Mucosal Α-glucosidases Research Articles

Slowly hydrolyzable property of microbial dextrans at the small intestinal α-glucosidase levels leads to the modulated glycemic responses in the mouse model

Dextran-type α-glucans have been known as non-digestible ingredients that can be considered prebiotics to promote colon health. However, recent studies have revealed that various α-linked glucosyl units are hydrolyzed to glucose by small intestinal α-glucosidases. This study analyzed the structural characteristics of exopolysaccharides (EPSs) from Weissella species, and the hydrolysis properties at both in vitro/in vivo levels were investigated. Compared with a previous in vitro digestion model using fungal α-hydrolytic enzymes, dextrans, which mainly consist of α-1,6 linkages with small amounts of α-1,3 linked glucose units, were slowly hydrolyzed to glucose by mammalian mucosal α-glucosidases, resulting in attenuation of the initial glycemic response following administration of EPS samples to mice via oral gavage. The results of this study demonstrate the concept of dextran-type α-glucans as glycemic carbohydrates rather than dietary fibers or prebiotics. Slowly digestible dextrans can be applied as a functional ingredient to regulate postprandial glucose delivery throughout the gastrointestinal tract.

Changes in the structure and enzyme binding of starches during in vitro enzymatic hydrolysis using mammalian mucosal enzyme mixtures

Starches are hydrolyzed into monosaccharides by mucosal α-glucosidases in the human small intestine. However, there are few studies assessing the direct digestion of starch by these enzymes. The objective of this study was to investigate the changes in the structure and enzyme binding of starches during in vitro hydrolysis by mammalian mucosal enzymes. Waxy maize (WMS), normal maize (NMS), high-amylose maize (HAMS), waxy potato (WPS), and normal potato (NPS) starches were examined. The order of the digestion rate was different compared with other studies using a mixture of pancreatic α-amylase and amyloglucosidase. NPS was digested more than other starches. WPS was more digestible than WMS. Hydrolyzed starch from NPS, NMS, WPS, WMS, and HAMS after 24 h was 66.4, 64.2, 61.7, 58.7, and 46.2 %, respectively. Notably, a significant change in the morphology, reduced crystallinity, and a decrease in the melting enthalpy of the three starches (NPS, NMS, and WPS) after 24 h of hydrolysis were confirmed by microscopy, X-ray diffraction, and differential scanning calorimetry, respectively. The bound enzyme fraction of NPS, NMS, and WPS increased as hydrolysis progressed. In contrast, HAMS was most resistant to hydrolysis by mucosal α-glucosidases in terms of digestibility, changes in morphology, crystallinity, and thermal properties.

Generating slow digestibility in cooked potatoes by modulating starch accessibility to α-amylase and mucosal α-glucosidase to different levels

Health issues associated with overconsuming rapidly digestible glycemic carbohydrates continue to be prevalent globally. Transforming starch digestion from a hyperglycemic response to a sustained dietary glucose profile is an ideal digestion scenario. Digesting starch to glucose requires α-amylase (AMY) and mucosal α-glucosidase (m-AG). AMY can quickly break down starch molecules, and m-AG functions as the gatekeeper of dietary glucose production. In this study of cooked potatoes, we hypothesize that slow glucogenesis from starch can be achieved by modulating the accessibility of AMY and m-AG to starch to different levels by modifying cell wall permeability by promoting cross-linking of calcium with endogenous pectins. Raw potato cubes were blanched with 0–500 mg/L calcium solution, followed by steaming. Fully cooked potatoes with the pre-treatment had up to 41% and 99% reduction of the permeability for dextran probes of 20 kDa and 70 kDa, respectively, and a non-detectable permeability of 150 kDa dextran. Permeability data indicated a decrease in the accessibility of AMY and a complete restriction of m-AG to access starch in cells supported by data on starch susceptibility to both AMY and m-AG separately. In vitro stimulated gastrointestinal digestion data demonstrated a blunt glucose profile with a reduction of RDS from 80% to 46% and an increase of SDS from 12% to 37%. By modulating starch accessibility to AMY and m-AG to different extents, cooked potatoes were fully digested with a slow glucose-released profile. The modification was a pre-treatment, and modified potatoes can be processed into potato foods, such as french fries, mashed potatoes, and others.

