Biology:Alpha-glucosidase inhibitor
Alpha-glucosidase inhibitors (AGIs) are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of carbohydrates (such as starch and table sugar). 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.
Examples and differences
Examples of alpha-glucosidase inhibitors include:
Even though the drugs have a similar mechanism of action, there are subtle differences between acarbose and miglitol. Acarbose is an oligosaccharide, whereas miglitol resembles a monosaccharide. Miglitol is fairly well absorbed by the body, as opposed to acarbose. Moreover, acarbose inhibits pancreatic alpha-amylase in addition to alpha-glucosidase, and is degraded by gut bacterial maltogenic alpha-amylase and cyclomaltodextrinase.[1][2]
Natural alpha glucosidase inhibitors
There are a large number of natural products with alpha-glucosidase inhibitor action.[3][4]
For example, research has shown the culinary mushroom Maitake (Grifola frondosa) has a hypoglycemic effect.[5][6][7][8][9][10] The reason Maitake lowers blood sugar is because the mushroom naturally contains an alpha glucosidase inhibitor.[11] Another plant attracting a lot of attention is Salacia oblonga.[12]
Clinical use
Alpha-glucosidase inhibitors are used to establish greater glycemic control over hyperglycemia in diabetes mellitus type 2, particularly with regard to postprandial hyperglycemia. They may be used as monotherapy in conjunction with an appropriate diabetic diet and exercise, or they may be used in conjunction with other anti-diabetic drugs.
A Cochrane systematic review assessed the effect of AGIs in people with impaired glucose tolerance, impaired fasting blood glucose, elevated glycated hemoglobin A1c (HbA1c).[13] It was found that Acarbose appeared to reduce incidence of diabetes mellitus type 2 when compared to placebo, however there was no conclusive evidence that acarbose compare to diet and exercise, metformin, placebo, no intervention improved all-cause mortality, reducer or increased risk of cardiovascular mortality, serious or non-serious adverse events, non-fatal stroke, congestive heart failure, or non-fatal myocardial infarction.[13] The same review found that there was no conclusive evidence that voglibose compared to diet and exercise or placebo reduced incidence of diabetes mellitus type 2, or any of the other measured outcomes.[13]
In patients with diabetes mellitus type 1, alpha-glucosidase inhibitors use has not been officially approved by the Food and Drug Administration in the US but some data exists on the effectiveness in this population, showing potential benefits weighted against an increased risk of hypoglycemia.[14]
Mechanism of action
Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrates: specifically alpha-glucosidase enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine.
Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine.
Inhibition of these enzyme systems reduces the rate of digestion of carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels: the long-term effect is a small reduction in hemoglobin A1c level.[15]
Dosing
Since alpha-glucosidase inhibitors are competitive inhibitors of digestive enzymes, they must be taken at the start of main meals to have maximal effect. Their effects on blood sugar levels following meals will depend on the amount of complex carbohydrates in the meal.
Side effects and precautions
Since alpha-glucosidase inhibitors prevent the degradation of complex carbohydrates into glucose, the carbohydrates will remain in the intestine. In the colon, bacteria will digest the complex carbohydrates, thereby causing gastrointestinal side effects such as flatulence and diarrhea. Since these effects are dose-related, it is generally advised to start with a low dose and gradually increase the dose to the desired amount. Pneumatosis cystoides intestinalis is another reported side effect.[citation needed] If a patient using an alpha-glucosidase inhibitor suffers from an episode of hypoglycemia, the patient should eat something containing monosaccharides, such as glucose tablets. Since the drug will prevent the digestion of polysaccharides (or non-monosaccharides), non-monosaccharide foods may not effectively reverse a hypoglycemic episode in a patient taking an alpha-glucosidase inhibitor.[citation needed]
See also
References
- ↑ "Functional expression and enzymatic characterization of Lactobacillus plantarum cyclomaltodextrinase catalyzing novel acarbose hydrolysis". Journal of Microbiology 56 (2): 113–118. February 2018. doi:10.1007/s12275-018-7551-3. PMID 29392561.
