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1.
A mechanistic study of the poorly understood pathway by which the inhibitor acarbose is enzymatically rearranged by human pancreatic alpha-amylase has been conducted by structurally examining the binding modes of the related inhibitors isoacarbose and acarviosine-glucose, and by novel kinetic measurements of all three inhibitors under conditions that demonstrate this rearrangement process. Unlike acarbose, isoacarbose has a unique terminal alpha-(1-6) linkage to glucose and is found to be resistant to enzymatic rearrangement. This terminal glucose unit is found to bind in the +3 subsite and for the first time reveals the interactions that occur in this part of the active site cleft with certainty. These results also suggest that the +3 binding subsite may be sufficiently flexible to bind the alpha-(1-6) branch points in polysaccharide substrates, and therefore may play a role in allowing efficient cleavage in the direct vicinity of such junctures. Also found to be resistant to enzymatic rearrangement was acarviosine-glucose, which has one fewer glucose unit than acarbose. Collectively, structural studies of all three inhibitors and the specific cleavage pattern of HPA make it possible to outline the simplest sequence of enzymatic reactions likely involved upon acarbose binding. Prominent features incorporated into the starting structure of acarbose to facilitate the synthesis of the final tightly bound pseudo-pentasaccharide product are the restricted availability of hydrolyzable bonds and the placement of the transition state-like acarviosine group. Additional "in situ" experiments designed to elongate and thereby optimize isoacarbose and acarviosine-glucose inhibition using the activated substrate alphaG3F demonstrate the feasibility of this approach and that the principles outlined for acarbose rearrangement can be used to predict the final products that were obtained. 相似文献
2.
Acarbose analogues, containing cellobiose and lactose structures, were prepared by reaction of the two disaccharides with acarbose and Bacillus stearothermophilus maltogenic amylase. The kinetics for the inhibition by the two analogues was studied for beta-glucosidase, beta-galactosidase, cyclomaltodextrin glucanosyltransferase (CGTase), and alpha-glucosidase. Both analogues were potent competitive inhibitors for beta-glucosidase, with K(I) values in the range of 0.04-2.44 microM, and the lactose analogues were good uncompetitive inhibitors for beta-galactosidase, with K(I) values in the range of 159-415 microM, while acarbose was not an inhibitor for either enzyme at 10 and 5 mM, respectively. Both analogues were also potent mixed inhibitors for CGTase, with K(I) values in the range of 0.1-9.3 microM. The lactose analogue was a 6.4-fold better competitive inhibitor for alpha-glucosidase than was acarbose. 相似文献
3.
Acarbose analogues, 4IV-maltohexaosyl acarbose (G6-Aca) and 4IV-maltododecaosyl acarbose (G12-Aca), were prepared by the reaction of cyclomaltodextrin glucanyltransferase with cyclomaltohexaose and acarbose. The inhibition kinetics of acarbose and the two acarbose analogues were studied for four different alpha-amylases: Aspergillus oryzae, Bacillus amyloliquefaciens, human salivary, and porcine pancreatic alpha-amylases. The three inhibitors showed mixed, noncompetitive inhibition, for all four alpha-amylases. The acarbose inhibition constants, Ki, for the four alpha-amylases were 270, 13, 1.27, and 0.80 microM, respectively; the Ki values for G6-Aca were 33, 37, 14, and 7 nM, respectively; and the G12-Aca Ki constants were 59, 81, 18, and 11 nM, respectively. The G6-Aca and G12-Aca analogues are the most potent alpha-amylase inhibitors observed, with Ki values one to three orders of magnitude more potent than acarbose, which itself was one to three orders of magnitude more potent than other known alpha-amylase inhibitors. 相似文献
4.