Structure, retrogradation and digestibility of waxy corn starch modified by a GtfC enzyme from Geobacillus sp. 12AMOR1

To lower the retrogradation and digestibility of waxy corn starch for different food applications, a novel thermostable GtfC type 4,6-α-glucanotransferase without N- and C- terminals (GsGtfC) from Geobacillus sp. 12AMOR1 was used. Waxy corn starch of 50 g/L was incubated with GsGtfC of 40–100 U/g substrate at 65 °C and pH 5.5 for 1 h. Its molecular weight, iodine affinity, XRD crystallinity, and FTIR ratio of heights of bands at 1047 and 1022 cm−1 decreased, but ratio of DP<6 to DP≥25 branches and degree of branching increased. GsGtfC cleaved α-1,4-glycosidic bonds and induced α-1,6-branching points to produce reuteran-likes polymers, which is different from Exiguobacterium sibiricum GtfC enzyme cleaving α-1,4-glycosidic bonds and synthesizing consecutive α-1,6-glycosidic bonds to produce isomalto/malto-oligosaccharides. GsGtfC modified waxy corn starch had significantly lower DSC retrogradation enthalpies during the storage at 4 °C for 3–14 days and significantly lower released glucose during the incubation with mammalian mucosal α-glucosidase at 37 °C for 10–360 min. GsGtfC at 100 U/g substrate increased slowly digestible portion from 11.07% to 24.11%.

Enzymatic modification of potato starch by amylosucrase according to reaction temperature: Effect of branch-chain length on structural, physicochemical, and digestive properties

Branch-chain elongated starches can be synthesized by amylosucrase (AS). In this study, potato starches with different branch-chain length were produced using the temperature-dependent elongation property of AS from Deinococcus geothermalis (DGAS). Decreasing the reaction temperature led to a significant rise in the length of the branch-chains, in addition to amylose content. As branch-chain length increased, B-type crystal structure increased significantly alongside it, and the thermal transitions were enhanced, suggesting that the crystalline structure was further stabilized. In addition, a decrease in solubility and swelling power was observed, whereas the gelatinization temperatures and peak viscosities increased accordingly. With respect to digestive properties, a remarkable rise in slowly digestible starch (0–19.8%) and resistant starch (38.2%–62.2%) contents was observed, along with an enhanced resistance to mammalian mucosal α-glucosidase. In conclusion, enzymatic modification by DGAS might be an innovative method to regulate the physicochemical and digestive properties of starches.

Potato starch modified by Streptococcus thermophilus GtfB enzyme has low viscoelastic and slowly digestible properties

Potato starch with high viscosity and digestibility cannot be added into some foods. To address this issue, a novel starch-acting enzyme 4,6-α-glucosyltransferase from Streptococcus thermophilus (StGtfB) was used. StGtfB decreased the iodine affinity and the molecular weight, but increased the degree of branching of starch at a mode quite different from glycogen 1,4-α-glucan branching enzyme (GBE). StGtfB at 5 U/g substrate mainly introduced DP 1–7 into amylose (AMY) or DP 1–12 branches into amylopectin (AMP), and increased the ratio of short- to long-branches from 0.32 to 2.22 or from 0.41 to 2.50. The DP 3 branch chain was the most abundant in both StGtfB-modified AMY and StGtfB-modified AMP. The DP < 6 branch chain contents in StGtfB-modified AMY were 42.68%, much higher than those of GBE-modified AMY. StGtfB significantly decreased viscoelasticity but still kept pseudoplasticity of starch. The modifications also slowed down the glucose generation rate of products at the mammalian mucosal α-glucosidase level. The slowly digestible fraction in potato starch increased from 34.29% to 53.22% using StGtfB of 5 U/g starch. This low viscoelastic and slowly digestible potato starch had great potential with respect to low and stable postprandial blood glucose.

Conditioning with slowly digestible starch diets in mice reduces jejunal α-glucosidase activity and glucogenesis from a digestible starch feeding.

Maltase-glucoamylase (Mgam) and sucrase-isomaltase (Si) are mucosal α-glucosidases required for the digestion of starch to glucose. We hypothesized that a dietary approach to reduce Mgam and Si activities can reduce glucose generation and absorption, and improve glucose control. Rice starch was entrapped in alginate microspheres to moderate in vitro digestion properties. Three groups of 8-wk old mice (n = 8) were conditioned for 7 d with low 13C-starch-based materials differing in digestion rates (fast, slow, and slower), and then given a digestible 13C-labeled cornstarch test feeding to determine its digestion to glucose. Conditioning of the small intestine with the slowly digestible starches for 7 d reduced jejunal α-glucosidase and sucrase activities, as well as glucose absorption for the slowly digestible starch slower group (P < 0.01). A correlative relationship was found between glucose absorption from a cornstarch test feeding given at d 7 and jejunal α-glucosidase and sucrase activities (R2 = 0.64; 0.67). However, total prandial glucose levels during the 2-h feeding period did not differ. Decreased glucogenesis from a digestible starch feeding was found in mice conditioned on slowly digestible starch diets, suggesting that a dietary approach incorporating slowly digestible starches may change α-glucosidase activities to moderate glucose absorption rate.

