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Glibenclamide
Glibenclamide, also known as glyburide, is an antidiabetic medication used to treat type 2 diabetes. It is recommended that it be taken together with diet and exercise. It may be used with other antidiabetic medication. It is not recommended for use by itself in type 1 diabetes. It is taken by mouth. Common side effects include nausea and heartburn. Serious side effects may include angioedema and low blood sugar. It is generally not recommended during pregnancy but can be used during breastfeeding. It is in the sulfonylureas class of medications and works by increasing the release of insulin from the pancreas. Glibenclamide was discovered in 1969 and approved for medical use in the United States in 1984. It is available as a generic medication. In 2022, it was the 200th most commonly prescribed medication in the United States, with more than 2million prescriptions. Medical uses Glibenclamide is indicated as an adjunct to diet and exercise to improve glycemic control in ...
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Metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is not associated with weight gain and is taken by mouth. It is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotics. Metformin is generally well tolerated. Common adverse effects include diarrhea, nausea, and abdominal pain. It has a small risk of causing low blood sugar. High blood lactic acid level is a concern if the medication is used in overly large doses or prescribed in people with severe kidney problems. It is not recommended in those with significant liver disease. Metformin is a biguanide antihyperglycemic agent. It works by decreasing glucose production in the liver, increasing the insulin sensitivity of body tissues, and increasing GDF15 secretion, which redu ...
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CYP2C9
Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the ''CYP2C9'' gene. The gene is highly polymorphic, which affects the efficiency of the metabolism by the enzyme. Function CYP2C9 is a crucial cytochrome P450 enzyme, which plays a significant role in the metabolism, by oxidation, of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes. The protein is mainly expressed in liver, duodenum and small intestine. About 100 therapeutic drugs are metabolized by CYP2C9, including drugs with a narrow therapeutic index such as warfarin and phenytoin, and other routinely prescribed drugs such as acenocoumarol, tolbutamide, losartan, glipizide, and some nonsteroidal anti-inflammatory drugs. By contrast, the known extr ...
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Sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas. A number of sulfonylureas are also used as herbicides, because they can interfere with plant biosynthesis of certain amino acids. Sulfonylureas are also used experimentally to inhibit interleukin 1 beta release from the NALP3 (or NLRP3) inflammasome. Drugs * First-generation drugs include acetohexamide, carbutamide, chlorpropamide, glycyclamide (tolcyclamide), metahexamide, tolazamide and tolbutamide. * Second-generation drugs include glibenclamide (glyburide), glibornuride, gliclazide, glipizide, gliquidone, glisoxepide and glyclopyramide. * Third-generation drugs include glimepiride, although it is sometimes considered a second-generation agent. Medical uses Sulfonylureas are used primarily for the treatment of d ...
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Antidiabetic Medication
Drugs used in diabetes treat diabetes mellitus by altering the glucose level in the blood. With the exceptions of insulin, most GLP receptor agonists (liraglutide, exenatide, and others), and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors. Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in type 1, which must be injected. Diabetes mellitus type 2 is a disease of insulin resistance by cells. Type 2 diabetes mellitus is the most common type of diabetes. Treatments include agents that (1) increase the amount of insulin secreted by the pancreas, (2) increase the sensitivity of target organs to insulin, (3) decrease the rate at which glucose is absorbed from the gastrointestinal tract, and (4) incre ...
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ATP-sensitive Potassium Channel
An ATP-sensitive potassium channel (or KATP channel) is a type of potassium channel that is gated by intracellular nucleotides, ATP and ADP. ATP-sensitive potassium channels are composed of Kir6.x-type subunits and sulfonylurea receptor (SUR) subunits, along with additional components. KATP channels are found in the plasma membrane; however some may also be found on subcellular membranes. These latter classes of KATP channels can be classified as being either sarcolemmal ("sarcKATP"), mitochondrial ("mitoKATP"), or nuclear ("nucKATP"). Discovery and structure KATP channels were first identified in cardiac myocytes by the Akinori Noma group in Japan. They have also been found in pancreas where they control insulin secretion, but are in fact widely distributed in plasma membranes. SarcKATP are composed of eight protein subunits (octamer). Four of these are members of the inward-rectifier potassium ion channel family Kir6.x (either Kir6.1 or Kir6.2), while the other four ar ...
