Acarbose

Last updated

Acarbose
Haworth projection of acarbose.svg
Acarbose-3D-balls.png
Clinical data
Trade names Glucobay, Precose, Prandase
Other names(2R,3R,4R,5S,6R)-5-{[(2R,3R,4R,5S,6R)-5- {[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl- 5-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3- (hydroxymethyl)cyclohex-2-en-1-yl]amino} tetrahydro-2H-pyran-2-yl]oxy}-3,4-dihydroxy- 6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}- 6-(hydroxymethyl)tetrahydro-2H-pyran-2,3,4-triol
AHFS/Drugs.com Monograph
MedlinePlus a696015
License data
Pregnancy
category
  • AU:B3
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Extremely low
Metabolism Gastrointestinal tract
Elimination half-life 2 hours
Excretion Kidney (less than 2%)
Identifiers
  • O-4,6-Dideoxy-4-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1→4)-O-α-D-glucopyranosyl-(1→4)-D-glucopyranose
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.054.555 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C25H43NO18
Molar mass 645.608 g·mol−1
3D model (JSmol)
  • O([C@H]1[C@H](O)[C@@H](O)[C@H](O)O[C@@H]1CO)[C@H]4O[C@@H]([C@@H](O[C@H]3O[C@H](C)[C@@H](N[C@H]2/C=C(/CO)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]3O)[C@H](O)[C@H]4O)CO
  • InChI=1S/C25H43NO18/c1-6-11(26-8-2-7(3-27)12(30)15(33)13(8)31)14(32)19(37)24(40-6)43-22-10(5-29)42-25(20(38)17(22)35)44-21-9(4-28)41-23(39)18(36)16(21)34/h2,6,8-39H,3-5H2,1H3/t6-,8+,9-,10-,11-,12-,13+,14+,15+,16-,17-,18-,19-,20-,21-,22-,23-,24-,25-/m1/s1 Yes check.svgY
  • Key:XUFXOAAUWZOOIT-SXARVLRPSA-N Yes check.svgY
   (verify)

Acarbose (INN) [1] [2] is an anti-diabetic drug used to treat diabetes mellitus type 2 and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay (Bayer AG), in North America as Precose (Bayer Pharmaceuticals), and in Canada as Prandase (Bayer AG).

Contents

Acarbose is a starch blocker. It works by inhibiting alpha glucosidase, an intestinal enzyme that releases glucose from larger carbohydrates such as starch and sucrose. It is composed of an acarviosin moiety with a maltose at the reducing terminus. It can be degraded by a number of gut bacteria. [3]

Acarbose is cheap and popular in China, but not in the U.S. One physician explains that use in the U.S. is limited because it is not potent enough to justify the side effects of diarrhea and flatulence. [4] However, a large study concluded in 2013 that "acarbose is effective, safe and well tolerated in a large cohort of Asian patients with type 2 diabetes." [5] A possible explanation for the differing opinions is an observation that acarbose is significantly more effective in patients eating a relatively high-starch Eastern diet. [6]

Medical uses

Efficacy

In type II diabetic patients, acarbose averages an absolute decrease of 0.8 percentage points in HbA1c, which is a decrease of about 10% in typical HbA1c values in diabetes studies. [7] Individuals with higher baseline levels show higher reductions, about an 0.12% additional decrease for each point of baseline HbA1c. [7] Its effect on postprandial glucose, but not on HbA1c, scales with dose. [7] Among diabetic patients, acarbose may help reduce the damage done to blood vessels and kidneys by reducing glucose levels. [7]

A Cochrane systematic review assessed the effect of alpha-glucosidase inhibitors in people with prediabetes, defined as impaired glucose tolerance, impaired fasting blood glucose, elevated glycated hemoglobin A1c (HbA1c). [8] It was found that acarbose reduced the incidence of diabetes mellitus type 2 when compared to placebo, however there was no conclusive evidence that acarbose, when compared to diet and exercise, metformin, placebo, or no intervention, improved all-cause mortality, reduced or increased risk of cardiovascular mortality, serious or non-serious adverse events, non-fatal stroke, congestive heart failure, or non-fatal myocardial infarction. [8]

