Α-glycosidase Inhibitors Research Articles

Pharmacokinetic mechanism of enhancement by Radix Pueraria flavonoids on the hyperglycemic effects of Cortex Mori extract in rats

Ethnopharmacological relevanceDiabetes mellitus, characterized by abnormal blood glucose evaluation, is a serious chronic disease. In the treatment of the disease, α-glycosidase inhibitors play an important role for controlling the postprandial blood glucose level. Cortex Mori, a traditional Chinese herbal medicine, has a long history of use for the treatment of headaches, cough, edema and diabetes. Modern pharmacological studies have shown that the herb has beneficial effects on the suppression of postprandial blood glucose levels by inhibiting α-glycosidase activity in the small intestine. 1-Deoxynojirimycin (DNJ), the main active ingredient of this herb, is recognized as a potent α-glycosidase inhibitor. Our previous studies have shown that the hypoglycemic effect of Cortex Mori extract (CME) was significantly improved when giving CME in combination with Radix Pueraria flavonoids (RPF). In the present study, the pharmacokinetics and intestinal permeability of DNJ were comparatively investigated in rats after being given orally or by intestinal perfusion with CME alone or in CME–RPF pairs, to explore the mechanism of this synergistic effect. Materials and methodsThe role of RPF on the plasma and urine concentrations of DNJ from CME orally administered was investigated. Four groups of rats received a single oral dose of either CME or CME–RPF, at DNJ equivalent doses of 20 and 40mg/kg, respectively. After dosing, plasma and urine were collected and assayed by LC/MS/MS. In addition, another two groups of rats were used for small intestinal perfusion with CME or CME–RPF at DNJ concentration of 10µM. ResultsCompared to the data when dosing with CME alone, the Cmax of DNJ were decreased from 5.78 to 2.94µg/ml (p<0.05) and 10.66 to 5.35µg/ml (p<0.01); Tmax were delayed from 0.40 to 0.55h and 0.35 to 0.50h (p<0.05); and MRT were significantly prolonged from 1.14 to 1.72h (p<0.05) and 0.95 to 1.62h (p<0.01), after dosing with CME–RPF at DNJ doses of 20 and 40mg/kg, respectively. In addition, the urinary recovery of DNJ over the first 4h after dosing significantly decreased from 48.76% to 33.86%. Effective permeability (Peff) of DNJ was decreased from 7.53×10−3 to 3.09×10−3cm/s (p<0.05) when RPF was added to CME, when it was evaluated using the rat intestinal perfusion model. ConclusionsAll the above results demonstrate that RPF was able to suspend and delay the absorption of DNJ, but did not affect the total amount of DNJ in the body. The resulting higher concentration of DNJ in the small intestine produced a relatively stronger effect of depressing the elevation of the postprandial blood glucose level. These findings support the important role of RPF in the application of CME on blood glucose control.

A new series of N2-substituted-5-(p-toluenesulfonylamino)phthalimide analogues as α-glucosidase inhibitors

Several members of a new family of non-sugar-type α-glycosidase inhibitors, bearing a 5-(p-toluenesulfonylamino)phthalimide moiety and various substituent at the N2 position, were synthesized and their activities were investigated. The newly synthesized compounds displayed different inhibition profile towards yeast α-glycosidase and rat intestinal α-glycosidase. Almost all the compounds had strong inhibitory activities against yeast α-glycosidase. Regarding rat intestinal α-glycosidase, only analogs with N2-aromatic substituents displayed varying degrees of inhibitory activities on rat intestinal maltase and lactase and nearly all compounds showed no inhibition against rat intestinal α-amylase. Structure–activity relationship studies indicated that 5-(p-toluenesulfonylamino)phthalimide moiety is a favorable scaffold to exert the α-glucosidase inhibitory activity and substituents at the N2 position have considerable influence on the efficacy of the inhibition activities.