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Oral Administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are intended to have a systemic effect, reaching different parts of the body via the bloodstream, for example. Oral administration can be easier and less painful than other routes, such as injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients willing and able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth ...
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ABCC8
ATP-binding cassette transporter sub-family C member 8 is a protein that in humans is encoded by the ''ABCC8'' gene. ''ABCC8'' orthologs have been identified in all mammals for which complete genome data are available. The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a modulator of ATP-sensitive potassium channels and insulin release. Mutations and deficiencies in this protein have been observed in patients with hyperinsulinemic hypoglycemia of infancy, an autosomal recessive disorder of unregulated and high insulin secretion. Mutations have also been associated with non-insulin-dependent diabetes mellitus type II (neonatal dia ...
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G6PD Deficiency
Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. Following a specific trigger, symptoms such as yellowish skin, dark urine, shortness of breath, and feeling tired may develop. Complications can include anemia and newborn jaundice. Some people never have symptoms. It is an X-linked recessive disorder that results in defective glucose-6-phosphate dehydrogenase enzyme. Glucose-6-phosphate dehydrogenase is an enzyme which protects red blood cells, which carry oxygen from the lungs to tissues throughout the body. A defect of the enzyme results in the premature breakdown of red blood cells. This destruction of red blood cells is called hemolysis. Red blood cell breakdown may be triggered by infections, certain medication, stress, or foods such as fava beans. Depending on the specific mutatio ...
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Hemolysis
Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo or in vitro. One cause of hemolysis is the action of hemolysins, toxins that are produced by certain pathogenic bacteria or fungi. Another cause is intense physical exercise. Hemolysins damage the red blood cell's cytoplasmic membrane, causing lysis and eventually cell death. Etymology From hemo- + -lysis, from , "blood") + , "loosening"). Inside the body Hemolysis inside the body can be caused by a large number of medical conditions, including some parasites (''e.g.'', ''Plasmodium''), some autoimmune disorders (''e.g.'', autoimmune haemolytic anaemia, drug-induced hemolytic anemia, atypical hemolytic uremic syndrome (aHUS)), some genetic disorders (''e.g.'', Sickle-cell disease or G6PD deficiency), or blood with too low a solute conc ...
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Voltage-dependent Calcium Channel
Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca2+. These channels are slightly permeable to sodium ions, so they are also called Ca2+-Na+ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. At physiologic or resting membrane potential, VGCCs are normally closed. They are activated (''i.e.'': opened) at depolarized membrane potentials and this is the source of the "voltage-gated" epithet. The concentration of calcium (Ca2+ ions) is normally several thousand times higher outside the cell than inside. Activation of particular VGCCs allows a Ca2+ influx into the cell, which, depending on the cell type, results in activation of calcium-sensitive potassium channels, muscular contraction, e ...
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Beta Cell
Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are diminished, leading to insufficient insulin secretion and hyperglycemia. Function The primary function of a beta cell is to produce and release insulin and amylin. Both are hormones which reduce blood glucose levels by different mechanisms. Beta cells can respond quickly to spikes in blood glucose concentrations by secreting some of their stored insulin and amylin while simultaneously producing more. Primary cilia on beta cells regulate their function and energy metabolism. Cilia deletion can lead to islet dysfunction and type 2 diabetes. Insulin synthesis Beta cells are the only site of insulin synthesis in mammals. As glucose stimulates insulin secretion, it simultaneously increases proinsulin biosynthesis, mainly through translational cont ...
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Depolarization
In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is essential to the function of many cells, communication between cells, and the overall physiology of an organism. Most cells in higher organisms maintain an internal environment that is negatively charged relative to the cell's exterior. This difference in charge is called the cell's membrane potential. In the process of depolarization, the negative internal charge of the cell temporarily becomes more positive (less negative). This shift from a negative to a more positive membrane potential occurs during several processes, including an action potential. During an action potential, the depolarization is so large that the potential difference across the cell membrane briefly reverses polarity, with the inside of the cell becoming positively char ...
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