The short version of incretin fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2025-12-18 and is reviewed periodically as new material appears.
The company that developed the compound filed it as a long-acting analogue, and it gained first approval in 2017 for type 2 diabetes. Later authorisations from several regulators extended the indication to chronic weight management, and the World Health Organization added the glucagon-like peptide-1 receptor agonist drug class to its model list of essential medicines in 2023. Production uses solid-phase peptide synthesis followed by side-chain conjugation and chromatographic purification. Supply constraints and cost differences across regions are well documented. Literature on long-term outcomes continues to grow, with many trials reporting surrogate endpoints rather than hard clinical endpoints.
Semaglutide is a synthetic peptide of thirty-one amino acids that shares roughly ninety-four percent sequence identity with human glucagon-like peptide-1. Two substitutions resist enzymatic cleavage by dipeptidyl peptidase-4, and a fatty diacid side chain attached through a linker promotes binding to serum albumin. That albumin binding slows renal clearance and extends the circulating half-life from minutes to approximately one week. The structural changes are well established in the published literature. Whether the same modifications affect receptor signalling bias in ways that matter clinically remains an open question.
Pharmacological activity arises from agonism at the glucagon-like peptide-1 receptor, a G protein-coupled receptor expressed in the pancreas, the gastrointestinal tract, and the brainstem. Receptor activation raises intracellular cyclic adenosine monophosphate and enhances insulin release in a glucose-dependent manner, an effect that diminishes when blood glucose concentration is low. Other effects include slowed gastric emptying and hypothalamic satiety signalling. These pathways are described well. Receptor desensitisation rates across tissues, relative to the endogenous hormone, are still under investigation, and reported findings differ between laboratories.
Stability studies examine how temperature, pH, and moisture influence degradation rates over time. In aqueous solution, hydrolysis and deamidation accelerate as pH moves away from mildly acidic conditions. Light exposure and residual metal ions can also trigger oxidation of susceptible residues. Accelerated aging at elevated temperature is used to estimate shelf life, though extrapolation to room temperature carries uncertainty because individual degradation pathways do not always scale predictably.
Lyophilized semaglutide powder is typically held at minus twenty degrees Celsius for long-term storage. At that temperature, solid-state degradation reactions proceed slowly and the peptide remains intact for extended periods. Repeated freeze-thaw cycles are best avoided because they promote aggregation and can shift the proportion of monomeric peptide present. Working aliquots are often prepared so that each portion is thawed only once, and desiccant is placed inside the vial to limit moisture uptake.
| Property | Value | Notes |
|---|---|---|
| Molecular class | 31-amino-acid peptide | Modified glucagon-like peptide-1 analogue |
| Molecular mass | approximately 4114 Da | Calculated for the free peptide backbone |
| Appearance | white to off-white powder | Typical of purified lyophilised peptide batches |
| Solubility class | freely soluble in water | Aqueous solubility improves at slightly alkaline pH |
| Typical storage | -20 degrees Celsius, dry, dark | Protect from repeated freeze-thaw cycles |
Semaglutide belongs to the glucagon-like peptide-1 receptor agonist class, a group of synthetic peptides that imitate an incretin hormone released by intestinal L cells after food intake. Native GLP-1 circulates for only a few minutes because dipeptidyl peptidase-4 cleaves it rapidly. The hormone acts on pancreatic islets, the gastrointestinal tract, and several brain regions. Because the natural peptide is short-lived, development work concentrated on analogues that keep receptor activity while resisting enzymatic breakdown and renal clearance.
The semaglutide sequence is a 31-residue analogue of human GLP-1, altered at three positions relative to the parent hormone. Aminoisobutyric acid replaces alanine at position 8, arginine replaces lysine at position 34, and a lipophilic diacid is attached to lysine 26 through a short linker. These features are reported consistently in the structural literature. The position 8 substitution blocks recognition by dipeptidyl peptidase-4, while the attached chain drives strong, reversible association with a carrier protein in blood.
Receptor activation raises intracellular cyclic AMP through Gs coupling, which promotes glucose-dependent insulin release and suppresses glucagon secretion when blood glucose is elevated. Effects outside the pancreas include slower gastric emptying and altered appetite signalling in the hypothalamus and hindbrain. The relative contribution of each tissue to overall metabolic outcomes remains an area of active investigation. Central mechanisms in particular are inferred mainly from animal models and indirect human measures rather than direct observation.
