Product Code Database
Acarbose (INN) (1990). 9781475720853, Springer. ISBN 9781475720853 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), in North America as Precose (Bayer), and in Canada as Prandase (Bayer).
Acarbose is a starch blocker. It works by inhibiting alpha glucosidase, an intestinal enzyme that releases glucose from larger 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.
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. 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." 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.
A Cochrane systematic review assessed the effect of alpha-glucosidase inhibitors in people with prediabetes, defined as impaired glucose tolerance, impaired Glucose test, elevated glycated hemoglobin A1c (HbA1c). 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 Mortality rate, reduced or increased risk of cardiovascular mortality, serious or non-serious adverse events, non-fatal stroke, Heart failure, or non-fatal myocardial infarction.
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).
Acarbose is associated with very rare elevated transaminases (19 out of 500,000). 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. A 2016 meta-analysis confirms that alpha-glucosidase inhibitors, including acarbose, have a statistically significant link to elevated transaminase levels.
Pancreas alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, whereas the membrane-bound intestinal alpha-glucosidases hydrolyze , , and to glucose and other 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. Drug Therapy in Nursing, 2nd Edition.
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. 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. The microbiome-derived acarbose kinases are also specific to phosphorylate and inactivate acarbose. The molecular modeling showed the interaction between gut bacterial acarbose degrading glucosidase and human α-amylase.
In human T2DM patients, acarbose reduces total triglyceride levels. Acarbose has a similar effect in non-T2DM patients with isolated familial hypertriglyceridemia.
In smaller samples of healthy human volunteers, acarbose increases postprandial GLP-1 levels.
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%.
Pharmacology
Mechanism of action
Acarbose inhibits enzymes (glycoside hydrolases) needed to digest , 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. However, bacterial alpha-amylases from gut microbiome are able to degrade acarbose.
Metabolism
Acarbose degradation is the unique feature of glycoside hydrolases in gut microbiota, acarbose degrading Glucosidases, which hydrolyze acarbose into an acarviosine-glucose and glucose. 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.
Natural distribution
In nature, acarbose is synthesized by soil bacteria Actinoplanes sp through its precursor valienamine.
In molecular biology
Acarbose is described chemically as a pseudotetrasaccharide, 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.
Research
Most studies investigating alpha-glucosidase and alpha-amylase inhibitory activity use acarbose as reference.
|
|
