This is a working overview of incretin, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-04-23. Anything still debated is marked as such rather than presented as settled.
Receptor activation follows the canonical Gs pathway: binding increases intracellular cyclic AMP, which promotes protein kinase A activity. In pancreatic beta cells this amplifies glucose-dependent insulin release, so secretion rises when blood glucose is high and changes little when it is low. The same signalling suppresses glucagon release from alpha cells and slows gastric emptying. Receptors in the hypothalamus and brainstem are thought to contribute to reduced appetite and lower energy intake. Which of these effects dominates clinical outcomes remains an area of active study.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released by intestinal L cells after food intake. The natural hormone acts on pancreatic and central receptors but is degraded within minutes by dipeptidyl peptidase-4 and other peptidases. Semaglutide belongs to the class of long-acting GLP-1 receptor agonists, a group distinguished by structural changes that slow breakdown and extend circulation time. Its development followed earlier short-acting analogues and reflects a general strategy in peptide drug design: preserve receptor activity while blocking proteolytic clearance.
Three structural changes define the molecule. At position 8 an alpha-aminoisobutyric acid residue replaces alanine, which blocks dipeptidyl peptidase-4 cleavage. At position 34 arginine replaces lysine, and at position 26 a lysine carries a C18 fatty diacid attached through a short linker. The fatty chain binds serum albumin, and this albumin association reduces renal filtration and enzymatic attack. The unchanged backbone retains the receptor contacts that produce signalling. The free base has the formula C187H291N45O59 and a molecular weight near 4114 daltons.
Receptor binding triggers G protein signaling that raises intracellular cyclic AMP in pancreatic beta cells. Insulin release follows in a glucose-dependent manner, so secretion increases when blood glucose is elevated and diminishes when it is not. The same signaling suppresses glucagon release from alpha cells and slows gastric emptying, which blunts the post-meal glucose rise. In the brain, receptor activation in regions such as the arcuate nucleus is associated with reduced appetite and lower energy intake. How much each of these effects contributes to overall weight change is not fully settled.
Two structural features account for the prolonged half-life of semaglutide. A modified amino acid at position 8 resists cleavage by dipeptidyl peptidase-4, the enzyme that rapidly degrades native GLP-1. A fatty diacid side chain binds serum albumin, which limits renal clearance and protects the peptide from enzymatic breakdown. These modifications yield a plasma half-life of approximately one week in humans, allowing once-weekly administration. The relationship between plasma concentration and clinical effect varies between individuals, and sources of that variability are still being characterized.
Semaglutide is a synthetic peptide analog of glucagon-like peptide-1 (GLP-1), a hormone released from intestinal L-cells after food intake. The compound belongs to the incretin mimetic class and acts at GLP-1 receptors distributed across pancreatic, gastrointestinal, cardiovascular, and central nervous system tissues. Compared with native GLP-1, the molecule carries structural changes that extend its activity from minutes to roughly one week. It is studied for glycemic control in type 2 diabetes and for weight management, and its effects on cardiovascular and other outcomes remain active research areas.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C187H291N45O59 | free base, without counter-ion |
| Molecular weight | About 4114 Da | peptide backbone plus attached lipid chain |
| Plasma half-life | About 165 hours | supports once-weekly dosing in humans |
| Plasma protein binding | Greater than 99 percent | attributed mainly to serum albumin |
| Receptor target | GLP-1 receptor | Gs-coupled, raises intracellular cyclic AMP |
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.
Activation of the GLP-1 receptor couples to Gs signalling and raises intracellular cyclic AMP in pancreatic beta cells. The resulting insulin release depends on prevailing glucose concentrations, so the effect is greater when glucose is elevated. Receptor engagement also suppresses glucagon secretion and slows gastric emptying, which flattens post-meal glucose excursions. In the central nervous system, signalling in hypothalamic and brainstem regions is associated with reduced appetite and lower energy intake. Studies continue to examine effects on cardiac, renal and hepatic endpoints; whether those benefits are independent of weight change remains an open question.
Clinical development of this compound followed earlier short-acting GLP-1 analogues that required frequent injection. Once-weekly subcutaneous formulations entered use after 2017, and an oral formulation using a permeation enhancer later became available. The oral version pairs the peptide with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, a carrier that improves uptake across the gastric epithelium. Interest has expanded from glycaemic control into weight management and metabolic liver disease. Regulatory status and approved indications differ between countries, and the product remains subject to ongoing safety monitoring.
