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The purpose of this study was to determine the effect of an alpha-glucosidase inhibitor (acarbose), combined with a low-carbohydrate diet on the treatment of naturally occurring diabetes mellitus in cats. Eighteen client-owned cats with naturally occurring diabetes mellitus were entered into the study. Dual-energy X-ray absorptiometry (DEXA) was performed prior to and 4 months after feeding the diet to determine total body composition, including lean body mass (LBM) and percent body fat. Each cat was fed a commercially available low-carbohydrate canned feline diet and received 12.5mg/cat acarbose orally every 12h with meals. All cats received subcutaneous insulin therapy except one cat in the study group that received glipizide (5mg BID PO). Monthly serum glucose and fructosamine concentrations were obtained, and were used to adjust insulin doses based on individual cat's requirements. Patients were later classified as responders (insulin was discontinued, n=11) and non-responders (continued to require insulin or glipizide, n=7). Responders were initially obese (>28% body fat) and non-responders had significantly less body fat than responders (<28% body fat). Serum fructosamine and glucose concentrations decreased significantly in both responder and non-responder groups over the course of 4 months of therapy. Better results were observed in responder cats, for which exogenous insulin therapy was discontinued, glycemic parameters improved, and body fat decreased. In non-responders, median insulin requirements decreased and glycemic parameters improved significantly, despite continued insulin dependence. The use of a low-carbohydrate diet with acarbose was an effective means of decreasing exogenous insulin dependence and improving glycemic control in a series of client-owned cats with naturally occurring diabetes mellitus.
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In NIDDM patients inadequately controlled on conventional oral agents, acarbose in moderate doses resulted in beneficial effects on glycemic control, especially postprandial glycemia, and mean body weight. Additional use of acarbose can be considered as a useful alternative in such patients if they are reluctant to accept insulin therapy.
Characterization of polyphenolic compounds in the stems of P. multiflorum was conducted using HPLC, high resolution LC-MS and LC-MSn. Proanthocyanidins in particular were isolated in 4.8% yield using solvent extraction followed by Sephadex LH-20 fractionation. HPLC analysis using a diol column revealed oligomers (from dimer to nonamer) as minor components, with (epi)catechin monomeric units predominating, and oligomers with higher degree of polymerization being dominant. Thiolysis treatment of the proanthocyanidins using mercaptoacetic acid produced thioether derivatives of (epi)catechin as the major product and a mean value of the degree of polymerization of 32.6 was estimated from the ratio of terminal and extension units of the (epi)catechin. The isolated proanthocyanidins were shown to strongly inhibit α-amylase with an acarbose equivalence (AE) value of 1,954.7 µmol AE/g and inhibit α-glucosidase with an AE value of 211.1 µmol AE/g.
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Ascorbic acid (1), a natural antioxidant, was modified by employing transglycosylation activity of Bacillus stearothermophilus maltogenic amylase with maltotriose and acarbose as donor molecules to enhance its oxidative stability. The transglycosylation reaction with maltotriose as donor created mono- and di-glycosyl transfer products with an alpha-(1,6)-glycosidic linkage. In addition, two acarviosine-glucosyl transfer products were generated when transglycosylation was performed with acarbose as a donor. All transfer products were observed by TLC and HPLC, and purified by Q-sepharose anion exchange and Biogel P-2 gel permeation chromatographies. LC/MS and (13)C NMR analyses revealed that the structures of the transfer products were 6-O-alpha-D-glucosyl- (2) and 6-O-alpha-D-maltosyl-ascorbic acids (3) in the reaction of maltotriose, and 6-O-alpha-acarviosine-D-glucosyl- (4) and 2-O-alpha-acarviosine-D-glucosyl ascorbic acids (5) in the reaction of acarbose. The stability of the transglycosylated ascorbic acid derivatives was greatly enhanced against oxidation by Cu(2+) ion and ascorbate oxidase. Among them, compound 3 proved to be the most stable against in vitro oxidation. The antioxidant effects of glycosyl-derivatives of ascorbic acid on the lipid oxidation in cooked chicken breast meat patties indicated that they had antioxidant activities similar to that of ascorbic acid. It is suggested that the transglycosylated ascorbic acids can possibly be applied as effective antioxidants with improved stability in food, cosmetic, and other applications.
The validity of the results of the STOP-NIDDM trial is seriously flawed. The clinical benefit of Acarbose and of the reduction of post-prandial glycaemia is unproven.
Type 2 diabetes mellitus is characterized by insulin deficiency but in particular by insulin resistance. Patients where it is not possible to achieve positive results within 4-12 weeks by optimalization of the lifestyle are candidates for treatment with oral antidiabetics. At present the following main groups of oral antidiabetics are discussed: insulin secretagogues (SU derivatives and methiglinide derivatives), biguanides (Metformin), alpha-glucosidase inhibitors (acarbose, miglitol) and insulin sensitizers (thiazolindiones). Traditional SU therapy improves the insulin plasma levels by releasing insulin from the pancreas. This implies further stress on the b-cells and the function of these cells declines reversibly. Biguanides, such as metformin, are effective substances reducing the blood sugar level, they are however associated with the problem of tolerability and are contraindicated in some diabetics. A new approach to the treatment of type 2 diabetes are thiasolinediones, insulin-sensitizing substances, the molecular basis of their action being via activation of PPAR gamma-nuclear receptors with subsequent change in expression of genes participating in carbohydrate and lipid metabolism.