Enzymatically elongated rice starches by amylosucrase from Deinococcus geothermalis lead to slow down the glucose generation rate at the mammalian α-glucosidase level

Amylosucrase (AS) catalyzes the transfer of a glucosyl unit from sucrose onto α-1,4-linked glucan polymers in starch. In this study, AS from Deinococcus geothermalis (DgAS) was applied to produce modified rice starches with slowly digestible properties. DgAS-treated waxy and normal rice starches showed significantly (p < 0.05) elevated degrees of polymerization, suggesting that the external chains were elongated. Additionally, the crystalline structures of starches changed from A- to B-type, and the temperature transition properties of enzymatically modified rice starches increased. The amounts of slowly digestible starch (SDS) increased remarkably (20.1% and 18.8%; waxy and normal rice starches, respectively), and the DgAS-treated rice starches were slowly hydrolyzed to glucose at the mammalian mucosal α-glucosidase level. Thus, DgAS-treated rice starches can be used to produce SDS-based ingredients that attenuate the glucose spike after glycemic food ingestion.

Citric-acid treatment during rice processing increases the level of slowly digestible starch with a potential to regulate the post-prandial blood glucose level

A recent study showed that the digestion of glycemic carbohydrates in the distal part of the small intestine has the potential to regulate satiety and food intake levels. In this study, we investigated different processing methods (oil-frying and popping) of rice with citric-acid treatment for the efficient regulation of glucose production in small intestinal mucosal α-glucosidases. Glucose generation from citric-acid-treated rice products was drastically decreased due to the cross-linking of the starch molecules. Interestingly, oil-frying or popping under high-temperature and high-pressure conditions can be used to process rice or other cereals for gelatinizing starch molecules without water. Thus, various rice processing methods combined with citric-acid treatment can be used to develop rice or cereal-based food products, which can attenuate glucose spikes and extend glucose delivery.

The Contribution of Different Subunits of Intestinal Mucosal α-glucosidases to the Glucose Release from Starches (P08-090-19)

ObjectivesTo analyze the role of each subunit from Sucrase-Isomaltase (SI) and Maltase-Glucoamylase (MG) on the glucose production from corn starch (NC), Waxy starch (WX) and Hylon V (HLV) starch predigested with pancreatic amylase (Amy). MethodsThe starches were selected based on their ratios of α-1,4 and α-1,6 linkages. Starches were predigested with Amy for 0, 10, 20, 30, 60 and 120 min. After predigestion starches were hydrolyzed with different combinations of recombinant C terminal (C) and N terminal (N) subunits of Sucrase-Isomaltase (SI) and Maltase-Glucoamylase (MG), each at the relative maltase activity of: 40% C-SI, 20% N-SI, 32% C-MG and 8% N-MG, resembling the observed in the human intestinal mucosa. Glucose release was quantified by a real-time glucose oxidase-peroxidase method at 37°C. ResultsC-MG subunit hydrolyzed the three starches without predigestion by Amy at rates of 2.9 ± 0.02, 2.5 ± 0.02 and 2.4 ± 0.05 ng/min of glucose for WX, HLV and NC, respectively. C-SI subunit produced only 0.9 ± 0.02 ng/min glucose from the starches not predigested by Amy. After 30 min of Amy predigestion, the rates of glucose release by C-MG were modified to 13.3 ± 0.09, 12.3 ± 0.08 and 11.6 ± 0.08 ng/min for HLV, NC and WX, respectively. The same predigestion modified glucose release by C-SI subunit to 3.9 ± 0.02, 4.7 ± 0.08 and 5.8 ± 0.03 for WX, NC and HLV, respectively. In starches predigested 60 or 120 min, C-MG subunit alone or together with N-MG showed lower activity than expected, suggesting the occurrence of substrate inhibition. Together the four MG and SI subunits showed clear differences on the rates of glucose production from the starches predigested with Amy for 120 min (22.8 ± 0.133 for WX, 26.4 ± 0.2 for NC and 26.7 ± 0.8 for HLV; all ng/min) which correlated with the glucose production by the N and C SI subunits together (15.5 ± 0.9 for WX, 19.4 ± 0.09 for NC and 23.85 ± 0.12 for HLV; all ng/min). ConclusionsWe found complex interactions among the starch structure, extent of amylase digestion and the rate of glucose release by each C and N subunits of SI and MG. Thus, the rate of intestinal starch digestion depends on the structure of the starches, the predigestion by amylase and, importantly, the relative abundance and catalytic properties of the individual subunits of MG and SI. Funding SourcesConsejo Nacional de Ciencias y Tecnología (CONACyT), Mexico.