Leprechaunism (Donohue syndrome): A case bearing novel compound heterozygous mutations in the insulin receptor gene

Leprechaunism (Donohue syndrome) is the most severe type of insulin receptor (INSR) gene anomaly with the majority of patients surviving for only 2 years. We report a surviving 2 -year-old male with leprechaunism, bearing novel compound heterozygous mutations in the INSR. The patient is a Japanese boy with acanthosis nigricans, lack of subcutaneous fat, hirsutism, thick lips, gum hypertrophy and extremely high insulin levels (6702 mU/mL). He was as having identified novel compound heterozygous mutations in INSR (p.T910M and p. E1047K). At 24 day-old, recombinant human insulin-like growth factor 1 (rh-IGF1) treatment was started because of poor weight gain. At 2 years old, the patient's serum glucose level and HbA1C value had worsened, and both a bolus of rh-IGF-1 and a subcutaneous injection of a rapid-acting insulin analog after meals, in addition to α-glycosidase inhibitor, were initiated from 2 years onward. Oxygen administration and biphasic positive airway pressure treatment were also initiated from 2 years old due to upper airway obstruction with adenoidal hypertrophy. In the experiments conducted using COS7 cells homozygously transfected with the INSR mutation, T910M INSR failed to process the proreceptor and decreased insulin-stimulated tyrosine phosphorylation. E1047K INSR resulted in a complete absence of insulin-stimulated tyrosine phosphorylation. These findings suggest the near absence of INSR in this patient. We consider that the rhIGF1 treatment contributed to his long survival, but it was not able to prevent his diabetic condition. Our report provides important insights into the function of INSR, and for the treatment of leprechaunism.

Production of the α-glycosidase inhibitor 1-deoxynojirimycin from Bacillus species

1-Deoxynojirimycin (DNJ), a potent α-glycosidase inhibitor, has therapeutic applications in treatments of HIV, Gaucher’s disease, and diabetes. DNJ has been extracted from natural sources (mulberry leaves) for therapeutic purposes; however, DNJ ingredients are in limited supply and are costly to obtain on a large scale. Since certain strains of Bacillus and Streptomyces species reportedly produce DNJ, they may serve as potential sources for high-yield DNJ production. In this study, we obtained evidence for a DNJ production in Bacillus subtilis DSM704 by hydrophilic interaction chromatography-tandem mass spectrometry. In addition, from a screen of 750 microorganisms, we identified additional Bacillus strains (Bacillus amyloliquefaciens AS385 and Bacillus subtilis B4) that produce DNJ in large quantities. Investigation of the effect of various culture conditions, using Bacillus subtilis DSM704 and the DNJ high-production Bacillus strains, provided evidence for the importance of sorbitol supplementation on the yield of the DNJ precursor, 2-amino-2-deoxy-D-mannitol, thereby increasing DNJ production. The role of sorbitol in increased DNJ production was supported by an observed increase in mRNA expression of the biosynthetic gene, gabT1. When Bacillus amyloliquefaciens AS385 was cultured in medium supplemented with sorbitol, extracellular DNJ concentration reached a maximum of 460mg/l of medium (equivalent to 9.20mg/g of freeze-dried medium), indicating that this strain can serve as a source for food- and drug-grade products. These findings not only lead to a further understanding of the DNJ biosynthetic pathway, but also suggest a method for microbial mass production of DNJ for therapeutic applications.

Miglitol, α-glycosidase inhibitor, reduces visceral fat accumulation and cardiovascular risk factors in subjects with the metabolic syndrome: A randomized comparable study

Background/objectivesVisceral fat obesity plays an essential role in the clustering of cardiovascular risk factors. This study aimed to clarify the effects of miglitol, α-glycosidase inhibitor, on body weight, fat distribution and cardiovascular risk factors in patients with the metabolic syndrome. Methods and resultsOne hundred and eleven drug naive patients with the metabolic syndrome were continuously recruited and randomly allocated to a group of life style modification (LSM) alone or a group of LSM with miglitol per os 50mg×3 (LSM+miglitol). After 12weeks of treatment, body weight (5.1%), body mass index (4.9%) and waist circumference were greatly reduced in miglitol group (n=42) than in LSM group (n=43). Plasma levels of insulin and glucose during an oral 75g glucose loading were decreased only in miglitol group. Visceral fat area, determined by abdominal computed tomography, was greatly reduced in miglitol group (baseline 188 vs 12weeks 161cm2, p<0.0001) than in LSM group (184 vs 174cm2, p<0.05). Subcutaneous fat area was reduced only in miglitol group (p<0.001). Systolic blood pressure was reduced in miglitol group (142 vs 133mm Hg, p<0.001), but not in control group (137 vs 134mm Hg). Serum levels of triglyceride, LDL-cholesterol, γ-GTP, and high-sensitive CRP were decreased and adiponectin was increased only in miglitol group. ConclusionsOur results indicated that miglitol showed an anti-obesity potential, which was achieved by reducing abdominal fat accumulation and/or enhanced insulin requirement, and then corrected both the metabolic and hemodynamic aberrations seen in patients with the metabolic syndrome (UMIN Clinical Trial Registry UMIN000007650).