Inhibition of alpha-glucosidase and amylase by luteolin, a flavonoid 总被引:11,自引:0,他引:11
Twenty-one naturally occurring flavonoids were tested for inhibitory activities against alpha-glucosidase (EC 3.2.1.20) and alpha-amylase (EC 3.2.1.1). Luteolin, amentoflavone, luteolin 7-O-glucoside, and daidzein were the strongest inhibitors among the compounds tested. Luteolin inhibited alpha-glucosidase by 36% at the concentration of 0.5 mg/ml and was stronger than acarbose, the most widely prescribed drug, in inhibitory potency, suggesting that it has the possibility to effectively suppress postprandial hyperglycemia in patients with non-insulin dependent diabetes mellitus. Luteolin also inhibited alpha-amylase effectively although it was less potent than acarbose. The clinical value of luteolin needs to be further evaluated. 相似文献
5.
《Bioscience, biotechnology, and biochemistry》2013,77(11):2458-2461
Twenty-one naturally occurring flavonoids were tested for inhibitory activities against alpha-glucosidase (EC 3.2.1.20) and alpha-amylase (EC 3.2.1.1). Luteolin, amentoflavone, luteolin 7-O-glucoside, and daidzein were the strongest inhibitors among the compounds tested. Luteolin inhibited alpha-glucosidase by 36% at the concentration of 0.5 mg/ml and was stronger than acarbose, the most widely prescribed drug, in inhibitory potency, suggesting that it has the possibility to effectively suppress postprandial hyperglycemia in patients with non-insulin dependent diabetes mellitus. Luteolin also inhibited alpha-amylase effectively although it was less potent than acarbose. The clinical value of luteolin needs to be further evaluated. 相似文献
6.
The inhibition kinetics for isoacarbose (a pseudotetrasaccharide, IsoAca) and acarviosine-glucose (pseudotrisaccharide, AcvGlc), both of which are derivatives of acarbose, were investigated with various types of alpha-glucosidases obtained from microorganisms, plants, and insects. IsoAca and AcvGlc, competitive inhibitors, allowed classification of alpha-glucosidases into two groups. Enzymes of the first group were strongly inhibited by AcvGlc and weakly by IsoAca, in which the K(i) values of AcvGlc (0.35-3.0 microM) were 21- to 440-fold smaller than those of IsoAca. However, the second group of enzymes showed similar K(i) values, ranging from 1.6 to 8.0 microM for both compounds. This classification for alpha-glucosidases is in total agreement with that based on the similarity of their amino acid sequences (family I and family II). This indicated that the alpha-glucosidase families I and II could be clearly distinguished based on their inhibition kinetic data for IsoAca and AcvGlc. The two groups of alpha-glucosidases seemed to recognize distinctively the extra reducing-terminal glucose unit in IsoAca. 相似文献
7.
Rossi EJ Sim L Kuntz DA Hahn D Johnston BD Ghavami A Szczepina MG Kumar NS Sterchi EE Nichols BL Pinto BM Rose DR 《The FEBS journal》2006,273(12):2673-2683
Inhibitors targeting pancreatic alpha-amylase and intestinal alpha-glucosidases delay glucose production following digestion and are currently used in the treatment of Type II diabetes. Maltase-glucoamylase (MGA), a family 31 glycoside hydrolase, is an alpha-glucosidase anchored in the membrane of small intestinal epithelial cells responsible for the final step of mammalian starch digestion leading to the release of glucose. This paper reports the production and purification of active human recombinant MGA amino terminal catalytic domain (MGAnt) from two different eukaryotic cell culture systems. MGAnt overexpressed in Drosophila cells was of quality and quantity suitable for kinetic and inhibition studies as well as future structural studies. Inhibition of MGAnt was tested with a group of prospective alpha-glucosidase inhibitors modeled after salacinol, a naturally occurring alpha-glucosidase inhibitor, and acarbose, a currently prescribed antidiabetic agent. Four synthetic inhibitors that bind and inhibit MGAnt activity better than acarbose, and at comparable levels to salacinol, were found. The inhibitors are derivatives of salacinol that contain either a selenium atom in place of sulfur in the five-membered ring, or a longer polyhydroxylated, sulfated chain than salacinol. Six-membered ring derivatives of salacinol and compounds modeled after miglitol were much less effective as MGAnt inhibitors. These results provide information on the inhibitory profile of MGAnt that will guide the development of new compounds having antidiabetic activity. 相似文献
8.