Semaglutide is a synthetic peptide that acts as an agonist at the glucagon-like peptide-1 receptor. It is a structural analogue of human GLP-1(7-37), modified to resist enzymatic degradation by dipeptidyl peptidase-4. The peptide backbone contains alpha-aminoisobutyric acid at position 8, a substitution that stabilises the helix and slows cleavage. A fatty diacid side chain attached through a linker at lysine 34 promotes binding to serum albumin, which extends the circulating half-life. These two modifications together allow less frequent administration than native GLP-1 requires.
皮下注射后吸收相对缓慢，绝对生物利用度约为百分之八十九，血药浓度峰值通常出现在给药后一到三天。与白蛋白结合使清除减慢，终末半衰期约为一百六十五小时，接近一周。连续给药约四到五周后达到稳态暴露水平。表观分布容积约为每千克零点二五升，血浆蛋白结合率超过百分之九十九。代谢以蛋白水解切割和脂肪二酸侧链的 β-氧化为主，相关产物主要经尿液与粪便排出。
序列层面的改动同时解决了两个问题，即酶解稳定性与肾脏清除速度。天然 GLP-1 在循环中的半衰期仅约两分钟，主要被二肽基肽酶-4 迅速灭活。酰化侧链与白蛋白的可逆结合形成循环储库，使分子缓慢释放并持续激活受体。这种设计思路后来被广泛用于同类长效肽的开发，属于该类药物化学改造的典型范式。
Semaglutide 是一种经结构修饰的胰高血糖素样肽-1 类似物，其主链与内源性 GLP-1(7-36) 约有百分之九十四的序列一致性。第 8 位丙氨酸被 α-氨基异丁酸取代，使二肽基肽酶-4 无法识别原有切割位点。第 34 位赖氨酸换为精氨酸，进一步降低酶解速率。第 26 位赖氨酸经间隔基连接一条含十八个碳的二酸脂肪链，该侧链赋予分子与血浆白蛋白结合的能力。
Semaglutide dissolves readily in water and in aqueous buffers near neutral pH. Solubility decreases near the isoelectric point, where net charge is minimal. Common laboratory solvents include phosphate-buffered saline and dilute ammonium bicarbonate. Strongly acidic or basic conditions may accelerate hydrolysis. Working concentrations are usually prepared by diluting a concentrated stock. Vial surfaces can adsorb small amounts of peptide at low concentrations, so carrier proteins or low-binding tubes are sometimes used.
Reverse-phase high-performance liquid chromatography is the standard method for purity assessment, separating the peptide from truncated or oxidized variants. Mass spectrometry confirms molecular mass and detects modifications, while ultraviolet absorbance near 280 nanometers supports concentration measurement through tryptophan and tyrosine residues. Circular dichroism can indicate secondary structure, though the peptide is largely helical in solution, and ion-exchange chromatography resolves charge variants. Purity values above 95 percent are typical for research-grade material. Stability studies track degradation over time under defined conditions.
=== 11 May === The Ukrainian army said that they had broken through advancing Russian formations northwest of Bakhmut. Geolocated footage showed Ukrainian troops counterattacking near Khromove and Bila Hora, which Russian forces were trying to seize in order to encircle the city. Ukrainian sources said their forces advanced 2.6 km (1.6 mi) along a 3 km-wide (1.9-mile) front, destroying the 6th and 8th companies of the Russian 72nd Separate Motor Rifle Brigade; the head of the Wagner Group, Yevgeny Prigozhin, said already on 9 May that Russian troops had abandoned some positions on his flank in Bakhmut. The claim was also shared by Russian military bloggers but denied by the Russian Defence Ministry, which said that Russian forces repelled a surge of Ukrainian attacks in Soledar and that its forces had fallen back to "more favourable positions" near the Berkhivka reservoir northwest of Bakhmut for tactical reasons. The United Kingdom Secretary for Defence Ben Wallace announced that the UK supplied Ukraine with Storm Shadow missiles. With a range of 250 kilometres, the missiles are capable of hitting targets in Crimea from the positions currently held by Ukraine. The United States supported the UK's decision.
