SGLT2
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SGLT2
The sodium/glucose cotransporter 2 (SGLT2) is a protein that in humans is encoded by the (solute carrier family 5 (sodium/glucose cotransporter)) gene. Function SGLT2 is a member of the sodium glucose cotransporter family, which are sodium-dependent glucose transport proteins. SGLT2 is the major cotransporter involved in glucose reabsorption in the kidney. SGLT2 is located in the early proximal tubule, and is responsible for reabsorption of 80-90% of the glucose filtered by the kidney glomerulus. Most of the remaining glucose absorption is by sodium/glucose cotransporter 1 (SGLT1) in more distal sections of the proximal tubule. SGLT2 inhibitors for diabetes SGLT2 inhibitors are called gliflozins. They lead to a reduction in blood glucose levels, and therefore have potential use in the treatment of type II diabetes. Gliflozins enhance glycemic control as well as reduce body weight and systolic and diastolic blood pressure. The gliflozins canagliflozin, dapagliflozin, and ...
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SGLT2 Inhibitor
SGLT2 inhibitors, also called gliflozins or flozins, are a class of medications that modulate sodium-glucose transport proteins in the nephron (the functional units of the kidney), unlike SLC5A1, SGLT1 inhibitors that perform a similar function in the intestinal mucosa. The foremost metabolic effect of this is to inhibit renal glucose reabsorption, reabsorption of glucose in the kidney and therefore lower blood sugar. They act by inhibiting sodium-glucose transport protein 2 (SGLT2). SGLT2 inhibitors are used in the treatment of type II diabetes mellitus (T2DM). Apart from blood sugar control, gliflozins have been shown to provide significant cardiovascular benefit in patients with type II diabetes (T2DM). Several medications of this class have been approved or are currently under development. In studies on canagliflozin, a member of this class, the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure. Medical us ...
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Gliflozins
SGLT2 inhibitors, also called gliflozins or flozins, are a class of medications that modulate sodium-glucose transport proteins in the nephron (the functional units of the kidney), unlike SGLT1 inhibitors that perform a similar function in the intestinal mucosa. The foremost metabolic effect of this is to inhibit reabsorption of glucose in the kidney and therefore lower blood sugar. They act by inhibiting sodium-glucose transport protein 2 (SGLT2). SGLT2 inhibitors are used in the treatment of type II diabetes mellitus (T2DM). Apart from blood sugar control, gliflozins have been shown to provide significant cardiovascular benefit in patients with type II diabetes (T2DM). Several medications of this class have been approved or are currently under development. In studies on canagliflozin, a member of this class, the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure. Medical uses The 2022 ADA standards of medi ...
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Sodium-glucose Transport Proteins
Sodium-dependent glucose cotransporters (or sodium-glucose linked transporter, SGLT) are a family of glucose transporter found in the intestinal mucosa (enterocytes) of the small intestine (SGLT1) and the proximal tubule of the nephron (SGLT2 in PCT and SGLT1 in PST). They contribute to renal glucose reabsorption. In the kidneys, 100% of the filtered glucose in the glomerulus has to be reabsorbed along the nephron (98% in PCT, via SGLT2). If the plasma glucose concentration is too high (hyperglycemia), glucose passes into the urine (glucosuria) because SGLT are saturated with the filtered glucose. Types The two most well known members of SGLT family are SGLT1 and SGLT2, which are members of the SLC5A gene family. In addition to SGLT1 and SGLT2, there are 10 other members in the human protein family SLC5A. Of these, SLC5A4/SGLT3 (SAAT1) is a low-affinity transporter for glucose, but seems to have more of an electric function. The other SLC5 proteins transport mannose, my ...
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Glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using energy from sunlight, where it is used to make cellulose in cell walls, the most abundant carbohydrate in the world. In energy metabolism, glucose is the most important source of energy in all organisms. Glucose for metabolism is stored as a polymer, in plants mainly as starch and amylopectin, and in animals as glycogen. Glucose circulates in the blood of animals as blood sugar. The naturally occurring form of glucose is -glucose, while -glucose is produced synthetically in comparatively small amounts and is less biologically active. Glucose is a monosaccharide containing six carbon atoms and an aldehyde group, and is therefore an aldohexose. The glucose molecule can exist in an open-chain (acyclic) as well as ring (cyclic) form. Gluco ...
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Type II Diabetes
Type 2 diabetes, 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, and unexplained weight loss. Symptoms may also include increased hunger, feeling tired, and sores that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon. Type 2 diabetes primarily occurs as a result of obesity and lack of exercise. Some people are genetically more at risk than others. Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primarily to type 1 diabetes and gestational diabetes. In type 1 diabete ...
