Acarbose, a potent α-glucosidase inhibitor, is widely used as an oral anti-diabetic drug for the treatment of the type 2, non-insulin-dependent diabetes. In this work, a gel type strong acid cation exchange resin 001...Acarbose, a potent α-glucosidase inhibitor, is widely used as an oral anti-diabetic drug for the treatment of the type 2, non-insulin-dependent diabetes. In this work, a gel type strong acid cation exchange resin 001×4 was applied to isolate acarbose from fermentation broth. It was demonstrated that cation exchanger 001×4 displayed a large adsorption capacity and quick exchange rate for acarbose. The static adsorption equilibrium data were well fitted to the Langmuir equation. Column adsorption experiments demonstrated that high dynamic adsorption capacity was reached at bed height of 104.4 mm, feed flow rate of 1.0 ml·min 1and acarbose concentration of 4.0 mg·ml 1.Under the optimized conditions, the column chromatography packed with cation exchanger 001×4 recovered 74.3%(by mass) of acarbose from Actinoplanes utahensis ZJB-08196 fermentation broth with purity of 80.1%(by mass),demonstrating great potential in the practical applications in acarbose separation.展开更多
AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved b...AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS: The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS: The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P 【0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION: There are augmented effects of acarbose and GA,which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination.展开更多
Acarbose is an agent that has been used to treat type 2 diabetes for about 30 years;it prevents postprandial hyperglycemia by inhibiting carbohydrate digestion in the small intestine.Since incretin-based treatments ha...Acarbose is an agent that has been used to treat type 2 diabetes for about 30 years;it prevents postprandial hyperglycemia by inhibiting carbohydrate digestion in the small intestine.Since incretin-based treatments have been preferred over the last 10 to 15 years,the use of acarbose is not as common in treating type 2 diabetes as before.Some studies have shown that acarbose also produces a weight-loss effect by increasing glucagon-like peptide 1(GLP-1).The positive effect of acarbose on GLP-1,and increasing evidence that it provides cardiovascular protection,suggests that acarbose may again be considered among the first-choice antidiabetic agents,as it was in the 1990s.展开更多
BACKGROUND The waist-to-height ratio(WHtR)is a promising anthropometric measure used to evaluate cardiovascular risk in diabetes and metabolic syndrome patients.The metformin and acarbose in Chinese as the initial hyp...BACKGROUND The waist-to-height ratio(WHtR)is a promising anthropometric measure used to evaluate cardiovascular risk in diabetes and metabolic syndrome patients.The metformin and acarbose in Chinese as the initial hypoglycaemic treatment trial demonstrated that acarbose and metformin reduced the WHtR after 24 wk of treatment.AIM To investigate the factors associated with a decrease in the WHtR in newly diagnosed Chinese type 2 diabetes patients receiving acarbose or metformin monotherapy.METHODS At 24 wk,343 patients in the acarbose treatment and 333 patients in the metformin treatment were included in this analysis.On the basis of the reduction in the WHtR,these participants were divided into the following two groups:LowΔWHtR group and highΔWHtR group.Metabolic and related parameters associated with a highΔWHtR were investigated using univariate and multivariate logistic regression analyses.RESULTS A significant decrease in the WHtR was observed in both treatment groups(acarbose:-0.015,95%confidence interval[CI]:-0.018 to-0.012,P<0.001;metformin:-0.013,95%CI:-0.016 to-0.010,P<0.001).In both the acarbose and metformin groups,the WHtR of the women was more likely to be reduced than that of the men.In the acarbose group,a lower baseline area under the curve of glucagon-like peptide 1(AUCGLP-1)was associated with a highΔWHtR(odds ratio[OR]=0.796,P<0.001),while a higher baseline AUCGLP-1 was associated with a highΔWHtR in the patients treated with metformin(OR=1.133,P=0.025).Regarding the changes from baseline,an increase in AUCGLP-1 was associated with a highΔWHtR in the acarbose(OR=1.121,P=0.016)but not metformin group.A higher reduction in high-density lipoprotein cholesterol/non-highdensity lipoprotein cholesterol was also associated with a highΔWHtR in the acarbose arm(OR=20.735,P=0.001).In the metformin arm,a higher reduction in fasting plasma glucose(OR=0.843,P=0.039)and total cholesterol was associated with a highΔWHtR(OR=0.743,P=0.013).CONCLUSION A lower glucagon-like peptide 1 level and higher increase in glucagon-like peptide 1 are associated with a high reduction in the WHtR in newly diagnosed Chinese diabetes patients receiving treatment with acarbose.展开更多
Objective:To discuss the effect of the combined therapy of levemir and acarbose on T cell subsets and function of isletβ cells in elder patients with early-onset type 2 Diabetes Mellitus. Methods:According to the num...Objective:To discuss the effect of the combined therapy of levemir and acarbose on T cell subsets and function of isletβ cells in elder patients with early-onset type 2 Diabetes Mellitus. Methods:According to the number parity of entry sequence, 100 cases of elder patients with early-onset type 2 Diabetes Mellitus are divided into the control group and the observation group of 50 cases. The control group was treated with novolin and acarbose, the observation group was given subcutaneous injection of levemir and acarbose treatment. Compare the T cell subsets and function of isletβ cells in two group of patients before the treatment (T0), treatment for 4 weeks (T1) ,treatment for 8 weeks (T2).Results:(1) The levels of T0, T1, T2CD3+, CD4+, CD4+/CD8+ were increased in both groups, and CD8+ decreased. Among them, the