Different inhibition properties of catechins on the individual subunits of mucosal α-glucosidases as measured by partially-purified rat intestinal extract.

Mucosal α-glucosidases from rat intestinal powder were employed, with a step to remove α-amylase, to measure the possibility of different inhibition of catechins, particularly those found in tea, on the four α-glucosidase enzymes. Inhibition of catechins was investigated for the slowing of digestion of glycemic carbohydrates, thus regulating glucose release and absorption. The α-glucosidases were fractionated using size-exclusion chromatography. The partially purified fractions showed higher α-glucosidase activity without any α-amylase activity. Catechins had selective inhibition properties on the α-glucosidases. In particular, (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) showed comparably high inhibitory effect on all four individual α-glucosidases, while (-)-epicatechin (EC), and (+)-catechin (C) indicated a more discriminating effect with relatively higher inhibitory effects on sucrase-isomaltase. The findings suggest that catechins differently inhibit the individual subunits of the α-glucosidases, and that they could modulate postprandial blood glucose levels through slowing digestion rate of starch and other glycemic carbohydrates, including sucrose.

Optimization of in vitro carbohydrate digestion by mammalian mucosal α-glucosidases and its applications to hydrolyze the various sources of starches

Glycemic carbohydrates, such as starch and sucrose, are fully hydrolyzed into monosaccharides by mucosal α-glucosidases in the small intestine. In this study, we optimized the reaction conditions of mammalian mucosal α-glucosidases to digest various types of glycemic carbohydrates to determine their hydrolytic activity. The results clearly showed that mammalian mucosal α-glucosidases had different hydrolytic properties compared to fungal amyloglucosidase, which is commonly used in vitro assay to determine carbohydrate quality, on various sizes and α-linked carbohydrates. Furthermore, non-gelatinized and gelatinized starches from different botanical sources were differently hydrolyzed to glucose by the prepared solution of mammalian α-glucosidases and porcine pancreatic α-amylase. Thus, it is clearly suggested that the digestion of glycemic carbohydrates by the optimized reaction condition with mammalian mucosal α-glucosidases and pancreatic α-amylase can be applied to determine the carbohydrate quality and digestion properties as it is more reliable to human digestive enzymes compared to fungal or microbial α-glucosidases.

Maltase Has Most Versatile α-Hydrolytic Activity Among the Mucosal α-Glucosidases of the Small Intestine.

Complete digestion of the glycemic carbohydrates to glucose takes place through the combined action of the 4 mucosal α-glucosidases (maltase-glucoamylase and sucrase-isomaltase) in the small intestine. Maltase digests α-1,2- and α-1,3-disaccharides better than the other α-glucosidases, and has, as well, the capability to effectively hydrolyze α-1,4 and α-1,6 linkages that form the major backbone of a starch molecule. This broad hydrolytic activity on α-linkages makes it an enzyme that has the most versatile α-hydrolytic activity among the 4mucosal α-glucosidases. The slowly digestible properties of the unusual linkages from this research suggest the development of new glycemic oligosaccharides which will be hydrolyzed slowly, compared to α-1,4 linkages, for modulating the postprandial glycemic response. In addition, using mammalian mucosal α-glucosidases is a better fit to characterize carbohydrate digestion properties, compared to fungal amyloglucosidase which is currently applied in in vitro assays.

Effects of raw potato starch on body weight with controlled glucose delivery

Starch digestion in the gastrointestinal tract has different properties depending on its botanical source. In this study, corn, wheat, rice, and potato starches were used to test the digestion properties of mammalian mucosal α-glucosidase in an in vitro assay, and their physiological effects were investigated in male C57BL/6 mice. The results clearly demonstrated that potato starch caused the lowest rates of glucose generation, suggesting that it can attenuate the postprandial glucose spike. Interestingly, a potato starch-based diet caused significantly (P < 0.05) lower weight gain and fat accumulation compared to diets based on other starches, through increased insulin sensitivity. This result suggests that potato starch-based products can be used to regulate postprandial blood glucose levels, aiding in the control of metabolic diseases.