== Generation of endocrine progenitor cells from pancreatic islets == Similar to generation of Cancer Stem Cells, EMT was demonstrated to generate endocrine progenitor cells from human pancreatic islets. Initially, the human islet-derived progenitor cells (hIPCs) were proposed to be better precursors since β-cell progeny in these hIPCs inherit epigenetic marks that define an active insulin promoter region. However, later, another set of experiments suggested that labelled β-cells de-differentiate to a mesenchymal-like phenotype in vitro, but fail to proliferate; thus initiating a debate in 2007. Since these studies in human islets lacked lineage-tracing analysis, these findings from irreversibly tagged beta cells in mice were extrapolated to human islets. Thus, using a dual lentiviral and genetic lineage tracing system to label β-cells, it was convincingly demonstrated that adult human islet β-cells undergo EMT and proliferate in vitro. Also, these findings were confirmed in human fetal pancreatic insulin-producing cells, and the mesenchymal cells derived from pancreatic islets can undergo the reverse of EMT – MET – to generate islet-like cell aggregates. Thus, the concept of generating progenitors from insulin-producing cells by EMT or generation of Cancer Stem Cells during EMT in cancer may have potential for replacement therapy in diabetes, and call for drugs targeting inhibition of EMT in cancer.
=== Cancer === Sugar consumption does not directly cause cancer. Cancer Council Australia have stated that "there is no evidence that consuming sugar makes cancer cells grow faster or cause cancer". There is an indirect relationship between sugar consumption and obesity-related cancers through increased risk of excess body weight. The American Institute for Cancer Research and World Cancer Research Fund recommend that people should limit sugar consumption.
Below 5 °C (41 °F), the honey will not crystallize, thus the original texture and flavor can be preserved indefinitely. Honey is a supercooled liquid when stored below its melting point, as is normal. At very low temperatures, honey does not freeze solid; rather its viscosity increases. Like most viscous liquids, the honey becomes thick and sluggish with decreasing temperature. At −20 °C (−4 °F), honey may appear or even feel solid, but it continues to flow at very low rates. Honey has a glass transition between −42 and −51 °C (−44 and −60 °F). Below this temperature, honey enters a glassy state and becomes an amorphous solid (noncrystalline).
Sources: en.wikipedia.org
GABAA receptor: positive allosteric modulator (primarily of δ subunit-containing receptors) NMDA receptor: negative allosteric modulator AMPA receptor: negative allosteric modulator Kainate receptor: negative allosteric modulator Glycine receptor: positive allosteric modulator Serotonin 5-HT3 receptor: positive allosteric modulator Opioid receptor: endogenous positive allosteric modulator Muscarinic acetylcholine receptor: positive allosteric modulator. Nicotinic acetylcholine receptor: positive allosteric modulator Glycine reuptake inhibitor Adenosine reuptake inhibitor L-type calcium channel: channel blocker GIRK: channel opener Voltage-gated calcium channel Dihydropyridine-sensitive L-type Ca2+ channels BK channel modulation G-protein-activated inwardly rectifying K+ channels Brain medulla: Decreased levels of nitric oxide Mesolimbic pathway: Increased levels of dopamine and endogenous opioids, secondary to other actions Many of these actions have been found to occur only at very high concentrations that may not be pharmacologically significant at recreational doses of ethanol, and it is unclear how or to what extent each of the individual actions is involved in the effects of ethanol. Some of the actions of ethanol on ligand-gated ion channels, specifically the nicotinic acetylcholine receptors and the glycine receptor, are dose-dependent, with potentiation or inhibition occurring dependent on ethanol concentration. This seems to be because the effects of ethanol on these channels are a summation of positive and negative allosteric modulatory actions.