levels of T1, T2CD3+, CD4+, CD4+/CD8+ of the observation group were obviously higher than the control group, the level of CD8+ was lowly than the control group, the difference was statistically significant;(2) In the stage of T0, T1, T2, the levels of FPG, HbA1c, HOMA-IR were showed a downward trend, the levels of FIns, HOMA-B were increased. In these two groups, the levels of T1, T2FPG, HbA1c, HOMA-IR of the observation group were lower than the control group, and the levels of FIns, HOMA-B were higher than the control group, the difference was statistically significant;(3) In the control group occurred 3 cases of hypoglycemia, and the incidence of adverse reactions was 6%. However, in the observation group no occurred adverse reactions, the difference was statistically significant.Conclusions:The combined therapy of levemir and acarbose in elder patients with early-onset type 2 Diabetes Mellitus, It helps to improve immune function, protect the isletβ-cell function.展开更多
Objectives: To investigate the effects of insulin resistance on serum androgen level and ovulation of women with polycystic ovary syndrome (PCOS) and observe clinic role of acarbose in the treatment of hyperinsulinemi...Objectives: To investigate the effects of insulin resistance on serum androgen level and ovulation of women with polycystic ovary syndrome (PCOS) and observe clinic role of acarbose in the treatment of hyperinsulinemia, postprandial hyperglycemia and anovulation. Methods: 14 women accompanied by postprandial hyperglycemia with PCOS were administrated by acarbose for 12 weeks.14 age-matched individuals who had similar body mass index and normal menstruation were served as controls. Results: Serum T levels declined significantly from 4.09±1.04 nmol/L to 1.71±0.54 nmol/L (P<0.001), after acarbose treatment for 12 weeks. 12 out of 14 cases restored ovulation and menstrual cycles after acarbose treatment, among which 4 got pregnant. Conclusion: Acarbose may play a role on reducing postprandial hyperglycemia and HbAic levels, increase ISI and FSG/FI, indirectly reduce serum androgen levels through reducing plasma insulin level and recover ovarian ovulation in PCOS women with postprandial hyperglycemia.展开更多
Acarbose is used to control postpran-dial blood glucose in patients with type 2 diabetes and impaired glucose tolerance,since it improves insulin resistance and reduces blood lipids and cardiovascular complications.Ho...Acarbose is used to control postpran-dial blood glucose in patients with type 2 diabetes and impaired glucose tolerance,since it improves insulin resistance and reduces blood lipids and cardiovascular complications.However,in recent years,many studies have found that acarbose can mediate and regulate a variety of neurotransmitter-related diseases,although the mechanisms are not clear.Therefore,this paper analyzes the clinical effect of acarbose and its mediating effect on neurotransmitters of mental disorders through insulin,braingut axis,and calorie restriction,to provide a reference for the new clinical applications of acarbose.展开更多
Objective: to analyze the application value of metformin combined with acarbose in the treatment of type 2 diabetes. Methods: we selected 100 recently admitted patients with type 2 diabetes, the control group adopted ...Objective: to analyze the application value of metformin combined with acarbose in the treatment of type 2 diabetes. Methods: we selected 100 recently admitted patients with type 2 diabetes, the control group adopted the existing treatment method centered on metformin, and the experimental group adopted the acarbose treatment based on metformin. The relationship between the time required for glycosylated hemoglobin to reach the standard and the effective cure rate between the two patient groups. Results: after the observation, it can be found that the experimental group adopts the combined treatment, the blood sugar and insulin resistance are more effective when reaching the standard, and the total effective rate of the treatment is higher than that of the control group. Conclusion: it can be concluded that the combination therapy of metformin and acarbose has a good effect on the treatment of type 2 diabetes. It has an obvious effect on the clinical treatment of diabetes and the reduction of blood sugar, and is worthy of promotion.展开更多
Objective: to investigate the clinical effects of glargine and acarbose tablet in the treatment of senile diabetes. Methods: 68 cases of senile diabetes mellitus were randomly divided into control group with 34 cases ...Objective: to investigate the clinical effects of glargine and acarbose tablet in the treatment of senile diabetes. Methods: 68 cases of senile diabetes mellitus were randomly divided into control group with 34 cases and observation group with 34 cases. During clinical treatment, the cases in the control group were treated only with acarbose tablets, while the observation group was treated with insulin glargine. The relevant treatment effects of the two groups were comprehensively analyzed. Results: through drug treatment, in the comparison of treatment effective results, the effect of comprehensive treatment in the observation group was better. In addition, compared with the control group, the related data indexes of the observation group were more stable and obvious than those of the control group. The relative data index of P did not exceed 0.05. Conclusion: during the clinical treatment, the combination therapy of glargine and acarbose tablet can effectively improve the cure rate of the elderly patients. The blood glucose level should be significantly optimized and should be popularized in clinic.展开更多