Several studies showed that glucosidase inhibitors and alpha-amylase inhibitors promote loss of visceral fat and waist by acting as calorie restriction mimetics (linked to its acarbose-like action). [9]

Combination therapy

The combination of acarbose with metformin results in greater reductions of HbA1c, fasting blood glucose and post-prandial glucose than either agent alone. [10]

Adverse effects

Since acarbose prevents the degradation of complex carbohydrates into glucose, some carbohydrate will remain in the intestine and be delivered to the colon. In the colon, bacteria digest (ferment) the complex carbohydrates, causing gastrointestinal side-effects such as flatulence (78% of patients) and diarrhea (14% of patients). Since these effects are dose-related, in general it is advised to start with a low dose and gradually increase the dose to the desired amount. One study found that gastrointestinal side effects decreased significantly (from 50% to 15%) over 24 weeks, even on constant dosing. [11] Sucrose is more likely to trigger GI side effects compared to starch. [7]

Acarbose is associated with very rare elevated transaminases (19 out of 500,000). [7] Even rarer cases of hepatitis has been reported with acarbose use. It usually goes away when the medicine is stopped. Liver enzymes should be checked before and during use of this medicine as a precaution. [12] A 2016 meta-analysis confirms that alpha-glucosidase inhibitors, including acarbose, have a statistically significant link to elevated transaminase levels. [13]

Pharmacology

Mechanism of action

Acarbose inhibits enzymes (glycoside hydrolases) needed to digest carbohydrates, specifically, alpha-glucosidase enzymes in the brush border of the small intestines, and pancreatic alpha-amylase. It locks up the enzymes by mimicking the transition state of the substrate with its amine linkage. [14] However, bacterial alpha-amylases from gut microbiome are able to degrade acarbose. [15] [16] [17]

Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, whereas the membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine. Inhibition of these enzyme systems reduces the rate of digestion of complex carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drug therapies is to decrease current blood glucose levels; the long-term effect is a reduction in HbA1c level. [18]

Metabolism

Acarbose degradation is the unique feature of glycoside hydrolases in gut microbiota, acarbose degrading glucosidase, which hydrolyze acarbose into an acarviosine-glucose and glucose. [17] Human enzymes do transform acarbose: the pancreatic alpha-amylase is able to perform a rearrangement reaction, moving the glucose unit in the "tail" maltose to the "head" of the molecule. Analog drugs with the "tail" glucose removed or flipped to an α(1-6) linkage resist this transformation. [14]

It has been reported that the maltogenic alpha-amylase from Thermus sp. IM6501 (ThMA) and a cyclodextrinase (CDase) from Streptococcus pyogenes could hydrolyse acarbose to glucose and acarviosine-glucose, ThMA can further hydrolyze acarviosine-glucose into acarviosin and glucose. [19] [20] A cyclomaltodextrinase (CDase) from gut bacteria Lactobacillus plantarum degraded acarbose via two different modes of action to produce maltose and acarviosin, as well as glucose and acarviosine-glucose, suggest that acarbose resistance is caused by the human microbiome. [3] The microbiome-derived acarbose kinases are also specific to phosphorylate and inactivate acarbose. [21] The molecular modeling showed the interaction between gut bacterial acarbose degrading glucosidase and human α-amylase. [22]

Acarbose is degraded by different enzymes in the gut microbiome Acarbose degradation in gut microbiome.jpg
Acarbose is degraded by different enzymes in the gut microbiome
Acarbose degradation by gut bacterial maltogenic amylase Acarbose degradation by gut bacterial maltogenic amylase.png
Acarbose degradation by gut bacterial maltogenic amylase

Natural distribution

In nature, acarbose is synthesized by soil bacteria Actinoplanes sp through its precursor valienamine. [23] And acarbose is also degraded by gut bacteria Lactobacillus plantarum and soil bacteria Thermus sp by acarbose degrading glucosidases.

