α-Glucosidase (α-D-Glucosidase) is a carbohydrate hydrolase that catalyzes the release of α-glucose from the non-reducing end of the substrate. Alpha-Glucosidase promotes glucose absorption in the small intestine. Inhibition of α-Glucosidase is an effective management approach for non-insulin-dependent diabetes mellitus (NIDDM).

Physicochemical Properties

Molecular Weight	0
CAS #	9001-42-7
Appearance	White to off-white solid powder
Synonyms	α-D-Glucosidase
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Carbohydrate hydrolyzing enzyme
ln Vitro	α-Glucosidase (α-d-glucoside glucohydrolase) is an exo-type carbohydrase distributed widely in microorganisms, plants, and animal tissues, which catalyzes the liberation of α-glucose from the non reducing end of the substrate. Inhibiting this enzyme slows the elevation of blood sugar following a carbohydrate meal. It is a membrane bound enzyme present in the epithelium of the small intestine, which works to facilitate the absorption of glucose by the small intestine by catalyzing the hydrolytic cleavage of oligosaccharides into absorbable [Figure 1] monosaccharides.[1] By the inhibition of α-glucosidase in the intestine, the rate of hydrolytic cleavage of oligosaccharide is decreased and the process of carbohydrate digestion spreads to the lower part of small intestine. This spreading of digestion process delays the overall absorption rate of glucose into the blood. This has proved to be one of the best strategies to decrease the postprandial rise in blood glucose and in turn help avoiding the onset of late diabetic complications. [1] There are reports of the presence of α-glucosidase inhibitors, such as acarbose andvoglibose, in microorganisms, and nojirimycin and 1-deoxynojirimycin in plants, as well as the effects of α-glucosidase inhibitor in wheat kernels on blood glucose levels after food uptake. [1] α-Glucosidase inhibitory potency of plant extracts and isolated compounds from different origins are discussed in Table 1. [1]
ln Vivo	α-Glucosidase is an enzyme that is membrane-bound and found in the epithelial cells of the small intestine. It facilitates the hydrolytic breakdown of oligosaccharides into forms that may be absorbed by the small intestine. After carbohydrate meals, the rise in blood glucose is slowed down by inhibiting α-glucosidase [1].
Animal Protocol	Forty-one studies were included in the review (30 acarbose, 7 miglitol, 1 voglibose, and 3 combined), and heterogeneity was limited. We found no evidence for an effect on mortality or morbidity. Compared with placebo, AGIs had a beneficial effect on GHb (acarbose -0.77%; miglitol -0.68%), fasting and postload blood glucose and postload insulin. With acarbose dosages higher than 50 mg t.i.d., the effect on GHb was the same, but the occurrence of side effects increased. Acarbose decreased the BMI by 0.17 kg/m2 (95% CI 0.08-0.26). None of the AGIs had an effect on plasma lipids. Compared with sulfonylurea, AGIs seemed inferior with respect to glycemic control, but they reduced fasting and postload insulin levels. For comparisons with other agents, little data were available. [2] Glycemic control [2] Compared with placebo, acarbose decreased GHb by 0.77% (95% CI 0.64–0.90) (online appendix A [available at http://care.diabetesjournals.org]) and miglitol by 0.68% (95% CI 0.44–0.93), respectively. For voglibose, only one study was available, which yielded a difference of 0.47% in favor of voglibose (95% CI 0.31–0.63). With respect to GHb, we found no evidence for a dose dependency for acarbose in the range from 50 to 300 mg t.i.d.. The subgroup analyses for acarbose 50, 100, 200, and 300 mg t.i.d. showed a decrease in GHb of 0.90, 0.76, 0.77, and 0.78%, respectively (online appendix A). In contrast, for miglitol, such a dose dependency seemed to be present; miglitol 25, 50, 100, and 200 mg t.i.d. decreased GHb by 0.46, 0.58, 0.79, and 1.26%, respectively. However, the results from this meta-analysis are based on seven comparisons, of which four were derived from one (multiarm) trial. [2] In the subgroup analysis and meta-regression analyses, we found a tendency toward a larger effect on GHb of acarbose at higher baseline levels for GHb. The subgroup analyses for studies with baseline GHb <7%, 7–9%, and >9% yielded a decrease in GHb of 0.56% (95% CI 0.36–0.76), 0.78% (95% CI 0.63–0.93), and 0.93% (95% CI 0.53–1.33), respectively. In the meta-regression analysis with the effect on GHb as dependent and baseline GHb as an independent variable, we found a regression coefficient of −0.12 (95% CI −0.26 to 0.03), indicating an extra 0.12% GHb decrease for every 1% higher baseline GHb. [2] The subgroup analysis for study duration indicated that long-term studies (more than 24 weeks) showed less effect on GHb. The decrease in GHb for studies with a duration of less than 24 weeks, equal to 24 weeks, and more than 24 weeks was 0.77% (95% CI 0.61–0.93), 0.82% (95% CI 0.63–1.01), and 0.53% (95% CI 0.20–0.87), respectively. This was mostly due to the data from the UKPDS (duration 156 weeks), in which a decrease of only 0.19% on GHb was found (95% CI −0.29–0.67). [2] In the subgroup and meta-regression analyses, we also found that the application of a fixed dosage scheme and the absence of a step-up dosage scheme increased the effect on glycemic control but also increased the occurrence of side effects (data not shown). [2] For acarbose, fasting blood glucose decreased by 1.09 mmol/l (28 comparisons; 95% CI 0.83–1.36), for miglitol by 0.52 mmol/l (2 