We are studied 92 patients with diabetes type 2, treated with Acarbose alone or with insuline or oral anti-diabetics We are determined the values of HbA1c, total cholesterol, HDL, LDL, triglycerides and microalbuminuria, before and after or the treatment with acarbose.
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Acarbose, a competitive α-glucosidase inhibitor, is clinically and widely used in the treatment of type II diabetes mellitus. In order to improve the industrial acarbose productivity by Actinoplanes sp. A56, the classical fermentation conditions such as total sugar concentration in broths, pH value and dissolved oxygen (DO) level were systematically investigated in a 30000-l fermenter, respectively. It was observed that a high-concentration total sugar (75-80 g/l), 7.0-7.2 of pH value and 40-50% of DO concentration were favorable for acarbose production. As a result, the final acarbose yield was elevated to approximately 5000 mg/l at 168 h of fermentation.
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To assess the cost-effectiveness of metformin-based dual therapies associated with cardiovascular disease (CVD) risk in a Chinese population with type 2 diabetes.
Helicteres isora (Sterculiaceae) root juice has been used in the treatment of diabetes by several ethnic groups in different parts of India. A program was initiated to elucidate the scientific basis for the antidiabetic activity of H. isora. Ethanolic extract of H. isora root caused significant reduction in plasma glucose, triglyceride and insulin levels at 300 mg/kg dose after 9 days of administration to insulin resistant and diabetic C57BL/KsJdb/db mice. In normoglycemic and mildly hypertriglyceridemic Swiss albino mice, the extract also showed significant reduction in plasma triglyceride and insulin levels, without affecting plasma glucose level. An ethanolic extract showed activity distinctly different from glybenclamide and acarbose but similar to troglitazone in these models. In high fat fed hamster model, the extract showed significant reduction in plasma lipid levels. In order to identify the active pharmacophore, the ethanolic extract was further subjected to sequential partitioning with low, medium and high polarity solvents, which yielded a semipurified fraction having both euglycemic and lipid-lowering activity. Our study suggests that the extract of H. isora has insulin-sensitizing and hypolipidemic activity and has the potential for use in the treatment of type-2 diabetes.
Eight randomized controlled trials with 2628 participants were included. Acarbose decreased the occurrence of T2DM (number needed to treat [NNT], 6.7). Compared with the control (placebo and/or lifestyle intervention), the incidence of T2DM was significantly lower in the Eastern group (NNT, 5.9) than in the Western group (NNT, 11.1) (P < 0.0001, I(2) = 94.7%). At the end of follow-up, reversal of prediabetes to normal glucose tolerance was more likely in the Eastern group (NNT, 4.3) than in the Western group (NNT, 25) (P = 0.004, I(2) = 92%). Among those remaining prediabetic, there was no significant difference between the subtotal estimates for the subgroups (P = 0.17, I(2) = 46.5%). There was no positive correlation between preventive effect and dose, and no difference in studies with varying follow-up durations within and across either ethnic group.
Postprandial hyperglycemia (PPH) and intermittent hypoxia related to the sleep apnea syndrome are important predictors of cardiovascular disease. We investigated the effects of intermittent hypoxia on pathological changes in the left ventricular (LV) myocardium caused by PPH in lean mice and evaluated the influence of acarbose, an α-glucosidase inhibitor. Male C57BL/6J mice aged 8 weeks were exposed to intermittent hypoxia (8 h/day during the daytime) or kept under normoxia. PPH was induced by restriction of feeding to 1-h periods twice a day, with the restricted diet (RD) mice receiving either standard chow or chow containing 0.02% acarbose. Another group of mice were fed standard chow ad libitum (AL). Plasma glucose levels after food intake were significantly elevated in RD but not in AL mice, and glucose levels were suppressed by acarbose. Intermittent hypoxia exacerbated cardiomyocyte hypertrophy and interstitial fibrosis in the LV myocardium of RD mice. Superoxide production and expression of 4-hydroxy-2-nonenal in the LV myocardium with intermittent hypoxia were increased in RD mice, but not AL mice. In addition, expression of tumor necrosis factor α (TNF-α) mRNA was increased in hypoxic RD mice. Treatment with acarbose inhibited oxidative stress and TNF-α mRNA expression and preserved the histological architecture of the LV myocardium.
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Drug repositioning can reduce the time, costs and risks of drug development by identifying new therapeutic effects for known drugs. It is challenging to reposition drugs as pharmacological data is large and complex. Subnetwork identification has already been used to simplify the visualization and interpretation of biological data, but it has not been applied to drug repositioning so far. In this paper, we fill this gap by proposing a new Physarum-inspired Prize-Collecting Steiner Tree algorithm to identify subnetworks for drug repositioning.