Radical materials advances can drive the creation of new products or even new industries, but stable industries also employ materials scientists to make incremental improvements and troubleshoot issues with currently used materials. Industrial applications of materials science include materials design, cost-benefit tradeoffs in industrial production of materials, processing methods (casting, rolling, welding, ion implantation, crystal growth, thin-film deposition, sintering, glassblowing, etc.), and analytic methods (characterization methods such as electron microscopy, X-ray diffraction, calorimetry, nuclear microscopy (HEFIB), Rutherford backscattering, neutron diffraction, small-angle X-ray scattering (SAXS), etc.). Besides material characterization, the material scientist or engineer also deals with extracting materials and converting them into useful forms. Thus ingot casting, foundry methods, blast furnace extraction, and electrolytic extraction are all part of the required knowledge of a materials engineer. Often the presence, absence, or variation of minute quantities of secondary elements and compounds in a bulk material will greatly affect the final properties of the materials produced. For example, steels are classified based on 1/10 and 1/100 weight percentages of the carbon and other alloying elements they contain. Thus, the extracting and purifying methods used to extract iron in a blast furnace can affect the quality of steel that is produced. Solid materials are generally grouped into three basic classifications: ceramics, metals, and polymers.
=== Lesions === The majority of vocal fold lesions primarily arise in the cover of the folds. Since the basal lamina secures the epithelium to the superficial layer of the lamina propria with anchoring fibers, this is a common site for injury. If a person has a phonotrauma or habitual vocal hyperfunction, also known as pressed phonation, the proteins in the basal lamina can shear, causing vocal fold injury, usually seen as nodules or polyps, which increase the mass and thickness of the cover. The squamous cell epithelium of the anterior glottis are also a frequent site of laryngeal cancer caused by smoking.
Sources: en.wikipedia.org
These fractions also contained toxins readily separable from the short-chain isotoxin by preparative reverse-phase chromatography. Amino-acid sequencing of the first 28 residues indicated that both toxins were long-chain neurotoxins with identical N-termini. The LD50 of long-chain neurotoxins 2 from N. a. annulata and N. christyi venoms were 0.086 and 0.090 mg/kg, respectively. The venoms of these little-known elapids have some of the lowest intraperitoneal LD50 values of any African Naja species studied thus far, and have high concentrations of potent postsynaptic neurotoxins.
== V == vaccine – vacuole – varicella-zoster virus – vascular cambium – vascular tissue – vein – vertebrate – vesicle – vesicular stomatitis virus – vestibular system – vicariance – virology – viral classification – virus – viral evolution – viridamide – visible light – vision – vitamin - Viroid
3,4-Dimethoxyamphetamine (3,4-DMA), or simply dimethoxyamphetamine (DMA), is a psychedelic drug of the phenethylamine and amphetamine families. It is one of the dimethoxyamphetamine (DMA) series of positional isomers. The drug is also an analogue of other psychedelics like 3,4-methylenedioxyamphetamine (MDA), 3,4,5-trimethoxyamphetamine (TMA), and mescaline (3,4,5-trimethoxyphenethylamine). It has been reported to produce psychedelic effects in humans but only entactogen-like effects without stimulant- or psychedelic-like effects in animals.
==== Advantages ==== The biggest advantage of GFP is that it can be heritable, depending on how it was introduced, allowing for continued study of cells and tissues it is expressed in. Visualizing GFP is noninvasive, requiring only illumination with blue light. GFP alone does not interfere with biological processes, but when fused to proteins of interest, careful design of linkers is required to maintain the function of the protein of interest. Moreover, if used with a monomer it is able to diffuse readily throughout cells.
Sources: en.wikipedia.org
Native GLP-1 is a short-lived peptide cleared within one to two minutes by dipeptidyl peptidase-4 and related enzymes. Semaglutide keeps the receptor-binding backbone but adds substitutions and a lipid chain. These changes block the main cleavage site and allow reversible albumin binding, extending the half-life to roughly 165 hours.
Albumin is the most abundant protein in plasma and carries molecules that bear fatty-acid chains. Binding shields the peptide from renal filtration and from peptidases, keeping a circulating reservoir. Slow release from this reservoir produces sustained receptor occupancy and supports infrequent dosing.
The insulinotropic effect is glucose-dependent, meaning secretion increases mainly when glucose is elevated. This property is often described as lowering the chance of hypoglycaemia when the compound is used alone. Other glucose-lowering agents used at the same time can still cause low blood glucose.
Native GLP-1 is degraded within minutes by dipeptidyl peptidase-4 and cleared quickly. Semaglutide carries a position 8 substitution that blocks that cleavage and a fatty diacid chain that binds albumin. Together these changes extend its circulating half-life to about one week.