The primary target is the GLP-1 receptor, a class B G protein-coupled receptor expressed on pancreatic beta cells, in the gut, and in several brain regions. Receptor activation raises intracellular cyclic AMP, which potentiates glucose-dependent insulin secretion and lowers glucagon release when blood glucose is elevated. Signalling in the hypothalamus and brainstem is associated with reduced appetite and slower gastric emptying. Because the insulinotropic effect depends on prevailing glucose levels, the hypoglycaemic risk of the peptide alone is described as low in most study settings. The relative contribution of peripheral and central actions remains an active research question.
Large randomised trials in adults with type 2 diabetes and in adults with obesity have reported reductions in body weight and improvements in several cardiovascular risk markers. One outcome trial found a lower incidence of major adverse cardiovascular events in participants with diabetes and established cardiovascular disease. Gastrointestinal effects such as nausea and vomiting are the most frequently reported adverse events and often diminish over time. Changes in lean body mass during weight loss are an area of ongoing investigation. Effects in adolescents and in pregnancy are less well characterised, and current labelling advises against use during pregnancy.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released after nutrient intake. The molecule contains 31 amino acid residues and differs from the native sequence at several positions. A non-natural residue at position eight resists the enzyme that normally truncates the hormone, while a lysine-linked fatty diacid side chain promotes binding to serum albumin. These two modifications extend the circulating half-life from minutes to roughly one week. The peptide is produced by solid-phase synthesis followed by selective acylation, and its identity and purity are confirmed by spectrometric and chromatographic techniques.
== Early life and education == Sangeeta Bhatia was born in 1968 in Boston, Massachusetts, to parents who emigrated from India. She is an alumna of Lexington High School in Lexington, MA. Her father was an engineer and entrepreneur, and her mother was one of the first women to receive an MBA in India. Bhatia's interest in engineering was sparked during her 10th-grade biology class and a visit with her father to an MIT lab, where she witnessed a demonstration of an ultrasound machine for cancer treatment. She pursued bioengineering at Brown University, where her involvement in a research group studying artificial organs solidified her decision to pursue graduate studies in the field. After graduating with honors in 1990, Bhatia was initially rejected from the MD-PhD program run by the Harvard-MIT Division of Health Sciences and Technology (HST) but was accepted into the Mechanical Engineering Master's program. She was subsequently accepted into the HST MD-PhD program, where she was advised by Mehmet Toner. She received her Ph.D. in 1997 and her M.D. in 1999, followed by postdoctoral training at Massachusetts General Hospital. Bhatia met her husband, Jagesh Shah, as classmates in HST. Shah is currently an executive in the biotechnology industry. They have two daughters.
Later on, his statements about doping in the Bundesliga were supported by Per Roentved, Hans Werner Moors, Dieter Schatzscheider, Hans-Josef Kapellmann, Peter Neururer, Benno Möhlmann, Uwe Nester, Peter Geyer (who talked about procedure, quantity and side effects), Jürgen Röber, Jürgen Stumm and Peter Harms (both medics). At Olympique Marseille, doping took place according to Marcel Desailly, Jean-Jacques Eydelie, Chris Waddle, and Tony Cascarino. They told about stimulants taken prior to their big games, which made them more energetic and keen. According to Eydelie, "all [of them] took a series of injections" in the 1993 Champions League final, except Rudi Völler. All this was no surprise for Arsene Wenger, who said everyone in France assumed something like that going on. Additionally, Desailly and Cascarino claimed that Bernard Tapie, the president himself, distributed pills and injections. Author Mondenard also mentioned "injections for everyone". Tapie only admitted that some players took Captagon. Although Juventus won the 1996 Champions League final, the victory was overshowed by of accusations of doping. The Juventus team has been accused of using erythropoietin (EPO) and the matter went to trial in 2004.
=== Attention-deficit hyperactivity disorder === One in four people who have a substance use disorder also have attention-deficit hyperactivity disorder, which makes the treatment of both conditions more difficult. ADHD is associated with an increased craving for drugs. Having ADHD makes it more likely that an individual will initiate substance misuse at a younger age than their peers. They are also more likely to experience poorer outcomes, such as longer time to remission, and to have increased psychiatric complications from substance misuse. While generally stimulant medications do not seem to worsen substance use, they are known to be non-medically used in some cases. Psychosocial therapy and/or nonstimulant medications and extended release stimulants are ADHD treatment options that reduce these risks.