In molecular biology

Acarbose is described chemically as a pseudotetrasaccharide, [24] specifically a maltotetraose mimic inhibitor. As an inhibitor that mimics some natural substrates, it is useful for elucidating the structure of sugar-digesting enzymes, by binding into the same pocket. [25]

Research

Most studies investigating alpha-glucosidase and alpha-amylase inhibitory activity use acarbose as reference. [26] [27]

In human T2DM patients, acarbose reduces total triglyceride levels. [28] Acarbose has a similar effect in non-T2DM patients with isolated familial hypertriglyceridemia. [7]

In smaller samples of healthy human volunteers, acarbose increases postprandial GLP-1 levels. [7]

In studies conducted by three independent laboratories by the US National Institute on Aging's intervention testing programme, acarbose was shown to extend the lifespan of female mice by 5% and of male mice by 22%. [29] [30]

Related Research Articles

<span class="mw-page-title-main">Amylase</span> Class of enzymes

An amylase is an enzyme that catalyses the hydrolysis of starch into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of starch but little sugar, such as rice and potatoes, may acquire a slightly sweet taste as they are chewed because amylase degrades some of their starch into sugar. The pancreas and salivary gland make amylase to hydrolyse dietary starch into disaccharides and trisaccharides which are converted by other enzymes to glucose to supply the body with energy. Plants and some bacteria also produce amylase. Specific amylase proteins are designated by different Greek letters. All amylases are glycoside hydrolases and act on α-1,4-glycosidic bonds.

<span class="mw-page-title-main">Hyperglycemia</span> Too much blood sugar, usually because of diabetes

Hyperglycemia or hyperglycaemia is the situation in which blood glucose level is higher than in a healthy subject. A fasting healthy human shows blood glucose level up to 5.6 mmol/L (100 mg/dL). After a meal (postprandial) containing carbohydrates, healthy subjects show postpandrial euglycemic peaks of less than 140 mg/dL (7.8 mmol/L). Therefore, fasting hyperglycemia are values of blood glucose higher than 5.6 mmol/L (100 mg/dL) whereas postprandial hyperglycemia are values higher than 140 mg/dL (7.8 mmol/L). Postprandial hyperglycemic levels as high as 155 mg/dL (8.6 mmol/L) at 1-h are associated with T2DM-related complications, which worsen as the degree of hyperglycemia increases. Patients with diabetes are oriented to avoid exceeding the recommended postprandial threshold of 160 mg/dL (8.89 mmol/L) for optimal glycemic control. Values of blood glucose higher than 160 mg/dL are classified as ‘very high’ hyperglycemia, a condition in which an excessive amount of glucose (glucotoxicity) circulates in the blood plasma. These values are higher than the renal threshold of 180 mg/dL (10 mmol/L) up to which glucose reabsorption is preserved at physiological rates and insulin therapy is not necessary. Blood glucose values higher than the cutoff level of 200 mg/dL (11.1 mmol/L) are used to diagnose T2DM and strongly associated with metabolic disturbances, although symptoms may not start to become noticeable until even higher values such as 13.9–16.7 mmol/L (~250–300 mg/dL). A subject with a consistent fasting blood glucose range between ~5.6 and ~7 mmol/L is considered slightly hyperglycemic, and above 7 mmol/L is generally held to have diabetes. For diabetics, glucose levels that are considered to be too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average, however, chronic levels above 10–12 mmol/L (180–216 mg/dL) can produce noticeable organ damage over time.

<span class="mw-page-title-main">Type 2 diabetes</span> Form of diabetes mellitus

Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Other symptoms include increased hunger, having a sensation of pins and needles, and sores (wounds) that heal slowly. Symptoms often develop slowly. Long-term complications from high blood sugar include heart disease, stroke, diabetic retinopathy, which can result in blindness, kidney failure, and poor blood flow in the lower-limbs, which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.

Drugs used in diabetes treat diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.

<span class="mw-page-title-main">Maltase</span> Enzyme

Maltase is an informal name for a family of enzymes that catalyze the hydrolysis of disaccharide maltose into two simple sugars of glucose. Maltases are found in plants, bacteria, yeast, humans, and other vertebrates.