Identification, cloning, expression, and characterization of the extracellular acarbose-modifying glycosyltransferase, AcbD, from Actinoplanes sp. strain SE50.
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M Hemker A Stratmann K Goeke W Schr?der J Lenz W Piepersberg H Pape 《Journal of bacteriology》2001,183(15):4484-4492
An extracellular enzyme activity in the culture supernatant of the acarbose producer Actinoplanes sp. strain SE50 catalyzes the transfer of the acarviosyl moiety of acarbose to malto-oligosaccharides. This acarviosyl transferase (ATase) is encoded by a gene, acbD, in the putative biosynthetic gene cluster for the alpha-glucosidase inhibitor acarbose. The acbD gene was cloned and heterologously produced in Streptomyces lividans TK23. The recombinant protein was analyzed by enzyme assays. The AcbD protein (724 amino acids) displays all of the features of extracellular alpha-glucosidases and/or transglycosylases of the alpha-amylase family and exhibits the highest similarities to several cyclodextrin glucanotransferases (CGTases). However, AcbD had neither alpha-amylase nor CGTase activity. The AcbD protein was purified to homogeneity, and it was identified by partial protein sequencing of tryptic peptides. AcbD had an apparent molecular mass of 76 kDa and an isoelectric point of 5.0 and required Ca(2+) ions for activity. The enzyme displayed maximal activity at 30 degrees C and between pH 6.2 and 6.9. The K(m) values of the ATase for acarbose (donor substrate) and maltose (acceptor substrate) are 0.65 and 0.96 mM, respectively. A wide range of additional donor and acceptor substrates were determined for the enzyme. Acceptors revealed a structural requirement for glucose-analogous structures conserving only the overall stereochemistry, except for the anomeric C atom, and the hydroxyl groups at positions 2, 3, and 4 of D-glucose. We discuss here the function of the enzyme in the extracellular formation of the series of acarbose-homologous compounds produced by Actinoplanes sp. strain SE50. 相似文献
9.
Baek JS Kim HY Abbott TP Moon TW Lee SB Park CS Park KH 《Bioscience, biotechnology, and biochemistry》2003,67(3):532-539
Simmondsin was modified with acarviosine-glucose using the transglycosylation activity of Thermus maltogenic amylase to synthesize a novel compound with both antiobesity and hypoglycemic activity. The LC/MS and 13C NMR analyses confirmed that the structure of the major transglycosylation product was acarviosine-simmondsin (Acv-simmondsin), in which acarviosine was attached to the glucose moiety of simmondsin by an alpha-(1,6)-glycosidic linkage. It was found that Acv-simmondsin was a potent competitive inhibitor of alpha-glucosidase with the Ki value of 0.69 microM and a mixed type inhibitor of alpha-amylase with the Ki and KI of 20.78 microM and 26.31 microM, respectively. The administration of Acv-simmondsin (0.1 g/100 g diet/day) to mice for 5 days significantly reduced food intake by 35%, compared to 25% with simmondsin in control obese mice. Acv-simmondsin (50 mg/kg BW) suppressed the postprandial blood glucose response to sucrose (1 g/kg BW) by 74%, compared to 71% with acarbose, in normal rats. 相似文献
10.
Numao S Damager I Li C Wrodnigg TM Begum A Overall CM Brayer GD Withers SG 《The Journal of biological chemistry》2004,279(46):48282-48291
A new approach for the discovery and subsequent structural elucidation of oligosaccharide-based inhibitors of alpha-amylases based upon autoglucosylation of known alpha-glucosidase inhibitors is presented. This concept, highly analogous to what is hypothesized to occur with acarbose, is demonstrated with the known alpha-glucosidase inhibitor, d-gluconohydroximino-1,5-lactam. This was transformed from an inhibitor of human pancreatic alpha-amylase with a K(i) value of 18 mm to a trisaccharide analogue with a K(i) value of 25 mum. The three-dimensional structure of this complex was determined by x-ray crystallography and represents the first such structure determined with this class of inhibitors in any alpha-glycosidase. This approach to the discovery and structural analysis of amylase inhibitors should be generally applicable to other endoglucosidases and readily adaptable to a high throughput format. 相似文献
11.