Vicryl (polyglactin 910) is an absorbable, synthetic, usually braided suture, manufactured by Ethicon Inc., a subsidiary of Johnson and Johnson. A monofilament version is also made for use in ophthalmic practice. It is indicated for soft tissue approximation and ligation. The suture holds its tensile strength for approximately two to three weeks in tissue and is completely absorbed by acid hydrolysis within 8-10 weeks. Vicryl and other polyglycolic-acid sutures may also be treated for more rapid breakdown ("Vicryl Rapide") in rapidly healing tissues such as mucous membrane or impregnated with triclosan ("Vicryl Plus Antibacterial") to provide antimicrobial protection of the suture line. Because Vicryl is slow-absorbing and often braided, its use is contraindicated in the closure of any cutaneous wound exposed to the air, as it draws moisture from the healing tissue to the skin and allows bacteria and irritants to migrate into the wound. This may lead to high reactivity to the contaminants, poor wound healing, and eventually infection. Although the name "Vicryl" is a trademark of Ethicon, the term "vicryl" has been used generically referring to any synthetic absorbable suture made primarily of polyglycolic acid. Other brands of polyglycolic acid suture include PolySyn, Surgicryl, Polysorb, and Dexon, all of which are manufactured by different companies. Vicryl is a copolymer of lactide (a bislactone of lactic acid) and glycolide (a bislactone of glycolic acid).
As a concession made by Lamartine to popular aspirations, and in exchange for the maintaining of the tricolor flag, he conceded the Republican triptych of Liberté, Égalité, Fraternité, written on the flag, on which a red rosette was also to be added. The first collision took place as to the form which the 1848 Revolution was to take. Lamartine wished for them to maintain their original principles, with the whole country as supreme, whereas the revolutionaries under Ledru-Rollin wished for the Republic of Paris to hold a monopoly on political power. On 5 March the government, under the pressure of the Parisian clubs, decided in favor of an immediate reference to the people, and direct universal suffrage, and adjourned it until 26 April. This added the uneducated masses to the electorate and led to the election of the Constituent Assembly on 4 May 1848. The provisional government having resigned, the republican and anti-socialist majority on 9 May entrusted the supreme power to an Executive Commission consisting of five members: Arago, Pierre Marie de Saint-Georges, Garnier-Pagès, Lamartine, and Ledru-Rollin. The result of the general election, the return of a predominantly moderate, if not monarchical, constituent assembly dashed the hopes of those who had looked for the establishment, by a peaceful revolution, of their ideal socialist state. but they were not prepared to yield without a struggle, and in Paris itself they commanded a formidable force.
Sources: en.wikipedia.org
If areas were depopulated of Neanderthals as a consequence of climate change (specifically Heinrich event 4) or a natural disaster (the Campanian Ignimbrite eruption), Neanderthals may not have been as fast as modern humans in recolonising.
Although Ginkgo biloba and other species of the genus were once widespread throughout the world, its habitat had shrunk by two million years ago. For centuries, it was thought to be extinct in the wild, but is now a common tree cultivated throughout eastern China, Korea, and Japan. Many municipalities in China, Korea and Japan use ginkgos as street trees, and ginkgo leaves are the emblem of prominent educational institutions such as the University of Tokyo and Sungkyunkwan University in South Korea. Despite their widespread habitat, high genetic uniformity exists among ginkgo trees, with some Chinese scholars suggesting that ginkgo trees in these areas may have been planted and preserved by Chinese monks over about 1,000 years. A study demonstrates a greater genetic diversity in Southwestern China populations, supporting glacial refugia in mountains surrounding the eastern Tibetan Plateau, where several old-growth candidates for wild populations have been reported. Whether native ginkgo populations still exist has not been demonstrated unequivocally, but there is genetic evidence that these Southwestern populations may be wild, as well as evidence that the largest and oldest G. biloba trees may be older than surrounding human settlements. Where it occurs in the wild, Ginkgo is found infrequently in deciduous forests and valleys on acidic loess (i.e. fine, silty soil) with good drainage. The soil it inhabits is typically in the pH range of 5.0 to 5.5.