<span class="mw-page-title-main">Digestive enzyme</span> Class of enzymes

Digestive enzymes take part in the chemical process of digestion, which follows the mechanical process of digestion. Food consists of macromolecules of proteins, carbohydrates, and fats that need to be broken down chemically by digestive enzymes in the mouth, stomach, pancreas, and duodenum, before being able to be absorbed into the bloodstream. Initial breakdown is achieved by chewing (mastication) and the use of digestive enzymes of saliva. Once in the stomach further mechanical churning takes place mixing the food with secreted gastric acid. Digestive gastric enzymes take part in some of the chemical process needed for absorption. Most of the enzymatic activity, and hence absorption takes place in the duodenum.

<span class="mw-page-title-main">Tagatose</span> Chemical compound

Tagatose is a hexose monosaccharide. It is found in small quantities in a variety of foods, and has attracted attention as an alternative sweetener. It is often found in dairy products, because it is formed when milk is heated. It is similar in texture and appearance to sucrose :215 and is 92% as sweet,:198 but with only 38% of the calories.:209 Tagatose is generally recognized as safe by the Food and Agriculture Organization and the World Health Organization, and has been since 2001. Since it is metabolized differently from sucrose, tagatose has a minimal effect on blood glucose and insulin levels. Tagatose is also approved as a tooth-friendly ingredient for dental products. Consumption of more than about 30 grams of tagatose in a dose may cause gastric disturbance in some people, as it is mostly processed in the large intestine, similar to soluble fiber.:214

Alpha-glucosidase inhibitors (AGIs) are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of carbohydrates. They are found in raw plants/herbs such as cinnamon and bacteria. Carbohydrates are normally converted into simple sugars (monosaccharides) by alpha-glucosidase enzymes present on cells lining the intestine, enabling monosaccharides to be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of dietary carbohydrates on blood sugar.

α-Glucosidase Enzyme

α-Glucosidase (EC 3.2.1.20, is a glucosidase located in the brush border of the small intestine that acts upon α bonds:

<span class="mw-page-title-main">Glycoside hydrolase</span> Class of enzymes which break glycosidic bonds via hydrolysis

In biochemistry, glycoside hydrolases are a class of enzymes which catalyze the hydrolysis of glycosidic bonds in complex sugars. They are extremely common enzymes, with roles in nature including degradation of biomass such as cellulose (cellulase), hemicellulose, and starch (amylase), in anti-bacterial defense strategies, in pathogenesis mechanisms and in normal cellular function. Together with glycosyltransferases, glycosidases form the major catalytic machinery for the synthesis and breakage of glycosidic bonds.

<span class="mw-page-title-main">Miglitol</span> Chemical compound

Miglitol is an oral alpha-glucosidase inhibitor used in the treatment of type 2 diabetes. It works by reversibly inhibiting alpha-glucosidase enzymes in the small intestine, which delays the digestion of complex carbohydrates and subsequently reduces postprandial glucose levels. Approved for clinical use since 1998, miglitol has demonstrated efficacy in improving glycemic control, reducing HbA1c levels, and decreasing both fasting and postprandial plasma glucose concentrations in long-term clinical trials. Additionally, recent studies have suggested that miglitol may have potential as an anti-obesity agent, showing promise in reducing body weight and body mass index in obese or diabetic patients. While generally well-tolerated, the most common side effects associated with miglitol are gastrointestinal disturbances, which are typically mild to moderate and tend to decrease over time.

<span class="mw-page-title-main">Voglibose</span> Alpha-glucosidase inhibitor

Voglibose is an alpha-glucosidase inhibitor used for lowering postprandial blood glucose levels in people with diabetes mellitus. Voglibose is a research product of Takeda Pharmaceutical Company, Japan's largest pharmaceutical company. Voglibose was discovered in 1981, and was first launched in Japan in 1994, under the trade name BASEN, to improve postprandial hyperglycemia in diabetes mellitus.

α-Amylase Enzyme that hydrolyses α bonds of large α-linked polysaccharides

α-Amylase is an enzyme that hydrolyses α bonds of large, α-linked polysaccharides, such as starch and glycogen, yielding shorter chains thereof, dextrins, and maltose, through the following biochemical process:

The enzyme cyclomaltodextrinase (EC 3.2.1.54) catalyzes the chemical reaction

<span class="mw-page-title-main">Glucosidases</span> Enzymes which hydrolyse glycosides

Glucosidases are the glycoside hydrolase enzymes categorized under the EC number 3.2.1.