Dietary starch breakdown product sensing mobilizes and apically activates α-glucosidases in small intestinal enterocytes.

Dietary starch is finally converted to glucose for absorption by the small intestine mucosal α-glucosidases (sucrase-isomaltase [SI] and maltase-glucoamylase), and control of this process has health implications. Here, the molecular mechanisms were analyzed associated with starch-triggered maturation and transport of SI. Biosynthetic pulse-chase in Caco-2 cells revealed that the high MW SI species (265 kDa) induced by maltose (an α-amylase starch digestion product) had a higher rate of early trafficking and maturation compared with a glucose-induced SI (245 kDa). The maltose-induced SI was found to have higher affinity to lipid rafts, which are associated with enhanced targeting to the apical membrane and higher activity. Accordingly, in situ maltose-hydrolyzing action was enhanced in the maltose-treated cells. Thus, starch digestion products at the luminal surface of small intestinal enterocytes are sensed and accelerate the intracellular processing of SI to enhance starch digestion capacity in the intestinal lumen.-Chegeni, M., Amiri, M., Nichols, B. L., Naim, H. Y., Hamaker, B. R. Dietary starch breakdown product sensing mobilizes and apically activates α-glucosidases in small intestinal enterocytes.

Amelioration of obesity in high-fat diet-fed mice by chestnut starch modified by amylosucrase from Deinococcus geothermalis

The ameliorative effect of enzymatically modified chestnut starch on high-fat diet (HFD)-induced obesity in a mouse model and the underlying mechanism were investigated. Chestnut starch was enzymatically modified by amylosucrase from Deinococcus geothermalis (DGAS). In vitro analyses including Englyst's assay and determination of the starch digestive pattern to investigate starch digestibility revealed that chestnut starch naturally contained higher slowly digestible starch and resistant starch than corn starch. Modification of chestnut native starch by DGAS increased the proportion of resistant starch, rendering it unavailable for catalysis by small-intestinal mucosal α-glucosidase. The amylose ratio and branch-chain of amylopectin in chestnut starch were increased by DGAS. In an in vivo study, HFD (45% kcal from fat)-induced obese C57BL/6 model mice were orally administered DGAS-modified chestnut starch at the dose of 1500 mg/kg b·w for 10 weeks. Supplementation of DGAS-modified chestnut starch to obese mice significantly reduced features of obesity as compared with HFD- or native chestnut starch-fed mice. Food intake and the gut hormones PYY and GLP-1 were not significantly changed. However, we found that feeding DGAS-modified chestnut starch led to a significant increase in empty cecum weight, indicating short-chain fatty acid production in the cecum. Additionally, DGAS-modified chestnut starch induced the short-chain fatty acid receptor GPR43-mediated suppression of insulin signaling. Changes in all these factors were resistant starch content-dependent. In conclusion, DGAS modification of chestnut starch increases non-digestible resistant starch and this ameliorates diet-induced obesity via GPR43-mediated suppression of insulin signaling, thereby presumably reducing fat accumulation in white adipose tissue.

Improved Starch Digestion of Sucrase-deficient Shrews Treated With Oral Glucoamylase Enzyme Supplements.

Although named because of its sucrose hydrolytic activity, this mucosal enzyme plays a leading role in starch digestion because of its maltase and glucoamylase activities. Sucrase-deficient mutant shrews, Suncus murinus, were used as a model to investigate starch digestion in patients with congenital sucrase-isomaltase deficiency.Starch digestion is much more complex than sucrose digestion. Six enzyme activities, 2 α-amylases (Amy), and 4 mucosal α-glucosidases (maltases), including maltase-glucoamylase (Mgam) and sucrase-isomaltase (Si) subunit activities, are needed to digest starch to absorbable free glucose. Amy breaks down insoluble starch to soluble dextrins; mucosal Mgam and Si can either directly digest starch to glucose or convert the post-α-amylolytic dextrins to glucose. Starch digestion is reduced because of sucrase deficiency and oral glucoamylase enzyme supplement can correct the starch maldigestion. The aim of the present study was to measure glucogenesis in suc/suc shrews after feeding of starch and improvement of glucogenesis by oral glucoamylase supplements. Sucrase mutant (suc/suc) and heterozygous (+/suc) shrews were fed with C-enriched starch diets. Glucogenesis derived from starch was measured as blood C-glucose enrichment and oral recombinant C-terminal Mgam glucoamylase (M20) was supplemented to improve starch digestion. After feedings, suc/suc and +/suc shrews had different starch digestions as shown by blood glucose enrichment and the suc/suc had lower total glucose concentrations. Oral supplements of glucoamylase increased suc/suc total blood glucose and quantitative starch digestion to glucose. Sucrase deficiency, in this model of congenital sucrase-isomaltase deficiency, reduces blood glucose response to starch feeding. Supplementing the diet with oral recombinant glucoamylase significantly improved starch digestion in the sucrase-deficient shrew.