Alpha-glucosidase inhibitory activity of Syzygium cumini (Linn.) Skeels seed kernel in vitro and in Goto-Kakizaki (GK) rats 总被引:1,自引:0,他引:1
Shinde J Taldone T Barletta M Kunaparaju N Hu B Kumar S Placido J Zito SW 《Carbohydrate research》2008,343(7):1278-1281
Syzygium cumini seed kernel extracts were evaluated for the inhibition of alpha-glucosidase from mammalian (rat intestine), bacterial (Bacillus stearothermophilus), and yeast (Saccharomyces cerevisiae, baker's yeast). In vitro studies using the mammalian alpha-glucosidase from rat intestine showed the extracts to be more effective in inhibiting maltase when compared to the acarbose control. Since acarbose is inactive against both the bacterial and the yeast enzymes, the extracts were compared to 1-deoxynojirimycin. We found all extracts to be more potent against alpha-glucosidase derived from B. stearothermophilus than that against the enzymes from either baker's yeast or rat intestine. In an in vivo study using Goto-Kakizaki (GK) rats, the acetone extract was found to be a potent inhibitor of alpha-glucosidase hydrolysis of maltose when compared to untreated control animals. Therefore, these results point to the inhibition of alpha-glucosidase as a possible mechanism by which this herb acts as an anti-diabetic agent. 相似文献
12.
Some aspects of the mechanism of complexation of red kidney bean alpha-amylase inhibitor and alpha-amylase 总被引:2,自引:0,他引:2
Bovine pancreatic alpha-amylase binds 1 mol of acarbose (a carbohydrate alpha-amylase inhibitor) per mol at the active site and also binds acarbose nonspecifically. The red kidney bean alpha-amylase inhibitor-bovine pancreatic alpha-amylase complex retained nonspecific binding for acarbose only. Binding of p-nitrophenyl alpha-D-maltoside to the final complex of red kidney bean alpha-amylase inhibitor and bovine pancreatic alpha-amylase has a beta Ks (Ks') value that is 3.4-fold greater than the Ks (16 mM) of alpha-amylase for p-nitrophenyl alpha-D-maltoside alone. The initial complex of alpha-amylase and inhibitor apparently hydrolyzes this substrate as rapidly as alpha-amylase alone. The complex retains affinity for substrates and competitive inhibitors, which, when present in high concentrations, cause dissociation of the complex. Maltose (0.5 M), a competitive inhibitor of alpha-amylase, caused dissociation of the red kidney bean alpha-amylase inhibitor--alpha-amylase complex. Interaction between red kidney bean (Phaseolus vulgaris) alpha-amylase inhibitor and porcine pancreatic alpha-amylase proceeds through two steps. The first step has a Keq of 3.1 X 10(-5) M. The second step (unimolecular; first order) has a forward rate constant of 3.05 min-1 at pH 6.9 and 30 degrees C. alpha-Amylase inhibitor combines with alpha-amylase, in the presence of p-nitrophenyl alpha-D-maltoside, noncompetitively. On the basis of the data presented, it is likely that alpha-amylase is inactivated by the alpha-amylase inhibitor through a conformational change. A kinetic model, in the presence and absence of substrate, is described for noncompetitive, slow, tight-binding inhibitors that proceed through two steps. 相似文献
13.
Alpha-glucosidase inhibition from a Chinese medical herb (Ramulus mori) in normal and diabetic rats and mice 总被引:9,自引:0,他引:9
Alpha-glucosidase inhibitors are oral antidiabetic drugs. A traditional Chinese medical herb, Sangzhi (Ramulus mori), appears to have properties similar to those of alpha-glucosidase inhibitors. The effects of an aqueous extract of Shangzhi (SZ) were studied in normal and alloxan diabetic rats and mice, and these results compared with those for acarbose, an alpha-glucosidase inhibitor. In our grade-dose studies, SZ was found to lower and prolong the zenith of blood glucose concentration (ZBG) after sucrose or starch loading and stabilize blood glucose levels in fasting normal and alloxan diabetic mice. After 2 weeks of SZ administration with high-calorie chow or a normal diet, the fasting and non-fasting blood glucose concentrations in alloxan diabetic mice and rats were decreased. In alloxan rats, the blood fructosamine concentration was lowered. Results for acarbose and SZ were similar. These indicate that SZ has alpha-glucosidase inhibitory effects. 相似文献
14.
