Alpha-glucosidase inhibitor
Encyclopedia
Alpha-glucosidase inhibitors are oral anti-diabetic drug
s 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 (monosaccharide
s), which can be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of carbohydrates on blood sugar
.
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.
For example, research has shown the culinary mushroom Maitake (Grifola frondosa) has a hypoglycemic
effect. The reason Maitake lowers blood sugar is because the mushroom naturally contains a alpha glucosidase inhibitor.http://www.ncbi.nlm.nih.gov/pubmed/12224646
Another plant attracting a lot of attention is Salacia oblonga
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.
Alpha-glucosidase inhibitors may also be useful in patients with diabetes mellitus type 1
; however, this use has not been officially approved by the Food and Drug Administration
.
s: specifically alpha-glucosidase
enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidase
s hydrolyze oligosaccharide
s, trisaccharides, and disaccharide
s 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.
, 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.
Voglibose, in contrast to acarbose, has less of these side effects, and is hence preferred lately. It is also more economical compared to acarbose.
Pneumatosis Cystoides Intestinalis is another reported side effect.
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.
Anti-diabetic drug
Anti-diabetic medications treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents...
s used for diabetes mellitus type 2
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
that work by preventing the digestion of carbohydrates (such as starch
Starch
Starch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...
and table sugar
Sucrose
Sucrose is the organic compound commonly known as table sugar and sometimes called saccharose. A white, odorless, crystalline powder with a sweet taste, it is best known for its role in human nutrition. The molecule is a disaccharide composed of glucose and fructose with the molecular formula...
). Carbohydrates are normally converted into simple sugars (monosaccharide
Monosaccharide
Monosaccharides are the most basic units of biologically important carbohydrates. They are the simplest form of sugar and are usually colorless, water-soluble, crystalline solids. Some monosaccharides have a sweet taste. Examples of monosaccharides include glucose , fructose , galactose, xylose...
s), which can be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of carbohydrates on blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
.
Examples and differences
Examples of alpha-glucosidase inhibitors include:- AcarboseAcarboseAcarbose is an anti-diabetic drug used to treat type 2 diabetes mellitus and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay , in North America as Precose , and in Canada as Prandase...
- Precose - Miglitol - Glyset
- VogliboseVogliboseVoglibose is an alpha-glucosidase inhibitor used for lowering post-prandial blood glucose levels in people with diabetes mellitus. Voglibose delays the absorption of glucose thereby reduces the risk of macrovascular complications...
Even though the drugs have a similar mechanism of action, there are subtle differences between acarbose and miglitol. Acarbose is an oligosaccharide
Oligosaccharide
An oligosaccharide is a saccharide polymer containing a small number of component sugars, also known as simple sugars...
, whereas miglitol resembles a monosaccharide
Monosaccharide
Monosaccharides are the most basic units of biologically important carbohydrates. They are the simplest form of sugar and are usually colorless, water-soluble, crystalline solids. Some monosaccharides have a sweet taste. Examples of monosaccharides include glucose , fructose , galactose, xylose...
. Miglitol is fairly well absorbed by the body, as opposed to acarbose. Moreover, acarbose inhibits pancreatic alpha-amylase in addition to alpha-glucosidase.
Natural alpha glucosidase inhibitors
There are a large number of plants with Alpha-glucosidase inhibitor action.,For example, research has shown the culinary mushroom Maitake (Grifola frondosa) has a hypoglycemic
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
effect. The reason Maitake lowers blood sugar is because the mushroom naturally contains a alpha glucosidase inhibitor.http://www.ncbi.nlm.nih.gov/pubmed/12224646
Another plant attracting a lot of attention is Salacia oblonga
Role in clinical use
Alpha-glucosidaseAlpha-glucosidase
Alpha-glucosidase is a glucosidase acting upon 1,4-alpha bonds. This is in contrast to beta-glucosidase.The term maltase, which refers to an enzyme cleaving maltose, is nearly equivalent.Types include:* Acid alpha-glucosidase* neutral** GANAB** GANC...
inhibitors are used to establish greater glycemic control over hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
in diabetes mellitus type 2
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
, particularly with regard to postprandial
Postprandial
Postprandial means after eating a meal while preprandial is before a meal.-Usages of the term:This term is used in many contexts but also in relation to blood sugar levels, which are normally measured 2 hours after and before eating in a postprandial glucose test...
hyperglycemia. They may be used as monotherapy in conjunction with an appropriate diabetic diet
Diabetic diet
There is much controversy regarding what diet to recommend to sufferers of diabetes mellitus. The diet most often recommended is high in dietary fiber, especially soluble fiber, but low in fat . Recommendations of the fraction of total calories to be obtained from carbohydrate intake range from 1/6...
and exercise, or they may be used in conjunction with other anti-diabetic drugs.
Alpha-glucosidase inhibitors may also be useful in patients with diabetes mellitus type 1
Diabetes mellitus type 1
Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose...
; however, this use has not been officially approved by the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
.
Mechanism of action
Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrateCarbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
s: specifically alpha-glucosidase
Alpha-glucosidase
Alpha-glucosidase is a glucosidase acting upon 1,4-alpha bonds. This is in contrast to beta-glucosidase.The term maltase, which refers to an enzyme cleaving maltose, is nearly equivalent.Types include:* Acid alpha-glucosidase* neutral** GANAB** GANC...
enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidase
Alpha-glucosidase
Alpha-glucosidase is a glucosidase acting upon 1,4-alpha bonds. This is in contrast to beta-glucosidase.The term maltase, which refers to an enzyme cleaving maltose, is nearly equivalent.Types include:* Acid alpha-glucosidase* neutral** GANAB** GANC...
s hydrolyze oligosaccharide
Oligosaccharide
An oligosaccharide is a saccharide polymer containing a small number of component sugars, also known as simple sugars...
s, trisaccharides, and disaccharide
Disaccharide
A disaccharide or biose is the carbohydrate formed when two monosaccharides undergo a condensation reaction which involves the elimination of a small molecule, such as water, from the functional groups only. Like monosaccharides, disaccharides form an aqueous solution when dissolved in water...
s to glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
and other monosaccharides in the small intestine.
Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases. Pancreatic alpha-amylase
Alpha-Amylase
α-Amylase is an enzyme that hydrolyses alpha-bonds of large alpha-linked polysaccharides such as starch and glycogen, yielding glucose and maltose. It is the major form of amylase found in humans and other mammals...
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
Glycosylated hemoglobin
Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose...
level.
Dosing
Since alpha-glucosidase inhibitors are competitive inhibitors of the 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 & precautions
Since alpha-glucosidase inhibitors prevent the degradation of complex carbohydrates into glucose, the carbohydrates will remain in the intestine. In the colonColon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
, bacteria will digest the complex carbohydrates, thereby causing gastrointestinal side effects such as flatulence
Flatulence
Flatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
and diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
. 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.
Voglibose, in contrast to acarbose, has less of these side effects, and is hence preferred lately. It is also more economical compared to acarbose.
Pneumatosis Cystoides Intestinalis is another reported side effect.
If a patient using an alpha-glucosidase inhibitor suffers from an episode of hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
, 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.