Background:Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia.We compared the effects of acarbose and sitagliptin add ...Background:Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia.We compared the effects of acarbose and sitagliptin add on to metformin on time in range(TIR)and glycemic variability(GV)in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring(CGM).Methods:This study was a randomized,open-label,active-controlled,parallel-group trial conducted at 15 centers in China from January 2020 to August 2022.We recruited patients with type 2 diabetes aged 18–65 years with body mass index(BMI)within 19–40 kg/m 2 and hemoglobin A1c(HbA1c)between 6.5%and 9.0%.Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days.After the first 14-day treatment period,patients wore CGM and entered another 14-day treatment period.The primary outcome was the level of TIR after treatment between groups.We also performed time series decomposition,dimensionality reduction,and clustering using the CGM data.Results:A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin.There was no statistically significant difference in TIR between the two groups.Time below range(TBR)and coefficient of variation(CV)levels in acarbose users were significantly lower than those in sitagliptin users.Median(25th percentile,75th percentile)of TBR below target level<3.9 mmol/L(TBR 3.9):Acarbose:0.45%(0,2.13%)vs.Sitagliptin:0.78%(0,3.12%),P=0.042;Median(25th percentile,75th percentile)of TBR below target level<3.0 mmol/L(TBR 3.0):Acarbose:0(0,0.22%)vs.Sitagliptin:0(0,0.63%),P=0.033;CV:Acarbose:22.44±5.08%vs.Sitagliptin:23.96±5.19%,P<0.001.By using time series analysis and clustering,we distinguished three groups of patients with representative metabolism characteristics,especially in GV(group with small wave,moderate wave and big wave).No significant difference was found in the complexity of glucose time series index(CGI)between acarbose users and sitagliptin users.By using time series analysis and clustering,we distinguished three groups of patients with representative metabolism characteristics,especially in GV.Conclusions:Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia.Time series analysis of CGM data may predict GV and the risk of hypoglycemia.Trial Registration:Chinese Clinical Trial Registry:ChiCTR2000039424.展开更多
Background Glycemic variability, an HbAlc-independent risk factor, has more deleterious effects than sustained hyperglycemia in the development of diabetic complications. This study analyzed the characteristics of gly...Background Glycemic variability, an HbAlc-independent risk factor, has more deleterious effects than sustained hyperglycemia in the development of diabetic complications. This study analyzed the characteristics of glycemic variability in type 2 diabetes mellitus （T2DM） with HbAlc 〈6.5% in duration of twice daily premixed insulin treatment and the effect of further treatment with acarbose. Methods Eighty-six T2DM patients who used premixed insulin analogue （insulin aspart 30） twice daily and had HbAlc 〈6.5% and 20 controlled subjects with normal glucose regulation （NGR） were monitored using the continuous glucose monitoring （CGM） system. The mean amplitude of glycemic excursions （MAGE）, mean of daily differences （MODD） were used for assessing intra-day, inter-day glycemic variability. Hypoglycemia was defined as glucose level 〈3.9 mmol/L for at least 15 minutes in CGM. According to reference values of MAGE, T2DM patients were classified into two groups： Iow-MAGE group with MAGE 〈3.4 mmol/L （L-MAGE） and high-MAGE group with MAGE 〉3.4 mmol/L （H-MAGE）. H-MAGE group received further treatment with acarbose for 2 weeks and was monitored a second time with CGM system. Results After first CGM, L-MAGE group had 41 cases, and H-MAGE group had 45 cases. The MAGE and MODD of T2DM group were all higher than those of subjects with NGR （P 〈0.01）. Twenty-four percent （n=11） in H-MAGE group had a total of 13 hypoglycemic events, 10 of the 13 events occurred at night, meanwhile 5% （n=-2） in L-MAGE group had a total of 2 hypoglycemic events, which also occurred at night （hypoglycemic events： 24% vs. 5%, X2=6.40, P 〈0.01）. MAGE value was correlated with hypoglycemia value and 2-hour postprandial plasma glucose value （r=-0.32 and 0.26, respectively, P 〈0.05）. After further acarbose therapy and secondly CGM, MAGE and MODD values in H-MAGE group were all significantly decreased （40%, P 〈0.01, and 15%, P 〈0.05, respectively）, but remained higher than in the subjects with NGR （P 〈0.05）; 2% （n=-l） had a total of 1 hypoglycemic event, incidence significantly decreased （2% vs. 24%, X2=9.61, P 〈0.01）. Conclusions CGM system can detect the glycemic variability and asymptomatic hypoglycemic events of T2DM with well-controlled HbAlc in duration of insulin treatment. Combination therapy of premixed insulin twice daily with acarbose can flat glycemic variability and decrease hypoglycemic events.展开更多
Background Postprandial hypotension （PPH） occurs frequently in elderly people and may lead to syncope, falls, dizziness, weakness, angina pectoris, and stroke. Some studies suggest that the magnitude of the postpran...Background Postprandial hypotension （PPH） occurs frequently in elderly people and may lead to syncope, falls, dizziness, weakness, angina pectoris, and stroke. Some studies suggest that the magnitude of the postprandial fall in blood pressure （BP） is influenced by the rate at which glucose enters the small intestine. We hypothesized that acarbose （α-glucosidase inhibitor）, a hypoglycemic agent that decreases the rate of glucose absorption in the small intestine, would attenuate PPH in the elderly, and would be safe in the treatment. Methods Forty-three elderly in-patients with PPH were recruited. All of them were in relatively stable conditions. They had semi-liquid standard meals without and with acarbose for the two following days： screening day and intervention day. Blood pressure and heart rate （HR） were recorded at baseline and every 15 minutes for 120 minutes using a non-invasive ambulatory blood pressure monitoring system during the study, and ejection fraction （EF） and fractional shortening （FS） were measured by two dimensional echocardiography. Results Compared with the screening day, the falls in systolic, diastolic and mean arterial blood pressure （SBP, DBP, MAP） （all P 〈0.05） were significantly attenuated after taking acarbose during breakfast, so were MAP （P 〈0.05） during lunch, DBP （P 〈0.05） and MAP （P 〈0.05） during supper. The change of HR was not statistically significant after taking acarbose in three meals. EF and FS were positively correlated with the relief rate. The effective power was 63%, and the incidence of adverse drug reaction （ADR） was 9%. Conclusion Acarbose is effective and safe in the treatment of elderly patients with PPH.展开更多
