allulose, a C-3 epimer of D-fructose, is a rare sugar and a non-caloric sweetener. D-Allulose is reported to have several health benefits, such as suppressing a rise in postprandial glucose levels and preventing fat accumulation in rodents and humans. Additionally, low HDL-cholesterol levels post-D-allulose feeding were observed in humans but it is unclear how D-allulose decreased HDL-cholesterol levels. It is necessary to research the mechanism of HDL-cholesterol reduction by D-allulose ingestion because low HDL-cholesterol levels are known to associate with increased atherosclerosis risk. We therefore investigated the mechanism by which D-allulose lowers HDL-cholesterol using rat's primary hepatocytes. Sprague Dawley rats were fed an AIN-93G based diet containing 3% D-allulose for 2 weeks. Thereafter, primary hepatocytes were isolated by perfusion of collagenase. We measured the ability of HDL-cholesterol uptake in hepatocytes and the protein levels of scavenger receptor class B type 1 (SR-B1) as a HDL-cholesterol receptor. D-Allulose enhanced hepatocyte uptake of HDL-cholesterol, with a concurrent increase in hepatic SR-B1 protein levels. The results suggest that D-allulose enhances HDL-cholesterol uptake into the liver by increasing SR-B1 expression. It is estimated that HDL-cholesterol levels decreased accordingly. Since SR-B1 overexpression would decrease HDL-cholesterol levels, reportedly preventing atherosclerosis development, D-allulose could be a useful sweetener for atherosclerosis prevention.

Naturally occurring rare sugars are free radical scavengers and can ameliorate endoplasmic reticulum stress.

Because of potential use of naturally occurring rare sugars as sweeteners, their effect on superoxide (SO), hydroxyl and peroxyl radicals and endoplasmic reticulum (ER) stress was examined in human coronary artery endothelial cells. SO generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride chemiluminescence. Phycoerythrin fluorescence based assay was used to monitor scavenging activity of sugars in the presence of hydroxyl or peroxyl radical generators [CuSO4 and azobis (2 amidinopropane) hydrochloride respectively]. Measurements were made in relative light units (RLU). ER stress was measured with an ER stress-sensitive secreted alkaline phosphatase (SAP) assay and by Western blot analysis of the expression and phosphorylation of key proteins in the unfolded protein response, namely CHOP47, eIF2α and JNK1. D-Glucose (27.5 mM) increased SO generation (5536 ± 283 vs. 2963 ± 205 RLU in controls; p < 0.0007) and decreased SAP secretion (73411 ± 3971 vs. 101749 ± 7652 RLU in controls; p < 0.005) indicating ER stress. Treatment of cells with 5.5 or 27.5 mM of D-allulose, D-allose, D-sorbose and D-tagatose reduced SO generation (all p < 0.05). This could not be attributed to inhibition of cellular uptake of dextrose by the rare sugars tested. In a cell free system, all four rare sugars had significantly more SO, hydroxyl and peroxyl radical scavenging activity compared to dextrose (all p < 0.01). Treatment of cells with rare sugars reduced ER stress. However, unlike other three rare sugars, D-sorbose did not inhibit tunicamycin-induced eIF2α phosphorylation. Naturally occurring rare sugars are free radical scavengers and can reduce ER stress.

d-Allulose is a substrate of glucose transporter type 5 (GLUT5) in the small intestine.

d-Allulose has been reported to have beneficial health effects. However, the transport system(s) mediating intestinal d-allulose transport has not yet been clearly identified. The aim of this study was to investigate whether intestinal d-allulose transport is mediated by glucose transporter type 5 (GLUT5). When d-allulose alone was gavaged, plasma d-allulose levels were dramatically higher in rats previously fed fructose. This suggests enhanced intestinal d-allulose absorption paralleled increases in GLUT5 expression observed only in fructose-fed rats. When d-allulose was gavaged with d-fructose, previously observed increases in plasma d-allulose levels were dampened and delayed, indicating d-fructose inhibited transepithelial d-allulose transport into plasma. Tracer D-[14C]-fructose uptake rate was reduced to 54.8% in 50 mM d-allulose and to 16.4% in 50 mM d-fructose, suggesting d-allulose competed with D-[14C]-fructose and the affinity of d-allulose for GLUT5 was lower than that of d-fructose. GLUT5 clearly mediates, likely at lower affinity relative to d-fructose, intestinal d-allulose transport.

Secretion of GLP-1 but not GIP is potently stimulated by luminal d-Allulose (d-Psicose) in rats.

