The sodium/glucose cotransporter 2 (SGLT2) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the (solute carrier family 5 (sodium/glucose cotransporter))

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

SGLT2 is a member of the sodium glucose cotransporter family, which are sodium-dependent

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

transport proteins. SGLT2 is the major cotransporter involved in glucose

reabsorption In renal physiology, reabsorption, more specifically tubular reabsorption, is the process by which the nephron removes water and solutes from the tubular fluid (pre-urine) and returns them to the circulating blood. It is called ''reabsorption' ...

in the kidney. SGLT2 is located in the early

proximal tubule The proximal tubule is the segment of the nephron in kidneys which begins from the renal (tubular) pole of the Bowman's capsule to the beginning of loop of Henle. At this location, the glomerular parietal epithelial cells (PECs) lining bowman’s ...

, and is responsible for reabsorption of 80-90% of the glucose filtered by the kidney

glomerulus ''Glomerulus'' (; : glomeruli) is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to ...

. 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 inhibitor SGLT2 inhibitors (also called gliflozins or flozins) are a class of medications that inhibit sodium-glucose transport proteins in the nephron (the functional units of the kidney), unlike SGLT1, SGLT1 inhibitors that perform a similar function in ...

s are also called gliflozins or flozins. They lead to a reduction in blood glucose levels, and therefore have potential use in the treatment of

type 2 diabetes Type 2 diabetes (T2D), 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 ...

. Gliflozins enhance glycemic control as well as reduce

body weight Human body weight is a person's mass or weight. Strictly speaking, body weight is the measurement of mass without items located on the person. Practically though, body weight may be measured with clothes on, but without shoes or heavy accessori ...

and systolic and diastolic

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

. The gliflozins

canagliflozin Canagliflozin, sold under the brand name Invokana among others, is a medication used to treat type 2 diabetes. It is used together with exercise and diet. It is not recommended in type 1 diabetes. It is taken by mouth. Common side effects in ...

dapagliflozin Dapagliflozin, sold under the brand names Farxiga (US) and Forxiga (EU) among others, is a medication used to treat type2 diabetes. It is also used to treat adults with heart failure and chronic kidney disease. It reversibly inhibits sodium- ...

, and

empagliflozin Empagliflozin, sold under the brand name Jardiance ( ), among others, is an antidiabetic medication used to improve glucose control in people with type2 diabetes and/or for patients with established heart failure with reduced ejection fract ...

may lead to euglycemic

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 i ...

. Other side effects of gliflozins include increased risk of Fournier gangrene and of (generally mild) genital infections such as

candidal vulvovaginitis Vaginal yeast infection, also known as candidal vulvovaginitis and vaginal thrush, is excessive growth of yeast in the vagina that results in irritation. The most common symptom is vaginal itching, which may be severe. Other symptoms include burn ...

Clinical significance

Mutations in this gene are also associated with

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 elevat ...

. Sodium-glucose cotransporter-2 (SGLT2) inhibitors were associated with significant long-term reductions in mortality risk for patients with pulmonary arterial hypertension (PAH), according to an observational cohort study. The study revealed that after one year, 8.1% of PAH patients prescribed SGLT2 inhibitors had died, compared to 15.5% of those who did not take the medication.

Function

SGLT2 inhibitors for diabetes

Clinical significance

See also

References

Further reading