Theα-glucosidase inhibitor acarbose is commercially produced by Actinoplanes sp.and used as a potent drug in the treatment of type-2 diabetes.In order to improve the yield of acarbose,an efficient genetic manipulatio...Theα-glucosidase inhibitor acarbose is commercially produced by Actinoplanes sp.and used as a potent drug in the treatment of type-2 diabetes.In order to improve the yield of acarbose,an efficient genetic manipulation system for Actinoplanes sp.was established.The conjugation system between E.coli carryingØC31-derived integrative plasmids and the mycelia of Actinoplanes sp.SE50/110 was optimized by adjusting the parameters of incubation time of mixed culture(mycelia and E.coli),quantity of recipient cells,donor-to-recipient ratio and the concentration of MgCl2,which resulted in a high conjugation efficiency of 29.4%.Using this integrative system,a cloned acarbose biosynthetic gene cluster was introduced into SE50/110,resulting in a 35%increase of acarbose titer from 2.35 to 3.18 g/L.Alternatively,a pIJ101-derived replicating plasmid combined with the counter-selection system CodA(sm)was constructed for gene inactivation,which has a conjugation frequency as high as 0.52%.Meanwhile,almost all 5-flucytosine-resistant colonies were sensitive to apramycin,among which 75%harbored the successful deletion of targeted genes.Using this replicating vector,the maltooligosyltrehalose synthase gene treY responsible for the accumulation of component C was inactivated,and component C was eliminated as detected by LC-MS.Based on an efficient genetic manipulation system,improved acarbose production and the elimination of component C in our work paved a way for future rational engineering of the acarbose-producing strains.展开更多
Theα-glucosidase inhibitor acarbose is produced in large-scale by strains derived from Actinoplanes sp.SE50 and used widely for the treatment of type-2 diabetes.Compared with the wild-type SE50,a high-yield derivativ...Theα-glucosidase inhibitor acarbose is produced in large-scale by strains derived from Actinoplanes sp.SE50 and used widely for the treatment of type-2 diabetes.Compared with the wild-type SE50,a high-yield derivative Actinoplanes sp.SE50/110 shows 2-fold and 3–7-fold improvement of acarbose yield and acb cluster transcription,respectively.The genome of SE50 was fully sequenced and compared with that of SE50/110,and 11 SNVs and 4 InDels,affecting 8 CDSs,were identified in SE50/110.The 8 CDSs were individually inactivated in SE50.Deletions of ACWT_4325(encoding alcohol dehydrogenase)resulted in increases of acarbose yield by 25%from 1.87 to 2.34 g/L,acetyl-CoA concentration by 52.7%,and PEP concentration by 22.7%.Meanwhile,deletion of ACWT_7629(encoding elongation factor G)caused improvements of acarbose yield by 36%from 1.87 to 2.54 g/L,transcription of acb cluster,and ppGpp concentration to 2.2 folds.Combined deletions of ACWT_4325 and ACWT_7629 resulted in further improvement of acarbose to 2.83 g/L(i.e.76%of SE50/110),suggesting that the metabolic perturbation and improved transcription of acb cluster caused by these two mutations contribute substantially to the acarbose overproduction.Enforced application of similar strategies was performed to manipulate SE50/110,resulting in a further increase of acarbose titer from 3.73 to 4.21 g/L.Therefore,the comparative genomics approach combined with functional verification not only revealed the acarbose overproduction mechanisms,but also guided further engineering of its high-yield producers.展开更多
Objective To evaluate the effects of Acarbose on incretin level(glucagon-like peptide 1(GLP-1)and gastric inhibitory polypeptide(GIP)of type 2 diabetes mellitus(T2DM)patients after different kinds of glucose load.Meth...Objective To evaluate the effects of Acarbose on incretin level(glucagon-like peptide 1(GLP-1)and gastric inhibitory polypeptide(GIP)of type 2 diabetes mellitus(T2DM)patients after different kinds of glucose load.Methods A total of 32 newly diagnosed T2DM patients were enrolled in this study and randomly divided into展开更多
Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus(T2DM).Various acarbose analogs have been identified while exploring compounds with improved pharmacological ...Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus(T2DM).Various acarbose analogs have been identified while exploring compounds with improved pharmacological properties.In this study,we found that AcbE from Actinoplanes sp.SE50/110 catalyzes the production of acarbose analogs that exhibit significantly improved inhibitory activity towardsα-amylase than acarbose.Recombinant AcbE mainly catalyzed the formation of two new compounds,namely acarstatins A and B,using acarbose as substrate.Using high-resolution mass spectrometry,nuclear magnetic resonance,and glycosidase hydrolysis,we elucidated their chemical structures as O-α-d-maltosyl-(1→4)-acarbose and O-α-d-maltotriosyl-(1→4)-acarbose,respectively.Acarstatins A and B exhibited 1584-and 1478-fold greater inhibitory activity towards human salivaryα-amylase than acarbose.Furthermore,both acarstatins A and B exhibited complete resistance to microbiome-derived acarbose kinase 1-mediated phosphorylation and partial resistance to acarbose-preferred glucosidase-mediated hydrolysis.Therefore,acarstatins A and B have great potential as candidate therapeutic agents for T2DM.展开更多