comparisons; 95% CI 0.16–0.88), and for voglibose by 0.60 mmol/l (1 comparison; 95% CI 0.23–0.97). One-hour postload glucose decreased by 2.32 mmol/l (acarbose; 22 comparisons; 95% CI 1.92–2.73), 2.70 mmol/l (miglitol; 2 comparisons; 95% CI −0.14 to 5.54), and 2.40 mmol/l (voglibose; 1 comparison; 95% CI 1.83–2.97). In contrast to the outcome for GHb, acarbose showed a dose-dependent decrease of postload glucose. Acarbose 50, 100, 200, and 300 mg t.i.d. reduced postload glucose by 1.63, 2.26, 2.78, and 3.62 mmol/l, respectively (online appendix B). [2] Data from studies that compared AGI with other blood glucose lowering interventions were scarce. Pooling of results was only possible for the comparison of acarbose with sulfonylurea. The overall comparison of acarbose with sulfonylurea yielded a nonsignificant advantage for sulfonylurea with respect to overall GHb of 0.38% (data not shown; online appendix C). However, seven of the studies in the meta-analyses used unequal comparators, because they compared a fixed dose of acarbose with individually adjusted dosages of sulfonylurea or a usual dose of acarbose with a very low dose of glibenclamide. The results for the subgroup “acarbose 100 mg versus glibenclamide 3.5 mg” were not consistent with the other comparisons. This discrepancy remained unexplained. Leaving this subgroup out of the meta-analysis yielded an overall effect of 0.63% (95% CI 0.26–1.00) in favor of sulfonylurea. In the same comparison, outcomes for the meta-analyses for fasting and 1-h postload blood glucose were 0.69 mmol/l in favor of sulfonylurea (95% CI 0.16–1.23) and 0.10 mmol/l in favor of acarbose (95% CI −0.43 to 0.22). [2]
References	[1]. α-glucosidase inhibitors from plants: A natural approach to treat diabetes. Pharmacogn Rev. 2011 Jan;5(9):19-29. [2]. Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care. 2005 Jan;28(1):154-63.
Additional Infomation	Diabetes is a common metabolic disease characterized by abnormally high plasma glucose levels, leading to major complications, such as diabetic neuropathy, retinopathy, and cardiovascular diseases. One of the effective managements of diabetes mellitus, in particular, non-insulin-dependent diabetes mellitus (NIDDM) to decrease postprandial hyperglycemia, is to retard the absorption of glucose by inhibition of carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase, in the digestive organs. α-Glucosidase is the key enzyme catalyzing the final step in the digestive process of carbohydrates. Hence, α-glucosidase inhibitors can retard the liberation of d-glucose from dietary complex carbohydrates and delay glucose absorption, resulting in reduced postprandial plasma glucose levels and suppression of postprandial hyperglycemia. In recent years, many efforts have been made to identify effective α-glucosidase inhibitors from natural sources in order to develop a physiologic functional food or lead compounds for use against diabetes. Many α-glucosidase inhibitors that are phytoconstituents, such as flavonoids, alkaloids, terpenoids,anthocyanins, glycosides, phenolic compounds, and so on, have been isolated from plants. In the present review, we focus on the constituents isolated from different plants having α-glucosidase inhibitory potency along with IC50 values. [1] Objective: To review the effects of monotherapy with alpha-glucosidase inhibitors (AGIs) for patients with type 2 diabetes, with respect to mortality, morbidity, glycemic control, insulin levels, plasma lipids, body weight, and side effects. Research design and methods: We systematically searched the Cochrane Central register of Controlled Trials, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials, and reference lists, and we contacted experts and manufacturers. Inclusion criteria were randomized controlled trials of at least 12 weeks' duration, AGI monotherapy compared with any intervention, and one of the following outcome measures: mortality, morbidity, GHb, blood glucose, lipids, insulin levels, body weight, or side effects. Two independent reviewers assessed all abstracts, extracted all data, and assessed quality. We contacted all authors for data clarification. Continuous data were expressed as weighted mean differences and analyzed with a random-effects model. Possible influences of study characteristics and quality were assessed in sensitivity and meta-regression analyses. Results: Forty-one studies were included in the review (30 acarbose, 7 miglitol, 1 voglibose, and 3 combined), and heterogeneity was limited. We found no evidence for an effect on mortality or morbidity. Compared with placebo, AGIs had a beneficial effect on GHb (acarbose -0.77%; miglitol -0.68%), fasting and postload blood glucose and postload insulin. With acarbose dosages higher than 50 mg t.i.d., the effect on GHb was the same, but the occurrence of side effects increased. Acarbose decreased the BMI by 0.17 kg/m2 (95% CI 0.08-0.26). None of the AGIs had an effect on plasma lipids. Compared with sulfonylurea, AGIs seemed inferior with respect to glycemic control, but they reduced fasting and postload insulin levels. For comparisons with other agents, little data were available. Conclusions: We found no evidence for an effect on mortality or morbidity. AGIs have clear beneficial effects on glycemic control and postload insulin levels but not on plasma lipids. There is no need for dosages higher than 50 mg acarbose t.i.d. [2]

Solubility Data

Solubility (In Vitro)

H2O: 10 mg/mL

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)