A novel gelatin crosslinking method retards release of mulberry 1-deoxynojirimycin providing a prolonged hypoglycaemic effect

Mulberry 1-deoxynojirimycin (DNJ), a potent α-glycosidase inhibitor, has therapeutic potency in the suppression of postprandial blood glucose levels thereby possibly preventing diabetes mellitus. However, DNJ has a relatively short half-life in vivo (about 2 h). Therefore, several doses of mulberry DNJ are required to achieve optimal therapeutic results. This study aimed to delay the release of mulberry DNJ with biodegradable matrices to maintain the intestinal DNJ concentration and prolong the hypoglycaemic effect in vivo. A novel, simple, and commercially viable method was adopted to develop DNJ-entrapped microspheres (DNJ-MSs). A higher extent of crosslinking and the larger sized DNJ-MS decreased the rate of mulberry DNJ release in vitro. Consequently, an in vivo study was performed in Wistar rats over a 6 h period. The area under curve (AUC) of rats with DNJ-MS was significantly increased, compared to animals dosed with mulberry powder (control). DNJ-MS suppressed postprandial glucose from sucrose administration at the initial and 3 h time points indicating a prolonged hypoglycaemic effect.

Pharmacodynamic comparison of two formulations of Acarbose 100-mg tablets

Acarbose, an α-glycosidase inhibitor, is used to treat diabetic patients. Pharmacokinetic evaluation of acarbose is difficult because <2% is absorbed systemically. The current investigation evaluated the bioequivalence of two formulations of acarbose through pharmacodynamic comparison. This investigation consisted of a pilot study and a main study. The pilot study had an open, single-dose, single-sequence design. Subjects received placebo and then two tablets of reference formulation (Glucobay(®) 100 mg tablet; Bayer Healthcare) on two consecutive days with sucrose. The main study was an open, randomized, two-period, two-sequence crossover study. Subjects randomly received placebo and two tablets of either test formulation (generic acarbose 100-mg tablet) or reference formulation with sucrose on two consecutive days in the first period. In the second period, placebo and alternative formulation were administered. Serial blood samples for pharmacodynamic assessment were taken after each administration. The maximum serum glucose concentration (G(max)) and the area under the serum glucose concentration-time profile (AUC(gluc)) were determined and compared. Five subjects completed the pilot study. The AUC(gluc) from dosing until 1 h post-dose (AUC(gluc,1 h)) was significantly different between the placebo and acarbose. A total of 33 subjects completed the main study. The mean differences in G(max) (ΔG(max)) and AUC(gluc,1 h) (ΔAUC(gluc,1 h)) for the reference formulation compared with placebo were 22·0 ± 18·3 mg/dL and 928·2 ± 756·0 mg min/dL, respectively. The corresponding values for the test formulation were 23·3 ± 21·2 mg/dL and 923·0 ± 991·4 0 mg min/dL, respectively. The geometric mean ratios (GMRs) of the test formulation to the reference formulation for ΔG(max) and ΔAUC(gluc, 1 h) were 1·06 and 1·00, respectively, and the 90% confidence intervals (CIs) corresponding values were 0·79-1·39 and 0·64-1·36, respectively. The 90% CIs of GMRs for the pharmacodynamic parameters chosen for bioequivalence evaluation of two formulations of acarbose did not meet the commonly accepted regulatory criteria for bioequivalence (0·80-1·25).

The efficacy and safety of vildagliptin in patients with type 2 diabetes: a meta-analysis of randomized clinical trials