The Aearbose Cardiovascular Evaluation(ACE)trial assessed whether acarbose could reduce the incidence of cardiovascular event(CVE)s in Chinese patients suffering from impaired glucose tolerance(IGT)and coronary heart ...The Aearbose Cardiovascular Evaluation(ACE)trial assessed whether acarbose could reduce the incidence of cardiovascular event(CVE)s in Chinese patients suffering from impaired glucose tolerance(IGT)and coronary heart disease.ACE differs from a previous study on IGT people,the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus(STOP-NIDDM)trial in terms of sample size,number of CVE,mean age,aearbose dose,and population.ACE supported STOP-NIDDM's results by showing that acarbose prevents the progression of prediabetes to diabetes in IGT people,and extended the effect to people with coronary heart disease.However it did not reduce CVE incidence,probably due to the low dose used(50 mg tid).Overall,ACE is well-designed and highpowered enough to confirm that acarbose can prevent progression of prediabetes to diabetes,but is not able to reduce CVE incidence.However,in light of the fast growing prediabetic Chinese population,usage of acarbose is warranted to avert an explosion of diabetes.展开更多
基金Supported by the National Basic Research Program of China(2011CB710800)National Special Program for Key Science and Technology of China(2008ZX09204-004)
文摘Acarbose, a potent α-glucosidase inhibitor, is widely used as an oral anti-diabetic drug for the treatment of the type 2, non-insulin-dependent diabetes. In this work, a gel type strong acid cation exchange resin 001×4 was applied to isolate acarbose from fermentation broth. It was demonstrated that cation exchanger 001×4 displayed a large adsorption capacity and quick exchange rate for acarbose. The static adsorption equilibrium data were well fitted to the Langmuir equation. Column adsorption experiments demonstrated that high dynamic adsorption capacity was reached at bed height of 104.4 mm, feed flow rate of 1.0 ml·min 1and acarbose concentration of 4.0 mg·ml 1.Under the optimized conditions, the column chromatography packed with cation exchanger 001×4 recovered 74.3%(by mass) of acarbose from Actinoplanes utahensis ZJB-08196 fermentation broth with purity of 80.1%(by mass),demonstrating great potential in the practical applications in acarbose separation.
基金Supported by Grant for Promotion of Science from Tottori Bioscience Foundation(1997-1998)Japan and Japanese Government(Ministry of Education,Science and Culture of Japan,MONBUSHO)scholarship No.933241(1994-1999)Japan in part.Dr.Luo was supported by the scholarships.
文摘AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS: The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS: The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P 【0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION: There are augmented effects of acarbose and GA,which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination.
文摘Acarbose is an agent that has been used to treat type 2 diabetes for about 30 years;it prevents postprandial hyperglycemia by inhibiting carbohydrate digestion in the small intestine.Since incretin-based treatments have been preferred over the last 10 to 15 years,the use of acarbose is not as common in treating type 2 diabetes as before.Some studies have shown that acarbose also produces a weight-loss effect by increasing glucagon-like peptide 1(GLP-1).The positive effect of acarbose on GLP-1,and increasing evidence that it provides cardiovascular protection,suggests that acarbose may again be considered among the first-choice antidiabetic agents,as it was in the 1990s.
基金This study is registered at Chinese Clinical Trial Registry Center.The registration number is ChiCTRTRC-08000231.
文摘BACKGROUND The waist-to-height ratio(WHtR)is a promising anthropometric measure used to evaluate cardiovascular risk in diabetes and metabolic syndrome patients.The metformin and acarbose in Chinese as the initial hypoglycaemic treatment trial demonstrated that acarbose and metformin reduced the WHtR after 24 wk of treatment.AIM To investigate the factors associated with a decrease in the WHtR in newly diagnosed Chinese type 2 diabetes patients receiving acarbose or metformin monotherapy.METHODS At 24 wk,343 patients in the acarbose treatment and 333 patients in the metformin treatment were included in this analysis.On the basis of the reduction in the WHtR,these participants were divided into the following two groups:LowΔWHtR group and highΔWHtR group.Metabolic and related parameters associated with a highΔWHtR were investigated using univariate and multivariate logistic regression analyses.RESULTS A significant decrease in the WHtR was observed in both treatment groups(acarbose:-0.015,95%confidence interval[CI]:-0.018 to-0.012,P<0.001;metformin:-0.013,95%CI:-0.016 to-0.010,P<0.001).In both the acarbose and metformin groups,the WHtR of the women was more likely to be reduced than that of the men.In the acarbose group,a lower baseline area under the curve of glucagon-like peptide 1(AUCGLP-1)was associated with a highΔWHtR(odds ratio[OR]=0.796,P<0.001),while a higher baseline AUCGLP-1 was associated with a highΔWHtR in the patients treated with metformin(OR=1.133,P=0.025).Regarding the changes from baseline,an increase in AUCGLP-1 was associated with a highΔWHtR in the acarbose(OR=1.121,P=0.016)but not metformin group.A higher reduction in high-density lipoprotein cholesterol/non-highdensity lipoprotein cholesterol was also associated with a highΔWHtR in the acarbose arm(OR=20.735,P=0.001).In the metformin arm,a higher reduction in fasting plasma glucose(OR=0.843,P=0.039)and total cholesterol was associated with a highΔWHtR(OR=0.743,P=0.013).CONCLUSION A lower glucagon-like peptide 1 level and higher increase in glucagon-like peptide 1 are associated with a high reduction in the WHtR in newly diagnosed Chinese diabetes patients receiving treatment with acarbose.