<span class="mw-page-title-main">Maltase-glucoamylase</span> Enzyme

Maltase-glucoamylase, intestinal is an enzyme that in humans is encoded by the MGAM gene.

Prevention of type 2 diabetes can be achieved with both lifestyle changes and use of medication. The American Diabetes Association categorizes people with prediabetes, who have glycemic levels higher than normal but do not meet criteria for diabetes, as a high-risk group. Without intervention, people with prediabetes progress to type 2 diabetes with a 5% to 10% rate. Diabetes prevention is achieved through weight loss and increased physical activity, which can reduce the risk of diabetes by 50% to 60%.

<span class="mw-page-title-main">Alpha amylase inhibitor</span>

In molecular biology, alpha-amylase inhibitor is a protein family which inhibits mammalian alpha-amylases specifically, by forming a tight stoichiometric 1:1 complex with alpha-amylase. This family of inhibitors has no action on plant and microbial alpha amylases.

<span class="mw-page-title-main">Gemigliptin</span> Chemical compound

Gemigliptin (rINN), sold under the brand name Zemiglo, is an oral anti-hyperglycemic agent of the dipeptidyl peptidase-4 inhibitor class of drugs. Glucose lowering effects of DPP-4 inhibitors are mainly mediated by GLP-1 and gastric inhibitory polypeptide (GIP) incretin hormones which are inactivated by DPP-4.

<span class="mw-page-title-main">Glucan 1,4-alpha-maltohydrolase</span>

Glucan 1,4-alpha-maltohydrolase is an enzyme with systematic name 4-alpha-D-glucan alpha-maltohydrolase. This enzyme catalyses the following chemical reaction