Lunina NA Berezina OV Veith B Zverlov VV Vorob'eva IP Chekanovskaia LA Khromov IS Raash G Libel' V Velikodvorskaia GA 《Molekuliarnaia biologiia》2003,37(5):810-819
The aglB and aglA genes from the starch/maltodextrin utilization gene cluster of Thermotoga neapolitana were subcloned into pQE vectors for expression in Escherichia coli. The recombinant proteins AglB and AglA were purified to homogeneity and characterized. Both enzymes are hyperthermostable, the highest activity was observed at 85 degrees C. AglB is an oligomer of identical 55-kDa subunits capable of aggregation. This protein hydrolyses cyclodextrins and linear maltodextrins to glucose and maltose by liberating glucose from the reducing end of the molecules, and it is a cyclodextrinase with alpha-glucosidase activity. The pseudo-tetrasaccharide acarbose, a potent alpha-amylase and alpha-glucosidase inhibitor, does not inhibit AglB but, on the contrary, acarbose is degraded quantitatively by AglB. Recombinant AglB is activated in the presence of CaCl2, KCl, and EDTA, as well as after heating of the enzyme. AglA is a dimer of two identical 54-kDa subunits, and it hydrolyses the alpha-glycoside bonds of disaccharides and short maltooligosaccharides, acting on the substrate from the non-reducing end of the chain. It is a cofactor-dependent alpha-glucosidase with a wide action range, hydrolysing both oligoglucosides and galactosides with alpha-link. Thereby, the enzyme is not specific with respect to the configuration at the C4 position of its substrate. For the enzyme to be active, the presence of NAD+, DTT, and Mn2+ is required. Enzymes AglB and AglA supplement one another in substrate specificity and ensure complete hydrolysis to glucose for the intermediate products of starch degradation. 相似文献
15.
The alpha-amylase (1, 4-alpha-d-glucanohydrolase; EC 3.2.1.1) and alpha-glucosidase (alpha-d-glucoside glucohydrolase; EC 3.2.1.20) secreted by Geobacillus thermodenitrificans HRO10 were purified to homogeneity (13.6-fold; 11.5% yield and 25.4-fold; 32.0% yield, respectively) through a series of steps. The molecular weight of alpha-amylase was 58kDa, as estimated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The alpha-amylase activity on potato starch was optimal at pH 5.5 and 80 degrees Celsius. In the presence of Ca(2+), the alpha-amylase had residual activity of more than 92% after 1h of incubation at 70 degrees Celsius. The alpha-amylase did not lose any activity in the presence of phytate (a selective alpha-amylase inhibitor) at concentrations as high as 10mM, rather it retained 90% maximal activity after 1h of incubation at 70 degrees Celsius. EGTA and EDTA were strong inhibitory substances of the enzyme. The alpha-amylase hydrolyzed soluble starch at 80 degrees Celsius, with a K(m) of 3.05mgml(-1) and a V(max) of 7.35Uml(-1). The molecular weight of alpha-glucosidase was approximately 45kDa, as determined by SDS-PAGE. The enzyme activity was optimal at pH 6.5-7.5 and 55 degrees Celsius. Phytate did not inhibit G. thermodenitrificans HRO10 alpha-glucosidase activity, whereas pCMB was a potent inhibitor of the enzyme. The alpha-glucosidase exhibited Michaelis-Menten kinetics with maltose at 55 degrees Celsius (K(m): 17mM; V(max): 23micromolmin(-1)mg(-1)). Thin-layer chromatography studies with G. thermodenitrificans HRO10 alpha-amylase and alpha-glucosidase showed an excellent synergistic action and did not reveal any transglycosylation catalyzed reaction by the alpha-glucosidase. 相似文献
16.