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a relatively new class of drugs for the management of type 2 diabetes (T2DM). Vildagliptin is an oral DPP-4 inhibitor approved in more than 70 countries. The purpose of this meta-analysis is to provide an update on the clinical efficacy and safety of vildagliptin in patients with T2DM. A literature search identified 30 randomized controlled trials comparing vildagliptin with comparators (placebo or other hypoglycaemic agents). Meta-analyses were conducted for HbA1c, weight, fasting plasma glucose (FPG), hypoglycaemia and other adverse events. The outcomes of HbA1c, weight and FPG were analysed as weighted mean differences (WMD), and the number of ADRs events as relative risks (RR). Compared with placebo, vildagliptin lowered HbA1c {WMD, -0·77% [95% confidence interval (CI), -0·96% to -0·58%] for 100 mg/day of vildagliptin and -0·58% [95% CI, -0·72% to -0·44%] for 50 mg/day of vildagliptin}. The effect was non-inferior to thiazolidinediones, sulfonylureas and α-glycosidase inhibitors, but inferior to metformin. Compared with placebo, treatment with 50 mg/day of vildagliptin caused neutral weight changes, while 100 mg/day of vildagliptin resulted in slight weight gain [0·95 kg (95% CI, 0·73-1·17 kg)]. In addition, compared to comparators, vildagliptin was not associated with an increase in overall risk for any adverse events [RR, 0·97 (95% CI, 0·94-0·99)]. The incidence of hypoglycaemia was low with vildagliptin, and the risk with vildagliptin was not significantly different from the comparators [0·85 (95% CI, 0·49-1·47)]. The use of vildagliptin did not display any increased risks of infection [1·03 (95% CI, 0·94-1·13) for nasopharyngitis and 1·07 (95% CI, 0·90-1·27) for upper respiratory tract infection]. Vildagliptin is effective in glycaemic control with a low risk of hypoglycaemia and other adverse reactions. This may have an important impact on patient adherence to this medication.

Advances in the Synthesis of Homochiral (−)-1-Azafagomine and (+)-5-epi-1-Azafagomine. 1-N-Phenyl Carboxamide Derivatives of both Enantiomers of 1-Azafagomine: Leads for the Synthesis of Active α-Glycosidase Inhibitors.

A new expeditious preparation of homochiral (-)-1-azafagomine and (+)-5-epi-1-azafagomine has been devised. Stoodley's diastereoselective cycloaddition of dienes bearing a 2,3,4,6-tetraacetyl glucosyl chiral auxiliary to 4-phenyl-1,2,4-triazole-3,5-dione was merged with Bols's protocol for functionalizing alkenes into molecules bearing a glucosyl framework. Homochiral (+)-5-epi-1-azafagomine was synthetized for the first time. Partial reductive cleavage of the phenyltriazolidinone moiety afforded new homochiral 1-N-phenyl carboxamide derivatives of 1-azafagomine. Both enantiomers of these derivatives were synthetized and tested, displaying a very good enzymatic inhibition toward baker's yeast α-glucosidase. The molecular recognition mechanism of the 1-N-phenyl carboxamide derivative of 1-azafagomine by α-glucosidase from baker's yeast was studied by molecular modeling. The efficient packing of the aromatic ring of the 1-N-phenyl carboxamide moiety into a hydrophobic subsite (pocket) in the enzyme's active site seems to be responsible for the improved binding affinity in relation to underivatized (-)-1-azafagomine and (+)-1-azafagomine.

Amplification of the Inhibitory Activity and Reversal of the Selectivity of Miglitol by C(2′)‐Monofluorination

Selective monofluorination of the α-glycosidase inhibitor and antidiabetic agent miglitol at positions C(2') or C(6) creates competitive inhibitors of glycosidases. Introducing a fluorine substituent at position C(6) results in a reduced binding to the enzyme whereas fluorination at C(2') produces an inhibitor with an activity four times higher than the parent compound. This compound is selective for the α-galactosidase from green coffee beans. Its screening against a panel of human cell lines showed a low cytotoxicity, therefore, making this compound an interesting candidate for further clinical investigations.

Determination of iminosugars in mulberry leaves and silkworms using hydrophilic interaction chromatography–tandem mass spectrometry

Mulberry 1-deoxynojirimycin (DNJ, a potent α-glycosidase inhibitor) has been investigated thoroughly for its analytical methods and therapeutic potential against diabetes, whereas little attention has been given to other iminosugars such as 2- O-α- d-galactopyranosyl–DNJ (GAL–DNJ) and fagomine. For instance, concentration and composition of these iminosugars in mulberry leaves as well as sericulture products have not been fully characterized due to lack of suitable analytical methods. Here we developed a simultaneous determination method for DNJ, GAL–DNJ, and fagomine using hydrophilic interaction chromatography (HILIC) with tandem mass spectrometry (MS/MS). When mulberry leaf extracts were subjected to HILIC–MS/MS with multiple reaction monitoring (MRM), individual iminosugars could be separated and detected. The developed method is sufficiently sensitive for determining iminosugars in mulberry leaves as well as silkworms, providing new information (e.g., different amounts of iminosugars in mulberry leaf varieties; high DNJ and low GAL–DNJ in the silkworm body, especially in the blood) that is useful for producing iminosugar-rich products for nutraceutical purposes.