文摘Objective:To discuss the effect of the combined therapy of levemir and acarbose on T cell subsets and function of isletβ cells in elder patients with early-onset type 2 Diabetes Mellitus. Methods:According to the number parity of entry sequence, 100 cases of elder patients with early-onset type 2 Diabetes Mellitus are divided into the control group and the observation group of 50 cases. The control group was treated with novolin and acarbose, the observation group was given subcutaneous injection of levemir and acarbose treatment. Compare the T cell subsets and function of isletβ cells in two group of patients before the treatment (T0), treatment for 4 weeks (T1) ,treatment for 8 weeks (T2).Results:(1) The levels of T0, T1, T2CD3+, CD4+, CD4+/CD8+ were increased in both groups, and CD8+ decreased. Among them, the levels of T1, T2CD3+, CD4+, CD4+/CD8+ of the observation group were obviously higher than the control group, the level of CD8+ was lowly than the control group, the difference was statistically significant;(2) In the stage of T0, T1, T2, the levels of FPG, HbA1c, HOMA-IR were showed a downward trend, the levels of FIns, HOMA-B were increased. In these two groups, the levels of T1, T2FPG, HbA1c, HOMA-IR of the observation group were lower than the control group, and the levels of FIns, HOMA-B were higher than the control group, the difference was statistically significant;(3) In the control group occurred 3 cases of hypoglycemia, and the incidence of adverse reactions was 6%. However, in the observation group no occurred adverse reactions, the difference was statistically significant.Conclusions:The combined therapy of levemir and acarbose in elder patients with early-onset type 2 Diabetes Mellitus, It helps to improve immune function, protect the isletβ-cell function.
文摘Objectives: To investigate the effects of insulin resistance on serum androgen level and ovulation of women with polycystic ovary syndrome (PCOS) and observe clinic role of acarbose in the treatment of hyperinsulinemia, postprandial hyperglycemia and anovulation. Methods: 14 women accompanied by postprandial hyperglycemia with PCOS were administrated by acarbose for 12 weeks.14 age-matched individuals who had similar body mass index and normal menstruation were served as controls. Results: Serum T levels declined significantly from 4.09±1.04 nmol/L to 1.71±0.54 nmol/L (P<0.001), after acarbose treatment for 12 weeks. 12 out of 14 cases restored ovulation and menstrual cycles after acarbose treatment, among which 4 got pregnant. Conclusion: Acarbose may play a role on reducing postprandial hyperglycemia and HbAic levels, increase ISI and FSG/FI, indirectly reduce serum androgen levels through reducing plasma insulin level and recover ovarian ovulation in PCOS women with postprandial hyperglycemia.
文摘Acarbose is used to control postpran-dial blood glucose in patients with type 2 diabetes and impaired glucose tolerance,since it improves insulin resistance and reduces blood lipids and cardiovascular complications.However,in recent years,many studies have found that acarbose can mediate and regulate a variety of neurotransmitter-related diseases,although the mechanisms are not clear.Therefore,this paper analyzes the clinical effect of acarbose and its mediating effect on neurotransmitters of mental disorders through insulin,braingut axis,and calorie restriction,to provide a reference for the new clinical applications of acarbose.
文摘Objective: to analyze the application value of metformin combined with acarbose in the treatment of type 2 diabetes. Methods: we selected 100 recently admitted patients with type 2 diabetes, the control group adopted the existing treatment method centered on metformin, and the experimental group adopted the acarbose treatment based on metformin. The relationship between the time required for glycosylated hemoglobin to reach the standard and the effective cure rate between the two patient groups. Results: after the observation, it can be found that the experimental group adopts the combined treatment, the blood sugar and insulin resistance are more effective when reaching the standard, and the total effective rate of the treatment is higher than that of the control group. Conclusion: it can be concluded that the combination therapy of metformin and acarbose has a good effect on the treatment of type 2 diabetes. It has an obvious effect on the clinical treatment of diabetes and the reduction of blood sugar, and is worthy of promotion.
文摘Objective: to investigate the clinical effects of glargine and acarbose tablet in the treatment of senile diabetes. Methods: 68 cases of senile diabetes mellitus were randomly divided into control group with 34 cases and observation group with 34 cases. During clinical treatment, the cases in the control group were treated only with acarbose tablets, while the observation group was treated with insulin glargine. The relevant treatment effects of the two groups were comprehensively analyzed. Results: through drug treatment, in the comparison of treatment effective results, the effect of comprehensive treatment in the observation group was better. In addition, compared with the control group, the related data indexes of the observation group were more stable and obvious than those of the control group. The relative data index of P did not exceed 0.05. Conclusion: during the clinical treatment, the combination therapy of glargine and acarbose tablet can effectively improve the cure rate of the elderly patients. The blood glucose level should be significantly optimized and should be popularized in clinic.
文摘Background:Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia.We compared the effects of acarbose and sitagliptin add on to metformin on time in range(TIR)and glycemic variability(GV)in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring(CGM).Methods:This study was a randomized,open-label,active-controlled,parallel-group trial conducted at 15 centers in China from January 2020 to August 2022.We recruited patients with type 2 diabetes aged 18–65 years with body mass index(BMI)within 19–40 kg/m 2 and hemoglobin A1c(HbA1c)between 6.5%and 9.0%.Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days.After the first 14-day treatment period,patients wore CGM and entered another 14-day treatment period.The primary outcome was the level of TIR after treatment between groups.We also performed time series decomposition,dimensionality reduction,and clustering using the CGM data.Results:A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin.There was no statistically significant difference in TIR between the two groups.Time below range(TBR)and coefficient of variation(CV)levels in acarbose users were significantly lower than those in sitagliptin users.Median(25th percentile,75th percentile)of TBR below target level<3.9 mmol/L(TBR 3.9):Acarbose:0.45%(0,2.13%)vs.Sitagliptin:0.78%(0,3.12%),P=0.042;Median(25th percentile,75th percentile)of TBR below target level<3.0 mmol/L(TBR 3.0):Acarbose:0(0,0.22%)vs.Sitagliptin:0(0,0.63%),P=0.033;CV:Acarbose:22.44±5.08%vs.Sitagliptin:23.96±5.19%,P<0.001.By using time series analysis and clustering,we distinguished three groups of patients with representative metabolism characteristics,especially in GV(group with small wave,moderate wave and big wave).No significant difference was found in the complexity of glucose time series index(CGI)between acarbose users and sitagliptin users.By using time series analysis and clustering,we distinguished three groups of patients with representative metabolism characteristics,especially in GV.Conclusions:Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia.Time series analysis of CGM data may predict GV and the risk of hypoglycemia.Trial Registration:Chinese Clinical Trial Registry:ChiCTR2000039424.