Synthesis of acarviosinyl-isomaltosyl-spiro-thiohydantoin in yields up to 20%, has been achieved by Bacillus stearothermophilus maltogenic amylase (BSMA). BSMA is capable of transferring the acarviosine-glucose residue from an acarbose donor onto glucopyranosylidene-spiro-thiohydantoin. Reactions were followed using HPLC and MALDI-TOF MS. 1H and 13C NMR studies revealed that the enzyme reserved its stereoselectivity. Glycosylation took place mainly at C-6 resulting in alpha-acarviosinyl-(1-->4)-alpha-D-glucopyranosyl-(1-->6)-D-glucopyranosylidene-spiro-thiohydantoin. This compound was found to be a much more efficient salivary amylase inhibitor than glucopyranosylidene-spiro-thiohydantoin with kinetic constants of K(EI)=0.19 microM and K(ESI)=0.24 microM. 相似文献
17.
Seo WD Kim JH Kang JE Ryu HW Curtis-Long MJ Lee HS Yang MS Park KH 《Bioorganic & medicinal chemistry letters》2005,15(24):5514-5516
Chalcones 1-20, a new class of glycosidase inhibitors, were synthesized, and their glycosidase inhibitory activities were investigated. Non-aminochalcones 1-12 had no inhibitory activity, however, aminochalcones 13-20 had strong glycosidase (alpha-glucosidase, alpha-amylase, and beta-amylase) inhibitory activities. In particular, sulfonamide chalcones 17-20 had more potent alpha-glucosidase inhibitory activity than aminated chalcone 13-16. 4'-(p-Toluenesulfonamide)-3,4-dihydroxy chalcone 20 (IC(50)=0.4microM) was the best inhibitor against alpha-glucosidase, and these sulfonamide chalcones showed non-competitive inhibition. 相似文献
18.
The SAR studies suggested that the C-ring of baicalein (1) was not necessary for the activity, and validated the importance of 2,3,4-trihydroxybenzoyl structure of 1. Thus, a series of 2,3,4-trihydroxybenzoyl-containing flavonoid analogs were investigated for the alpha-glucosidase inhibitory activity. The results indicated that 5,6,7-trihydroxy-2-phenyl-4-quinolone (2) and 5,6,7-trihydroxyflavanone (4) showed the comparable activity to 1, while 3,5,6,7-tetrahydroxyflavone (7), 5,6,7-trihydroxyisoflavone (8), and 6-hydroxygenistein (9) showed moderate alpha-glucosidase inhibitory activity. In addition, it was found that 6-amino-5,7-dihydroxyflavone (16) was a more potent and specific rat intestinal alpha-glucosidase inhibitor than 1, and showed the comparable activity to acarbose. This is the first report on mammalian intestinal alpha-glucosidase inhibitory activity of 6-aminoflavones. Kinetic studies revealed that 16 inhibited both sucrose- and maltose-hydrolyzing activities of rat intestinal alpha-glucosidase uncompetitively. 相似文献
19.
Four aminooligosaccharides were isolated and purified from the culture filtrate of Streptomyces coelicoflavus ZG0656. Their chemical structures were determined by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. The names acarviostatins I03, II03, III03, and IV03 were given to the oligomers due to their acarviosin core structures. Acarviostatins III03 and IV03, which contain three and four acarviosin-glucose moieties, respectively, were identified as novel compounds. The four acarviostatins were all mixed noncompetitive inhibitors of porcine pancreatic alpha-amylase (PPA). The inhibition constants (K(i)) for acarviostatins III03 and IV03 were 0.008 and 0.033muM, respectively. Acarviostatin III03 is the most effective alpha-amylase inhibitor known to date, with a K(i) value 260 times more potent than acarbose. 相似文献
20.
Enç FY Imeryüz N Akin L Turoğlu T Dede F Haklar G Tekeşin N Bekiroğlu N Yeğen BC Rehfeld JF Holst JJ Ulusoy NB 《American journal of physiology. Gastrointestinal and liver physiology》2001,281(3):G752-G763
We investigated the effect of acarbose, an alpha-glucosidase and pancreatic alpha-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 (r = 0.68, P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles. 相似文献