- ↑ "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. April 1999. doi:10.1128/AEM.65.4.1644-1651.1999. PMID 10103262.
- ↑ "Antidiabetic medicinal plants as a source of alpha glucosidase inhibitors". Current Diabetes Reviews 6 (4): 247–254. July 2010. doi:10.2174/157339910791658826. PMID 20522017.
- ↑ "[Development of alpha-glucosidase inhibitor from medicinal herbs]" (in zh). Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica 35 (12): 1633–1640. June 2010. doi:10.4268/cjcmm20101229. PMID 20815224.
- ↑ "A possible hypoglycaemic effect of maitake mushroom on Type 2 diabetic patients". Diabetic Medicine 18 (12): 1010. December 2001. doi:10.1046/j.1464-5491.2001.00532-5.x. PMID 11903406.
- ↑ "Anti-diabetic effect of an alpha-glucan from fruit body of maitake (Grifola frondosa) on KK-Ay mice". The Journal of Pharmacy and Pharmacology 59 (4): 575–582. April 2007. doi:10.1211/jpp.59.4.0013. PMID 17430642.
- ↑ "Anti-diabetic activity present in the fruit body of Grifola frondosa (Maitake). I". Biological & Pharmaceutical Bulletin 17 (8): 1106–1110. August 1994. doi:10.1248/bpb.17.1106. PMID 7820117.
- ↑ "Submerged culture mycelium and broth of Grifola frondosa improve glycemic responses in diabetic rats". The American Journal of Chinese Medicine 36 (2): 265–285. 2008. doi:10.1142/S0192415X0800576X. PMID 18457360.
- ↑ "Effects of a water-soluble extract of maitake mushroom on circulating glucose/insulin concentrations in KK mice". Diabetes, Obesity & Metabolism 4 (1): 43–48. January 2002. doi:10.1046/j.1463-1326.2002.00180.x. PMID 11874441.
- ↑ "Maitake (Grifola frondosa) improve glucose tolerance of experimental diabetic rats". Journal of Nutritional Science and Vitaminology 47 (1): 57–63. February 2001. doi:10.3177/jnsv.47.57. PMID 11349892.
- ↑ "Alpha-glucosidase inhibitor from the seeds of balsam pear (Momordica charantia) and the fruit bodies of Grifola frondosa". Bioscience, Biotechnology, and Biochemistry 66 (7): 1576–1578. July 2002. doi:10.1271/bbb.66.1576. PMID 12224646.
- ↑ Vyas N, Mehra R, Makhija R. Salacia - The new multi-targeted approach in diabetics. Ayu. 2016;37(2):92-97. doi:10.4103/ayu.AYU_134_13
- ↑ 13.0 13.1 13.2 Moelands, Suzanne VL; Lucassen, Peter LBJ; Akkermans, Reinier P; De Grauw, Wim JC; Van de Laar, Floris A (2018-12-28). Cochrane Metabolic and Endocrine Disorders Group. ed. "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" (in en). Cochrane Database of Systematic Reviews 2018 (12). doi:10.1002/14651858.CD005061.pub3. PMID 30592787. PMC 6517235. https://doi.wiley.com/10.1002/14651858.CD005061.pub3.
- ↑ Alternative Agents in Type 1 Diabetes in Addition to Insulin Therapy: Metformin, Alpha-Glucosidase Inhibitors, Pioglitazone, GLP-1 Agonists, DPP-IV Inhibitors, and SGLT-2 Inhibitors. Michelle DeGeeter, PharmD, CDE, Bobbie Williamson, PharmD, BCACP, CDE. Journal of Pharmacy Practice Vol 29, Issue 2, pp. 144 - 159. First Published October 13, 2014 https://doi.org/10.1177/0897190014549837
- ↑ Drug Therapy In Nursing. Hagerstown, MD: Lippincott Williams & Wilkins. 2006. ISBN 0-7817-4839-9. https://archive.org/details/drugtherapyinnur00asch.[page needed]
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