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Ketoacidosis
Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. While ketosis refers to any elevation of blood ketones, ketoacidosis is a specific pathologic condition that results in changes in blood pH and requires medical attention. The most common cause of ketoacidosis is diabetic ketoacidosis but can also be caused by alcohol, medications, toxins, and rarely, starvation. Signs and symptoms The symptoms of ketoacidosis are variable depending on the underlying cause. The most common symptoms include nausea, vomiting, abdominal pain, and weakness. Breath may also develop the smell of acetone as it is a volatile ketone that can be exhaled. Rapid deep breathing, or Kussmaul breathing, may be present to compensate for the metabolic acidosis. Altered mental status is more common in diabetic than alcoholic ketoacidosis. Causes Ketoacidosis is caused by the uncontrolled production of ketone bodies. Usually the production of keton ...
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Renal Glycosuria
Renal glycosuria is a rare condition in which the simple sugar glucose is excreted in the urine despite normal or low blood glucose levels. With normal kidney (renal) function, glucose is excreted in the urine only when there are abnormally elevated levels of glucose in the blood. However, in those with renal glycosuria, glucose is abnormally elevated in the urine due to improper functioning of the renal tubules, which are primary components of nephrons, the filtering units of the kidneys. Signs and symptoms In most affected individuals, the condition causes no apparent symptoms (asymptomatic) or serious effects. When renal glycosuria occurs as an isolated finding with otherwise normal kidney function, the condition is thought to be inherited as an autosomal recessive trait. Genetics It is associated with SLC5A2, coding the sodium-glucose cotransporter 2. Diagnosis A doctor normally can diagnose renal glycosuria when a routine urine test (Urinalysis) detects glucose in the uri ...
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Sodium/glucose Cotransporter 1
Sodium/glucose cotransporter 1 (SGLT1) also known as solute carrier family 5 member 1 is a protein in humans that is encoded by the gene which encodes the production of the SGLT1 protein to line the absorptive cells in the small intestine and the epithelial cells of the kidney tubules of the nephron for the purpose of glucose uptake into cells. Through the use of the sodium glucose cotransporter 1 protein, cells are able to obtain glucose which is further utilized to make and store energy for the cell. Structure The sodium glucose cotransporter 1 is classified as an integral membrane protein that is made up of 14 alpha-helices constructed from the folding of 482-718 amino acid residues with both the N and C-terminal residing upon the extracellular side of the plasma membrane. It is hypothesized that the protein contains protein kinase A and protein kinase C phosphorylation sites, which serve to regulate the proteins conformational shape through phosphorylation of amino acids w ...
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Diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased appetite. If left untreated, diabetes can cause many health complications. Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death. Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, damage to the nerves, damage to the eyes, and cognitive impairment. Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced. Insulin is a hormone which is responsible for helping glucose from food get into cells to be used for energy. There are three main types of diabetes mellitus: * Type 1 diabetes results from failure of the pancreas to produce enough insulin due to lo ...
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Homozygote
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Most eukaryotes have two matching sets of chromosomes; that is, they are diploid. Diploid organisms have the same loci on each of their two sets of homologous chromosomes except that the sequences at these loci may differ between the two chromosomes in a matching pair and that a few chromosomes may be mismatched as part of a chromosomal sex-determination system. If both alleles of a diploid organism are the same, the organism is homozygous at that locus. If they are different, the organism is heterozygous at that locus. If one allele is missing, it is hemizygous, and, if both alleles are missing, it is nullizygous. The DNA sequence of a gene often varies from one individual to another. These gene variants are called alleles. While some gen ...
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Open Field (animal Test)
Developed by Calvin S. Hall, the open field test is an experimental test used to assay general locomotor activity levels, anxiety, and willingness to explore in animals (usually rodents) in scientific research. However, the extent to which behavior in the open field measures anxiety is controversial. The open field test can be used to assess memory by evaluating the ability of the animal to recognize a stimuli or object. Another animal test that is used to assess memory using that same concept is the novel object recognition test. Concept Animals such as rats and mice display a natural aversion to brightly lit open areas. However, they also have a drive to explore a perceived threatening stimulus. Decreased levels of anxiety lead to increased exploratory behavior. Increased anxiety will result in less locomotion and a preference to stay close to the walls of the field (thigmotaxis). Experimental design The open field is an arena with walls to prevent escape. Commonly, the field ...
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Hot Plate Test
The hot plate test is a test of the pain response in animals, similar to the tail flick test. Both hot plate and tail-flick methods are used generally for centrally acting analgesic, while peripherally acting drugs are ineffective in these tests but sensitive to acetic acid-induced writhing test. The hot plate test is used in basic pain research and in testing the effectiveness of analgesics by observing the reaction to pain caused by heat. It was proposed by Eddy and Leimbach in 1953. They used a behavioral model of nociception where behaviors such as jumping and hind paw-licking are elicited following a noxious thermal stimulus. Licking is a rapid response to painful thermal stimuli that is a direct indicator of nociceptive threshold. Jumping represents a more elaborated response, with a latency, and encompasses an emotional component of escaping. Procedure * A transparent glass cylinder is used to keep the animal on the heated surface of the plate. * The temperature of the ho ...
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