文摘Background Glycemic variability, an HbAlc-independent risk factor, has more deleterious effects than sustained hyperglycemia in the development of diabetic complications. This study analyzed the characteristics of glycemic variability in type 2 diabetes mellitus （T2DM） with HbAlc 〈6.5% in duration of twice daily premixed insulin treatment and the effect of further treatment with acarbose. Methods Eighty-six T2DM patients who used premixed insulin analogue （insulin aspart 30） twice daily and had HbAlc 〈6.5% and 20 controlled subjects with normal glucose regulation （NGR） were monitored using the continuous glucose monitoring （CGM） system. The mean amplitude of glycemic excursions （MAGE）, mean of daily differences （MODD） were used for assessing intra-day, inter-day glycemic variability. Hypoglycemia was defined as glucose level 〈3.9 mmol/L for at least 15 minutes in CGM. According to reference values of MAGE, T2DM patients were classified into two groups： Iow-MAGE group with MAGE 〈3.4 mmol/L （L-MAGE） and high-MAGE group with MAGE 〉3.4 mmol/L （H-MAGE）. H-MAGE group received further treatment with acarbose for 2 weeks and was monitored a second time with CGM system. Results After first CGM, L-MAGE group had 41 cases, and H-MAGE group had 45 cases. The MAGE and MODD of T2DM group were all higher than those of subjects with NGR （P 〈0.01）. Twenty-four percent （n=11） in H-MAGE group had a total of 13 hypoglycemic events, 10 of the 13 events occurred at night, meanwhile 5% （n=-2） in L-MAGE group had a total of 2 hypoglycemic events, which also occurred at night （hypoglycemic events： 24% vs. 5%, X2=6.40, P 〈0.01）. MAGE value was correlated with hypoglycemia value and 2-hour postprandial plasma glucose value （r=-0.32 and 0.26, respectively, P 〈0.05）. After further acarbose therapy and secondly CGM, MAGE and MODD values in H-MAGE group were all significantly decreased （40%, P 〈0.01, and 15%, P 〈0.05, respectively）, but remained higher than in the subjects with NGR （P 〈0.05）; 2% （n=-l） had a total of 1 hypoglycemic event, incidence significantly decreased （2% vs. 24%, X2=9.61, P 〈0.01）. Conclusions CGM system can detect the glycemic variability and asymptomatic hypoglycemic events of T2DM with well-controlled HbAlc in duration of insulin treatment. Combination therapy of premixed insulin twice daily with acarbose can flat glycemic variability and decrease hypoglycemic events.
基金This work was supported by a grant from the National Natural Science Foundation of Hunan Province （No. 05JJ30158）.
文摘Background Postprandial hypotension （PPH） occurs frequently in elderly people and may lead to syncope, falls, dizziness, weakness, angina pectoris, and stroke. Some studies suggest that the magnitude of the postprandial fall in blood pressure （BP） is influenced by the rate at which glucose enters the small intestine. We hypothesized that acarbose （α-glucosidase inhibitor）, a hypoglycemic agent that decreases the rate of glucose absorption in the small intestine, would attenuate PPH in the elderly, and would be safe in the treatment. Methods Forty-three elderly in-patients with PPH were recruited. All of them were in relatively stable conditions. They had semi-liquid standard meals without and with acarbose for the two following days： screening day and intervention day. Blood pressure and heart rate （HR） were recorded at baseline and every 15 minutes for 120 minutes using a non-invasive ambulatory blood pressure monitoring system during the study, and ejection fraction （EF） and fractional shortening （FS） were measured by two dimensional echocardiography. Results Compared with the screening day, the falls in systolic, diastolic and mean arterial blood pressure （SBP, DBP, MAP） （all P 〈0.05） were significantly attenuated after taking acarbose during breakfast, so were MAP （P 〈0.05） during lunch, DBP （P 〈0.05） and MAP （P 〈0.05） during supper. The change of HR was not statistically significant after taking acarbose in three meals. EF and FS were positively correlated with the relief rate. The effective power was 63%, and the incidence of adverse drug reaction （ADR） was 9%. Conclusion Acarbose is effective and safe in the treatment of elderly patients with PPH.
基金We are grateful to Prof.Yuhui Sun from Wuhan university,China,and the late Prof.Keqian Yang from Institute of Microbiology,Chinese Academy of Sciences,for providing plasmids pWHU2653 and pDR-4-K^*,respectively.This work was supported by grants from the National Natural Science Foundation of China(No.31470157,21661140002)the Ministry of Science and Technology of China(No.2012AA02A706).