A series of hesperidin derivatives were prepared and identified by IR, (1)H NMR, and MS spectra. These compounds were evaluated in vitro and in vivo based on α-glucosidase inhibition, glucose consumption of HepG2 cells, and blood glucose level in streptozotocin-induced diabetic mice. The results revealed that all the compounds exhibited anti-hyperglycemic activities. The inhibition at 10(-3) M of compounds 3 and 7a on α-glucosidase were 55.02% and 53.34%, respectively, as compared to 54.80% by acarbose. Treated by compound 3 and the reference drug metformin, glucose consumption of HepG2 cell were 1.78 and 2.11 mM, respectively. After the streptozotocin-induced diabetic mice were oral administrated with compound 3 at 100 mg kg(-1) d(-1) for 10 days, the blood glucose level of 3 treated mice (13.23 mM, P<0.05) showed significant difference when compared to model control (23.03 mM). Thus, compound 3 exhibited promising anti-hyperglycemic activity.
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Acarbose, a pseudo-oligosaccharide, is widely used clinically in therapies for non-insulin-dependent diabetes. In the present study, S-adenosylmethionine (SAM) was added to selected media in order to investigate its effect on acarbose fermentation by Actinoplanes utahensis ZJB- 08196. Acarbose titer was seen to increase markedly when concentrations of SAM were added over a period of time. The effects of glucose and maltose on the production of acarbose were investigated in both batch and fed-batch fermentation. Optimal acarbose production was observed at relatively low glucose levels and high maltose levels. Based on these results, a further fed-batch experiment was designed so as to enhance the production of acarbose. Fed-batch fermentation was carried out at an initial glucose level of 10 g/l and an initial maltose level of 60 g/l. Then, 12 h post inoculation, 100 micromol/l SAM was added. In addition, 8 g/l of glucose was added every 24 h, and 20 g/l of maltose was added at 96 h. By way of this novel feeding strategy, the maximum titer of acarbose achieved was 6,113 mg/l at 192 h. To our knowledge, the production level of acarbose achieved in this study is the highest ever reported.
To investigate exenatide, a GLP-1 analogue, compared with acarbose, for intra-abdominal fat reduction in patients with obesity and type-2 diabetes.
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Median HbA1c was 66 ± 1 mmol/mol (8.2 ± 0.07%) in the metformin group at baseline, and 66 ± 1 mmol/mol (8.2 ± 0.07%) in the acarbose group. After 24 weeks of monotherapy, 79.8% of participants in the metformin group achieved glycaemic targets compared with 78.7% of those in the acarbose group. Multivariate regression analysis showed that BMI and fasting blood glucose were significant independent predictors for the maintenance of good glycaemic control in the metformin group, whereas phase I insulin secretion (Insulin/Glucose at 30 min, I30/G30) and duration of diabetes were associated with good glycaemic control in the acarbose group.
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In patients with IGT, doxazosin given in combination with acarbose seemed to improve glycaemic and lipid control compared with placebo, with the benefits observed appearing to extend beyond those expected from improvements in blood pressure. Patients in this study also benefited from acarbose therapy, which restored all patients from IGT to normal glucose tolerance status.
Gestational diabetes is considered as a carbohydrate intolerance, first diagnosed during pregnancy. A previous stage of carbohydrate impairement may precede its abnormality; therefore it may be convenient to establish some management in order to avoid the gestational diabetes. Six pregnant women who had moderate elevated level of blood glucose at fasting and postprandial were treated with acarbose, alpha-glucosidase inhibitor agent, given three times a day before meals. In all patients fasting and postprandial glucose levels were normalized; pregnancies went uneventful and the newborns were considered normal. Acarbose was associated with intestinal discomfort which persisted during the whole pregnancy.
To compare the health and economic outcomes of using acarbose, an intensive lifestyle modification programme, metformin or no intervention to prevent progression to diabetes in Canadian individuals with impaired glucose tolerance (IGT).
Nineteen plants from Fabaceae family, which were used in Thai traditional medicine for treatment of diabetes, were determined of α-glucosidase inhibitory activity via enzymatic reaction. In this reaction, α-glucosidase was used as enzyme, which, reacted with the substrate, p-nitrophenol-D-glucopyranoside (pNPG). After that the product, p-nitro phenol (pNP) will be occurred and observed the yellow colour at 405 nm. In this study, acarbose was used as positive standard which, inhibited this enzyme with IC₅₀ as 331 ± 4.73 μg/ml. Caesalpinia pulcherrima leaves showed the highest activity with IC₅₀ as 436.97 ± 9.44 μg/ml. Furthermore, Bauhinia malabarica leaves presented moderately activity with IC₅₀ as 745.08 ± 11.15 μg/ml. However, the other plants showed mild to none activity of α-glucosidase inhibition. Accordingly, this study can support anti-diabetes of these plants in traditional medicine and it will be the database of the biological activity of Fabaceae plant.