Optimization of 1-Deoxynojirimycin Extraction from Mulberry Leaves by Using Response Surface Methodology

Mulberry 1-deoxynojirimycin (DNJ, a potent alpha-glycosidase inhibitor) has therapeutic potency against diabetes mellitus. However, the amount of DNJ in mulberry leaves is low (about 0.1%), and a more effective extraction method is needed. Ultrasound-assisted extraction (UAE) was applied in this study for mulberry DNJ extraction, and five factors, the percentage of ethanol in the extraction solvent (x(1)), ratio of the extraction solvent to mulberry sample (x(2)), ultrasonic power (x(3)), extraction temperature (x(4)) and extraction time (x(5)), were investigated by fractional factorial 2((5-1)) design (FFD) to obtain the optimum extraction efficiency (DNJ yield, Y(1)) and extraction productivity (total yield, Y(2)). The results showed that x(2), x(3) and x(5) had significant impact on Y(1) and Y(2), and were further optimized by response surface methodology (RSM). Under the optimized conditions (x(2), x(3) and x(5) of 7 ml/g, 180 W and 260 s, respectively), DNJ-enriched powder (0.8%) was produced with high extraction efficiency (98%) and productivity (20%), enabling this product to be used for nutraceutical purposes.

Amplification of the inhibitory activity of miglitol by monofluorination

Selective monofluorination of the α-glycosidase inhibitor and antidiabetic agent Miglitol at position C(2) creates an competitive inhibitor of five times higher activity than the parent compound. Its screening against a panel of human cell lines showed a low cytotoxicity therefore making this compound an interesting candidate for further clinical investigations.

Incretins: pathophysiological and therapeutic implications of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1

Incretins such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are intestinal postprandial hormones that stimulate insulin release from the pancreas as long as circulating glucose concentrations are raised....

Effects of in vivo antioxidant enzyme activities of myrtle oil in normoglycaemic and alloxan diabetic rabbits

In this study we aimed to evaluate the in vivo effects of myrtle oil (myrtii oleum) on the antioxidant enzymes such as superoxide dismutase and catalase, the levels of malondialdehyde in liver tissues as an index of lipid peroxidation and nitrite–nitrate levels in normoglycaemic and alloxan-induced diabetic and MO-treated rabbits. In our previous study, we assumed that MO with a dose of 50 mg/kg, possesses a hypoglycemic activity and this activity was independent from the effects of insulin. Myrtle oil exerts its hypoglycemic activity by enhanced glycolysis, glycogenesis and decreased glycogenolysis. What is more glucose load data strongly suggest that MO treatment produces hypoglycemia mainly by reducing intestinal absorption of glucose, so MO could be an α-glycosidase enzyme inhibitor which had a hypoglycaemic effect only on alloxan-induced diabetic rabbits on the fourth hour and on orally glucose loaded group. The major finding of this new study is that, MO may not offer any protection against oxidative stress during acute studies in normoglycemic and diabetic groups. Although the levels of superoxide dismutase and catalase enzyme activities did not change during acute studies in diabetes + MO group, there was a significant change at the end of 21 days. There is a very limited knowledge about MO and its effects on diabetes. Therefore, we tried to explain the mechanism that might underlie the protective effects of MO with this paper.

Biological evaluation of de-O-sulfonated analogs of salacinol, the role of sulfate anion in the side chain on the α-glucosidase inhibitory activity

De-O-sulfonated analogs ( 10a, Y − = CH 3OSO 3 and 10b, Y − = Cl) of salacinol, a naturally occurring glycosidase inhibitor, and its diastereomer ( 12a, Y − = CH 3OSO 3) with l-thiosugar moiety (1,4-dideoxy-1,4-epithio- l-arabinitol) were prepared. Their inhibitory activities against intestinal maltase and sucrase were examined and compared with those of the parent α-glycosidase inhibitor, salacinol ( 1a). Compounds 10a and 10b showed a potent inhibitory activity equal to that of 1a against both enzymes, although 12a was a weak inhibitor against sucrase and maltase. These results indicated that the O-sulfonate anion moiety of 1a is not essential for the inhibitory activity.