==== Structural ==== Structural metamaterials are a type of mechanical metamaterial that provide properties such as crushability and lightweight characteristics. Using projection micro-stereolithography, microlattices can be created using forms much like trusses and girders. Materials four orders of magnitude stiffer than conventional aerogel, but with the same density have been created. Such materials can withstand a load of at least 160,000 times their own weight by over-constraining the materials. A ceramic nanotruss metamaterial can be flattened and revert to its original state. While metamaterials derive their properties from engineered micro- or nano-scale architectures that manipulate wave behaviour, metastructures operate at the macro-scale, using geometric design and modular assembly to achieve multifunctional mechanical performance across larger systems. Fully bio-based composite and modular metastructure cells based on trussed geometry encompassing bamboo rods and plant-based polymer joints demonstrate scalable mechanical performance, supporting up to 700 kg in compression with a mass of 30 g.
=== 7 February === The SAF claimed to have retaken the Traffic Signs and License Plates Factory along with the entire industrial area of Khartoum. They also claimed to have retaken Al-Masoudiya in Khartoum state and Abu Quta in northwestern Gezira State. The SAF claimed to have shot down seven RSF drones over Debba, Northern State. Three people were killed in an RSF attack on the Zamzam IDP camp. Five others were killed in an RSF attack on Saloma, southeast of El Fasher.
== Causes of reduction == An increased number of red blood cells (polycythemia) causes reduced ESR as blood viscosity increases. Hemoglobinopathy such as sickle-cell disease can have low ESR due to an improper shape of red blood cells that impairs stacking.
Sources: en.wikipedia.org
=== Microcins === Microcins are all RiPPs produced by Enterobacteriaceae with a molecular weight <10 kDa. Many members of other RiPP families, such as microcin E492, microcin B17 (LAP) and microcin J25 (Lasso peptide) are also considered microcins. Instead of being classified based on posttranslational modifications or modifying enzymes, microcins are instead identified by molecular weight, native producer, and antibacterial activity. Microcins are either plasmid- or chromosome-encoded, but specifically have activity against Enerobacteriaceae. Because these organisms are also often producers of microcins, the gene cluster contains not only a precursor peptide and modification enzymes, but also a self-immunity gene to protect the producing strain, and genes encoding export of the natural product. Microcins have bioactivity against Gram-negative bacteria but usually display narrow-spectrum activity due to hijacking of specific receptors involved in the transport of essential nutrients.
serine + tetrahydrofolate → glycine + N5,N10-methylene tetrahydrofolate + H2O In E. coli, antibiotics that target folate depletes the supply of active tetrahydrofolates, halting glycine biosynthesis as a consequence. In the liver of vertebrates, glycine synthesis is catalyzed by glycine synthase (also called glycine cleavage enzyme). This conversion is readily reversible:
=== Use in the removal of phenolic compounds from wastewater === Researchers have found spongin to be useful in the photocatalytic degradation and removal of bisphenols (such as BPA) in wastewater. A heterogeneous catalyst consisting of a spongin scaffold for iron phthalocyanine (SFe) in conjunction with peroxide and UV radiation has been shown to remove phenolic wastes more quickly and efficiently than conventional methods. Other research using spongin scaffolds for the immobilization of Trametes versicolor Laccase has shown similar results in phenol degradation.
Several medications can help alleviate symptoms of EDS, such as pain and blood pressure drugs, which reduce joint pain and complications caused by blood vessel weakness. Some forms of EDS result in a normal life expectancy, but those that affect blood vessels generally decrease it. All forms of EDS can result in fatal outcomes for some patients. While EDS affects at least one in 5,000 people globally, other types occur at lower frequencies. The prognosis depends on the specific disorder. Excess mobility was first described by Hippocrates in 400 BC. The syndromes are named after two physicians, Edvard Ehlers and Henri-Alexandre Danlos, who described them at the turn of the 20th century.
Sources: en.wikipedia.org
It is a glucagon-like peptide-1 receptor agonist, often grouped with the incretin mimetics. Its backbone is modified from the human hormone to resist enzymatic degradation and to bind albumin. These two features distinguish it from the native peptide.
No. It shares high sequence identity but carries non-natural modifications that alter its stability and clearance. The naturally occurring hormone is broken down within minutes, while the synthetic analogue circulates far longer.
Attachment to serum albumin reduces renal filtration of the peptide and shields it from enzymatic breakdown. The consequence is a much longer interval between administrations than unmodified peptides allow. The precise contribution of binding affinity to overall duration is still being quantified.
Manufacturers commonly state multi-year stability when the powder is kept dry and frozen. Actual shelf life depends on residual moisture, vial sealing, and storage temperature. A re-test by chromatography is the only way to confirm remaining purity.