Glucagon-like peptide 1 (GLP-1), an incretin gastrointestinal hormone, is secreted when stimulated by nutrients including metabolizable sugars such as glucose and fructose. d-Allulose (allulose), also known as d-psicose, is a C-3 isomer of d-fructose and a rare sugar with anti-diabetic or anti-obese effects in animal models. In the present study, we examined whether an oral administration of allulose could stimulate GLP-1 secretion in rats, and investigated the underlying mechanisms. Oral, but not intraperitoneal, administration of allulose (0.5-2.0 g/kg body weight) elevated plasma GLP-1 levels for more than 2 h in a dose-dependent manner. The effects of allulose on GLP-1 secretion were higher than that of dextrin, fructose, or glucose. In addition, oral allulose increased total and active GLP-1, but not glucose-dependent insulinotropic polypeptide (GIP), levels in the portal vein. In anesthetized rats equipped with a portal catheter, luminal (duodenum and ileum) administration of allulose increased portal GLP-1 levels, indicating the luminal effect of allulose. Allulose-induced GLP-1 secretion was abolished in the presence of xanthohumol (a glucose/fructose transport inhibitor), but not in the presence of inhibitors of the sodium-dependent glucose cotransporter 1 or the sweet taste receptor. These results demonstrate a potent and lasting effect of orally administered allulose on GLP-1 secretion in rats, without affecting GIP secretion. The potent and selective GLP-1-releasing effect of allulose holds promise for the prevention and treatment of glucose intolerance through promoting endogenous GLP-1 secretion.

d-Allulose enhances postprandial fat oxidation in healthy humans.

OBJECTIVE: d-Allulose, a C-3 epimer of d-fructose, has been reported to decrease body weight and adipose tissue weight in animal studies and is expected to be a potent antiobese sweetener. Our animal study suggested that one of the mechanisms of d-allulose's antiobesity function is an increase in energy expenditure. However, a few studies have thus far explored the underlying mechanism in humans. The aim of this study was to examine the effects of a single ingestion of d-allulose on postprandial energy metabolism in healthy participants. METHODS: Thirteen healthy men and women (mean age of 35.7 ± 2.1 y and body mass index 20.9 ± 0.7 kg/m2) were studied. The study was a randomized, single-blind crossover design with a 1-wk washout period. At 30 min after taking 5 g of d-allulose or 10 mg of aspartame without any sugar as a control, overnight-fasted participants ingested a standardized meal, and energy metabolism was evaluated by a breath-by-breath method. During the experiment, blood was collected and biochemical parameters such as plasma glucose were analyzed. RESULTS: In the d-allulose-treated group, the area under the curve of fat oxidation was significantly higher than in the control group (10.5 ± 0.4 versus 9.6 ± 0.3 kJ·4 h·kg-1 body weight [BW]; P < 0.05), whereas that of carbohydrate oxidation was significantly lower (8.1 ± 0.5 versus 9.2 ± 0.5 kJ·4 h·kg-1 BW; P < 0.05). Furthermore, plasma glucose levels were significantly lower, and free fatty acid levels were significantly higher in the d-allulose group than in the control group. No other parameters such as insulin, total cholesterol, or triacylglycerol were modified. CONCLUSION: d-Allulose enhances postprandial fat oxidation in healthy humans, indicating that it could be a novel sweetener to control and maintain healthy body weight, probably through enhanced energy metabolism.

Comparison of Anti-Obesity Effect between Two Types of Syrup Containing Rare Sugars in Wistar Rats.

D-Allulose-containing rare sugar sweeteners have been categorized into two types, rare sugar syrup (RSS), consisting of 4 rare monosaccharides, and modified glucose syrup (MGS), rich in D-allulose, which was previously referred to D-psicose. The anti-obesity effect of RSS and D-allulose has been already clarified, but that of rare monosaccharides other than D-allulose in RSS has not yet been well understood. Here, we investigated and compared the anti-obesity effect of RSS and MGS in rats. Male Wistar rats were divided into 4 dietary groups: a high-sucrose control diet group (S), a high-fructose corn syrup diet group (HFCS), an RSS diet group (RSS), and an MGS diet group (MGS). RSS significantly suppressed abdominal adipose tissue weight and total body fat accumulation in comparison to sucrose. On the other hand, MGS reduced body weight gain, but not abdominal fat accumulation, relative to sucrose. The weight of the liver and kidneys was significantly higher in the RSS and MGS groups than in the S and HFCS groups, but serum biochemical parameters and hepatic lipids contents were not significantly different among the groups. The present study shows that two types of D-allulose-containing rare sugar sweeteners can suppress body fat accumulation or weight gain in a different manner and that RSS could be used as more effective sweeteners in place of sucrose and HFCS to maintain healthy body weight.