Antiviral effects of glycosylation and glucose trimming inhibitors on human parainfluenza virus type 3

Endoplasmic reticulum (ER) α-glucosidase inhibitors block the trimming of N-linked glycosylation and thus prevent the production of several viruses. The present study investigates the antiviral effects of the α-glucosidase and α-mannosidase inhibitors (castanospermine, 1-deoxynojirimycin, bromoconduritol, deoxymannojirimycin and swainsonine) on human parainfluenza virus type 3 (HPIV3). The α-glucosidase inhibitors (castanospermine, 1-deoxynojirimycin) in recombinant expression systems reduced the surface and intracellular expression of both HPIV3 F and HN proteins. On the other hand, α-mannosidase inhibitors prevented processing of the oligosaccharides on HPIV3 glycoproteins into the complex form. Consequently, α-glycosidase inhibitors (castanospermine and 1-deoxynojirimycin) significantly inhibited viral fusion activity. We demonstrated that the α-glucosidase inhibitors (castanospermine and 1-deoxynojirimycin) reduced the infectivity of newly released viral particles. We postulate that α-glucosidase inhibitors can prevent the first steps of HPIV3 envelope glycoprotein processing and that the inhibition of glucose trimming has antiviral effects.

肥満・インスリン抵抗性を示す２型糖尿病患者におけるメトホルミン使用に関する研究

To examine the effectiveness of metformin (Met) in combination with sulfonylurea (SU) or α-glycosidase inhibitor (α-GI) or both SU and α-GI, 120 type 2 diabetes mellitus with obesity and insulin resistance have been included in a prospective study at both outpatient and inpatient clinics at Tokyo Metropolitan Futyu Hospital. Met treatment of 500mg or 750mg/day was administered in all groups.A significant reduction in the hemoglobin A 1c levels along with improvements in the insulin resistant index were observed for the α-GI + Met group after 6 months, and also for the Met monotherapy, SU+ Met and SU+α-GI+Met groups after 12months. Only 7 patients showed transitional adoversed effects such as gastrointestinal symptoms (nausea and vomiting), but no patient experienced lactic acidosis.In conclusion, 1) as indicated in the Japanese medication insert, the effectiveness of Met in combination use with SU was confirmed in patients previously found to be poorly controlled with SU monotherapy. In addition, the effectiveness of the non-indicated use of Met was also suggested under the following two conditions : 2) Met monotherapy in type 2 diabetes mellitus who did not respond to diet therapy was also effective ; 3) The addition of Met is also effective in patients whose glucose levels were previously poorly controlled with bothα-GI and α-GI + SU. Further study is necessary to increase the adoptions for Japanese medication inserts for type 2 diabetes mellitus patients.

アカルボースとボクリボースの臨床的効果の比較 アカルボースからボクリボースに処方変更された症例での調査

Several years have passed since α-glycosidase inhibitors entered the market as antidiabetics. At present, acarbose and voglibose are the only drugs in this category that are available in Japan. Although several studies have been perfomed on the efficacy and side effects of these drugs, the results are still not uniform. In this study, changes in the laboratory data were investigated in patients treated at our department in whom their medication was changed from acarbose to voglibose. The subjects consisted of 11 outpatients with non-insulin-dependent diabetes mellitus (NIDDM) in whom their medication was changed from 300 mg of acarbose to 0.6 mg of voglibose without any alterations in concomitant drugs.No significant changes were noted in the HbAic, TG, TC, or HDL-C levels at 16 weeks after the change in medication. In addition, no abnormal data were observed in the GOT, GPT, γ-GTP, ALP, or K levels in patients before or after the change in medication. An interview study showed no remarkable changes in the symptoms except for a decreased frequency of flatus after the change in medication from acarbose to voglibose. The above results suggested that 0.6 mg of voglibose was superior in terms of QOL to 300 mg of acarbose because of a lower incidence of gastrointestinal symptoms, although the hypoglycemic effect was comparable between the 2 drugs.Additional studies should be performed in a larger number of patients to obtain more reliable results.

A flexible and efficient synthesis of the pyrrolidine α-glycosidase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB-1)

The α-glucosidase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB-1) 8 is synthesised in ten steps from D-serine with an overall yield of 49%; the key step of this synthesis makes use of the readily prepared serine-derived α-dibenzylamino aldehyde 3 in a highly diastereoselective glycolate aldol reaction.