Number of branch points in α-limit dextrins impact glucose generation rates by mammalian mucosal α-glucosidases

α-Amylase first hydrolyzes starch structures to linear maltooligosaccharides and branched α-limit dextrins, then complete hydrolysis to glucose takes place through the mucosal α-glucosidases. In this study, we hydrolyzed waxy corn starch (WCS) by human pancreatic α-amylase to determine the digestion and structural properties of different size fractions of the branched α-limit dextrins. The α-amylolyzed WCS was separated by size exclusion chromatography, and the analyzed chromatograms showed four main hydrolyzate fractions. The first three eluted peaks (regions I–III) corresponded to branched α-limit dextrins, while region IV was the linear maltooligosaccharides. Based on the chromatographic and NMR analyses of the individual peaks, Region I, II, and III had multiple (>2), two, and one α-1,6 linkages, respectively, and region I was the most slowly hydrolyzed to glucose by mucosal α-glucosidases (hydrolysis rate: Region I<II<III<IV). This study shows the possibility of producing slowly digestible oligosaccharides that may decrease postprandial glycemic response and control glucose delivery to the body, to address metabolic syndrome-associated diseases.

Contribution of the Individual Small Intestinal α-Glucosidases to Digestion of Unusual α-Linked Glycemic Disaccharides.

The mammalian mucosal α-glucosidase complexes, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI), have two catalytic subunits (N- and C-termini). Concurrent with the desire to modulate glycemic response, there has been a focus on di-/oligosaccharides with unusual α-linkages that are digested to glucose slowly by these enzymes. Here, we look at disaccharides with various possible α-linkages and their hydrolysis. Hydrolytic properties of the maltose and sucrose isomers were determined using rat intestinal and individual recombinant α-glucosidases. The individual α-glucosidases had moderate to low hydrolytic activities on all α-linked disaccharides, except trehalose. Maltase (N-terminal MGAM) showed a higher ability to digest α-1,2 and α-1,3 disaccharides, as well as α-1,4, making it the most versatile in α-hydrolytic activity. These findings apply to the development of new glycemic oligosaccharides based on unusual α-linkages for extended glycemic response. It also emphasizes that mammalian mucosal α-glucosidases must be used in in vitro assessment of digestion of such carbohydrates.

Moving to a Broader Concept of Quality of Glycemic Carbohydrates

Dietary carbohydrates are important in providing energy to humans, but carbohydrates are increasingly thought of as “bad” foods associated with obesity, diabetics and associated diseases. The objective of this report is in regard to how moderating glucose delivery profiles might be done to affect physiologic endpoints that may address these public health problems. Several projects were conducted related to this new concept. Small intestinal mucosal α-glucosidases, as the glucose generation point in digestion, were applied to hydrolyze starches and α-amylase hydrolysates in vitro to elucidate slower digesting components of starch. Alginate-based microsphere embedded with starch were developed to deposit glucose at different rates in the small intestine and glucosidase activity, feeding behavior, hypothalamic neuropeptides, and gastric emptying were examined in rat and mouse models. We also conducted studies to examine how distally release glucose affects gastric empty rate in humans. Overall, our results show that relatively small amount of glucose from glycemic carbohydrates in the diet delivered distally creates certain same and second meal physiological effects including modulation of gastric emptying rate of nutrients for digestion and absorption into the body, and reduced food intake accompanied by a lowering of the orexigenic neuropeptides of the hypothalamus. Dietary glucose, in this context, becomes a bioactive molecule as it triggers physiological responses, in addition to its major energy providing role. Our goal in future research is to develop food technologies, as well as to identify practical approaches, using whole grain or whole foods, or a mixture of food ingredient and whole food, for such carbohydrate quality health-related effects.