References

  1. ↑ Elks J, Ganellin CR, eds. (1990). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 1–. doi:10.1007/978-1-4757-2085-3. ISBN   978-1-4757-2085-3.
  2. ↑ "International Nonproprietary Names for Pharmaceutical Substances. Recommended International Nonproprietary Names (Rec. INN): List 19" (PDF). World Health Organization. 1979. Retrieved 9 November 2016.
  3. 1 2 Jang MU, Kang HJ, Jeong CK, Kang Y, Park JE, Kim TJ (February 2018). "Functional expression and enzymatic characterization of Lactobacillus plantarum cyclomaltodextrinase catalyzing novel acarbose hydrolysis". Journal of Microbiology. 56 (2): 113–118. doi:10.1007/s12275-018-7551-3. PMID   29392561. S2CID   2660911.
  4. ↑ Kresge N (21 November 2011). "China's Thirst for New Diabetes Drugs Threatens Bayer's Lead". Bloomberg Business Week. Archived from the original on 21 November 2011. Retrieved 15 April 2016.
  5. ↑ Zhang W, Kim D, Philip E, Miyan Z, Barykina I, Schmidt B, et al. (April 2013). "A multinational, observational study to investigate the efficacy, safety and tolerability of acarbose as add-on or monotherapy in a range of patients: the Gluco VIP study". Clinical Drug Investigation. 33 (4): 263–274. doi:10.1007/s40261-013-0063-3. PMID   23435929. S2CID   207483590.
  6. ↑ Zhu Q, Tong Y, Wu T, Li J, Tong N (June 2013). "Comparison of the hypoglycemic effect of acarbose monotherapy in patients with type 2 diabetes mellitus consuming an Eastern or Western diet: a systematic meta-analysis". Clinical Therapeutics. 35 (6): 880–899. doi:10.1016/j.clinthera.2013.03.020. PMID   23602502.
  7. 1 2 3 4 5 6 7 8 DiNicolantonio JJ, Bhutani J, O'Keefe JH (2015). "Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes". Open Heart. 2 (1): e000327. doi:10.1136/openhrt-2015-000327. PMC   4620230 . PMID   26512331.
  8. 1 2 Moelands SV, Lucassen PL, Akkermans RP, De Grauw WJ, Van de Laar FA, et al. (Cochrane Metabolic and Endocrine Disorders Group) (December 2018). "Alpha-glucosidase inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus". The Cochrane Database of Systematic Reviews. 2018 (12): CD005061. doi:10.1002/14651858.CD005061.pub3. PMC   6517235 . PMID   30592787.
  9. ↑ Smith DL, Orlandella RM, Allison DB, Norian LA (June 2021). "Diabetes medications as potential calorie restriction mimetics-a focus on the alpha-glucosidase inhibitor acarbose". GeroScience. 43 (3): 1123–1133. doi:10.1007/s11357-020-00278-x. PMC   8190416 . PMID   33006707.
  10. ↑ Hedrington MS, Davis SN (December 2019). "Considerations when using alpha-glucosidase inhibitors in the treatment of type 2 diabetes". Expert Opinion on Pharmacotherapy. 20 (18): 2229–2235. doi:10.1080/14656566.2019.1672660. PMID   31593486. S2CID   203985605.
  11. ↑ Hoffmann J, Spengler M (December 1997). "Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: the Essen-II Study". The American Journal of Medicine. 103 (6): 483–490. doi:10.1016/S0002-9343(97)00252-0. PMID   9428831.
  12. ↑ "Acarbose: hepatitis: France, Spain". WHO Pharmaceuticals Newsletter. 1999. Archived from the original on 15 October 2009.
  13. ↑ Zhang L, Chen Q, Li L, Kwong JS, Jia P, Zhao P, et al. (September 2016). "Alpha-glucosidase inhibitors and hepatotoxicity in type 2 diabetes: a systematic review and meta-analysis". Scientific Reports. 6 (1): 32649. Bibcode:2016NatSR...632649Z. doi: 10.1038/srep32649 . PMC   5011653 . PMID   27596383.
  14. 1 2 Li C, Begum A, Numao S, Park KH, Withers SG, Brayer GD (March 2005). "Acarbose rearrangement mechanism implied by the kinetic and structural analysis of human pancreatic alpha-amylase in complex with analogues and their elongated counterparts". Biochemistry. 44 (9): 3347–3357. doi:10.1021/bi048334e. PMID   15736945.
  15. ↑ Park KH, Kim MJ, Lee HS, Han NS, Kim D, Robyt JF (December 1998). "Transglycosylation reactions of Bacillus stearothermophilus maltogenic amylase with acarbose and various acceptors". Carbohydrate Research. 313 (3–4): 235–246. doi:10.1016/S0008-6215(98)00276-6. PMID   10209866.
  16. ↑ Oh SW, Jang MU, Jeong CK, Kang HJ, Park JM, Kim TJ (August 2008). "Modulation of hydrolysis and transglycosylation activity of Thermus maltogenic amylase by combinatorial saturation mutagenesis". Journal of Microbiology and Biotechnology. 18 (8): 1401–1407. PMID   18756100.