文摘Theα-glucosidase inhibitor acarbose is commercially produced by Actinoplanes sp.and used as a potent drug in the treatment of type-2 diabetes.In order to improve the yield of acarbose,an efficient genetic manipulation system for Actinoplanes sp.was established.The conjugation system between E.coli carryingØC31-derived integrative plasmids and the mycelia of Actinoplanes sp.SE50/110 was optimized by adjusting the parameters of incubation time of mixed culture(mycelia and E.coli),quantity of recipient cells,donor-to-recipient ratio and the concentration of MgCl2,which resulted in a high conjugation efficiency of 29.4%.Using this integrative system,a cloned acarbose biosynthetic gene cluster was introduced into SE50/110,resulting in a 35%increase of acarbose titer from 2.35 to 3.18 g/L.Alternatively,a pIJ101-derived replicating plasmid combined with the counter-selection system CodA(sm)was constructed for gene inactivation,which has a conjugation frequency as high as 0.52%.Meanwhile,almost all 5-flucytosine-resistant colonies were sensitive to apramycin,among which 75%harbored the successful deletion of targeted genes.Using this replicating vector,the maltooligosyltrehalose synthase gene treY responsible for the accumulation of component C was inactivated,and component C was eliminated as detected by LC-MS.Based on an efficient genetic manipulation system,improved acarbose production and the elimination of component C in our work paved a way for future rational engineering of the acarbose-producing strains.
基金the National Natural Science Foundation of China(No.31470157,21661140002,31830104,U1703236)the Shanghai Science and Technology Committee(No.17JC1403600)。
文摘Theα-glucosidase inhibitor acarbose is produced in large-scale by strains derived from Actinoplanes sp.SE50 and used widely for the treatment of type-2 diabetes.Compared with the wild-type SE50,a high-yield derivative Actinoplanes sp.SE50/110 shows 2-fold and 3–7-fold improvement of acarbose yield and acb cluster transcription,respectively.The genome of SE50 was fully sequenced and compared with that of SE50/110,and 11 SNVs and 4 InDels,affecting 8 CDSs,were identified in SE50/110.The 8 CDSs were individually inactivated in SE50.Deletions of ACWT_4325(encoding alcohol dehydrogenase)resulted in increases of acarbose yield by 25%from 1.87 to 2.34 g/L,acetyl-CoA concentration by 52.7%,and PEP concentration by 22.7%.Meanwhile,deletion of ACWT_7629(encoding elongation factor G)caused improvements of acarbose yield by 36%from 1.87 to 2.54 g/L,transcription of acb cluster,and ppGpp concentration to 2.2 folds.Combined deletions of ACWT_4325 and ACWT_7629 resulted in further improvement of acarbose to 2.83 g/L(i.e.76%of SE50/110),suggesting that the metabolic perturbation and improved transcription of acb cluster caused by these two mutations contribute substantially to the acarbose overproduction.Enforced application of similar strategies was performed to manipulate SE50/110,resulting in a further increase of acarbose titer from 3.73 to 4.21 g/L.Therefore,the comparative genomics approach combined with functional verification not only revealed the acarbose overproduction mechanisms,but also guided further engineering of its high-yield producers.
文摘Objective To evaluate the effects of Acarbose on incretin level(glucagon-like peptide 1(GLP-1)and gastric inhibitory polypeptide(GIP)of type 2 diabetes mellitus(T2DM)patients after different kinds of glucose load.Methods A total of 32 newly diagnosed T2DM patients were enrolled in this study and randomly divided into
基金This work was supported by the National Key Research and Development Program of China(grant No.2021YFC2100600)National Natural Science Foundation of China(grant No.31830104)Science and Technology Commission of Shanghai Municipality(grant Nos.19JC1413000 and 19430750600)to L.B.We thank the Core Facility and Technical Service Center for SLSB and the Instrumental Analysis Center in SJTU for data collection.
文摘Acarbose is a potent glycosidase inhibitor widely used in the clinical treatment of type 2 diabetes mellitus(T2DM).Various acarbose analogs have been identified while exploring compounds with improved pharmacological properties.In this study,we found that AcbE from Actinoplanes sp.SE50/110 catalyzes the production of acarbose analogs that exhibit significantly improved inhibitory activity towardsα-amylase than acarbose.Recombinant AcbE mainly catalyzed the formation of two new compounds,namely acarstatins A and B,using acarbose as substrate.Using high-resolution mass spectrometry,nuclear magnetic resonance,and glycosidase hydrolysis,we elucidated their chemical structures as O-α-d-maltosyl-(1→4)-acarbose and O-α-d-maltotriosyl-(1→4)-acarbose,respectively.Acarstatins A and B exhibited 1584-and 1478-fold greater inhibitory activity towards human salivaryα-amylase than acarbose.Furthermore,both acarstatins A and B exhibited complete resistance to microbiome-derived acarbose kinase 1-mediated phosphorylation and partial resistance to acarbose-preferred glucosidase-mediated hydrolysis.Therefore,acarstatins A and B have great potential as candidate therapeutic agents for T2DM.
文摘The Aearbose Cardiovascular Evaluation(ACE)trial assessed whether acarbose could reduce the incidence of cardiovascular event(CVE)s in Chinese patients suffering from impaired glucose tolerance(IGT)and coronary heart disease.ACE differs from a previous study on IGT people,the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus(STOP-NIDDM)trial in terms of sample size,number of CVE,mean age,aearbose dose,and population.ACE supported STOP-NIDDM's results by showing that acarbose prevents the progression of prediabetes to diabetes in IGT people,and extended the effect to people with coronary heart disease.However it did not reduce CVE incidence,probably due to the low dose used(50 mg tid).Overall,ACE is well-designed and highpowered enough to confirm that acarbose can prevent progression of prediabetes to diabetes,but is not able to reduce CVE incidence.However,in light of the fast growing prediabetic Chinese population,usage of acarbose is warranted to avert an explosion of diabetes.