  17. 1 2 Kim TJ, Kim MJ, Kim BC, Kim JC, Cheong TK, Kim JW, et al. (April 1999). "Modes of action of acarbose hydrolysis and transglycosylation catalyzed by a thermostable maltogenic amylase, the gene for which was cloned from a Thermus strain". Applied and Environmental Microbiology. 65 (4): 1644–1651. Bibcode:1999ApEnM..65.1644K. doi:10.1128/AEM.65.4.1644-1651.1999. PMC   91232 . PMID   10103262.
  18. ↑ Drug Therapy in Nursing, 2nd Edition.
  19. ↑ Jang MU, Kang HJ, Jeong CK, Oh GW, Lee EH, Son BS, et al. (2017). "Functional expression and enzymatic characterization of cyclomaltodextrinase from Streptococcus pyogenes". Korean Journal of Microbiology. 53 (3): 208–215. doi:10.7845/kjm.2017.7062. ISSN   0440-2413.
  20. ↑ Baek JS, Kim HY, Abbott TP, Moon TW, Lee SB, Park CS, et al. (March 2003). "Acarviosine-simmondsin, a novel compound obtained from acarviosine-glucose and simmondsin by Thermus maltogenic amylase and its in vivo effect on food intake and hyperglycemia". Bioscience, Biotechnology, and Biochemistry. 67 (3): 532–539. doi: 10.1271/bbb.67.532 . PMID   12723600. S2CID   2813481.
  21. ↑ Balaich J, Estrella M, Wu G, Jeffrey PD, Biswas A, Zhao L, et al. (December 2021). "The human microbiome encodes resistance to the antidiabetic drug acarbose". Nature. 600 (7887): 110–115. Bibcode:2021Natur.600..110B. doi:10.1038/s41586-021-04091-0. PMC   10258454 . PMID   34819672. S2CID   244644880.
  22. ↑ Park KH (2006). "Function and Tertiary- and Quaternary-structure of Cyclodextrin-hydrolyzing Enzymes (CDase), a Group of Multisubstrate Specific Enzymes Belonging to the α-Amylase Family". Journal of Applied Glycoscience. 53 (1): 35–44. doi: 10.5458/jag.53.35 . ISSN   1344-7882. S2CID   86894203.
  23. ↑ Tsunoda T, Samadi A, Burade S, Mahmud T (June 2022). "Complete biosynthetic pathway to the antidiabetic drug acarbose". Nature Communications. 13 (1): 3455. Bibcode:2022NatCo..13.3455T. doi:10.1038/s41467-022-31232-4. PMC   9200736 . PMID   35705566.
  24. ↑ Bozonnet S, Jensen MT, Nielsen MM, Aghajari N, Jensen MH, Kramhøft B, et al. (October 2007). "The 'pair of sugar tongs' site on the non-catalytic domain C of barley alpha-amylase participates in substrate binding and activity". The FEBS Journal. 274 (19): 5055–5067. doi:10.1111/j.1742-4658.2007.06024.x. PMID   17803687. S2CID   25592455.
  25. ↑ Miyazaki T, Park EY (June 2020). "Structure-function analysis of silkworm sucrose hydrolase uncovers the mechanism of substrate specificity in GH13 subfamily 17 exo-α-glucosidases". The Journal of Biological Chemistry. 295 (26): 8784–8797. doi: 10.1074/jbc.RA120.013595 . PMC   7324511 . PMID   32381508.
  26. ↑ Moreira FD, Reis CE, Gallassi AD, Moreira DC, Welker AF (9 October 2024). Dardari D (ed.). "Suppression of the postprandial hyperglycemia in patients with type 2 diabetes by a raw medicinal herb powder is weakened when consumed in ordinary hard gelatin capsules: A randomized crossover clinical trial". PLOS ONE. 19 (10): e0311501. Bibcode:2024PLoSO..1911501M. doi: 10.1371/journal.pone.0311501 . PMC   11463819 . PMID   39383145. Creative Commons by small.svg  This article incorporates textfrom this source, which is available under the CC BY 4.0 license.
  27. ↑ Hayward NJ, McDougall GJ, Farag S, Allwood JW, Austin C, Campbell F, et al. (December 2019). "Cinnamon Shows Antidiabetic Properties that Are Species-Specific: Effects on Enzyme Activity Inhibition and Starch Digestion". Plant Foods for Human Nutrition. 74 (4): 544–552. doi:10.1007/s11130-019-00760-8. PMC   6900266 . PMID   31372918.
  28. ↑ Yousefi M, Fateh ST, Nikbaf-Shandiz M, Gholami F, Rastgoo S, Bagher R, et al. (November 2023). "The effect of acarbose on lipid profiles in adults: a systematic review and meta-analysis of randomized clinical trials". BMC Pharmacology & Toxicology. 24 (1): 65. doi: 10.1186/s40360-023-00706-6 . PMC   10664642 . PMID   37990256.
  29. ↑ Harrison DE, Strong R, Allison DB, Ames BN, Astle CM, Atamna H, et al. (April 2014). "Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males". Aging Cell. 13 (2): 273–282. doi:10.1111/acel.12170. PMC   3954939 . PMID   24245565.
  30. ↑ Ladiges W, Liggitt D (2017). "Testing drug combinations to slow aging". Pathobiology of Aging & Age Related Diseases. 8 (1): 1407203. doi:10.1080/20010001.2017.1407203. PMC   5706479 . PMID   29291036.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.