This is a working overview of GLP-1 receptor agonist, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-11-01. Anything still debated is marked as such rather than presented as settled.
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.
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.
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。
该分子作为 GLP-1 受体的选择性激动剂发挥作用，受体属于 B 类 G 蛋白偶联受体家族，激活后经 Gs 通路提升细胞内环腺苷酸水平。在胰腺 β 细胞，信号促进葡萄糖依赖性的胰岛素释放，血糖偏低时该作用明显减弱。在胰岛 α 细胞，胰高血糖素分泌受到抑制。中枢神经系统与胃肠道同样存在受体表达，相应信号参与食欲调节以及胃排空速率的降低。
| Property | Value | Notes |
|---|---|---|
| Molecular class | Acylated GLP-1 receptor agonist | 31-residue synthetic peptide |
| Molecular formula | C187H291N45O59 | established for the free peptide |
| Appearance | White to off-white powder | as supplied before formulation |
| Solubility | Freely soluble in water | aqueous buffers near neutral pH |
| Typical storage | 2 to 8 degrees Celsius, protected from light | powder and solution forms differ in shelf life |
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.
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.
Lyophilized semaglutide is typically stored at temperatures between minus 20 and minus 80 degrees Celsius for long-term preservation. Short-term storage at 2 to 8 degrees Celsius is common for working aliquots. Repeated freeze-thaw cycles can degrade the peptide and are usually avoided. The molecule is hygroscopic in its solid form, so containers should remain sealed with desiccant. Solutions are less stable than powders and are generally prepared fresh. Light exposure is limited because aromatic residues can undergo photo-oxidation.
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.
== Mechanism == Aspartate transaminase, as with all transaminases, operates via dual substrate recognition; that is, it is able to recognize and selectively bind two amino acids (Asp and Glu) with different side-chains. In either case, the transaminase reaction consists of two similar half-reactions that constitute what is referred to as a ping-pong mechanism. In the first half-reaction, amino acid 1 (e.g., L-Asp) reacts with the enzyme-PLP complex to generate ketoacid 1 (oxaloacetate) and the modified enzyme-PMP. In the second half-reaction, ketoacid 2 (α-ketoglutarate) reacts with enzyme-PMP to produce amino acid 2 (L-Glu), regenerating the original enzyme-PLP in the process. Formation of a racemic product (D-Glu) is very rare. The specific steps for the half-reaction of enzyme-PLP + aspartate
The series' first program War, Oil and Power was compiled and released in 1990, before the war broke out. News World Order was the title of another program in the series; it focused on the media's complicity in promoting the war, as well as Americans' reactions to the media coverage. Media watchdog group Fairness and Accuracy in Reporting (FAIR) critically analyzed media coverage during the war in various articles and books, such as the 1991 Gulf War Coverage: The Worst Censorship was at Home.
=== Male pheromones === d-linalool m-cresol p-cresol Although males engage in mate searching behavior more often than females, male cabbage loopers also produce pheromones from the hair pencils on the abdomen. Different blends of pheromones serve as competitive advantages for mating, as certain pheromone components are more appealing to females than others. Cresol is important for attractiveness to females, while linalool is found in floral odors and is believed to attract individuals searching for nutrients. Males around host plants are more attractive to females, because plant odor enhances the attractiveness of the male pheromone. This is advantageous to females because it helps with mate choice, as plant odor-enhanced males are more likely to be near a host plant. The male pheromone may also be related to food-finding behavior, as both males and females are more attracted to the male pheromone when starving. Although there is no direct evidence demonstrating that males release pheromones in response to host plant odor, it is highly possible this behavior occurs, and that the lack of evidence is due to either the choice of host plant or the experimental setup.
Sources: en.wikipedia.org
Eccles, Jessica A.; Cadar, Dorina; Quadt, Lisa; Hakim, Alan J.; Gall, Nicholas; Bowyer, Vicky; Cheetham, Nathan; Steves, Claire J.; Critchley, Hugo D.; Davies, Kevin A. (2024). "Is joint hypermobility linked to self-reported non-recovery from COVID-19? Case–control evidence from the British COVID Symptom Study Biobank". BMJ Public Health. 2 (1) e000478. doi:10.1136/bmjph-2023-000478. PMC 11812800. PMID 40018183.
The flow of currents within an axon can be described quantitatively by cable theory and its elaborations, such as the compartmental model. Cable theory was developed in 1855 by Lord Kelvin to model the transatlantic telegraph cable and was shown to be relevant to neurons by Hodgkin and Rushton in 1946. In simple cable theory, the neuron is treated as an electrically passive, perfectly cylindrical transmission cable, which can be described by a partial differential equation.
Ibrahim Ahmad Maqary - Professor of Arabic and linguistics, Current Co-imam of the Abuja National Mosque. Iya Abubakar – Professor of Mathematics at Ahmadu Bello University at the age of 28, first Northern-Nigerian to earn a PhD in any field, former vice-chancellor of Ahmadu Bello University R. A. B. Dikko - first Medical Doctor from Northern Nigeria. Mahmud Modibbo Tukur (1944–1988) -Nigerian historian, scholar and the 4th National President of the Academic Staff Union of universities (ASUU) Muhammad Ali Pate – CEO GAVI; Global Director for Health, Nutrition and Population at the World Bank, professor at Harvard Chan School; former Minister of State for Health, Current Minister Of Health. Mustafa Shehu - first person from Sub-Sahara Africa to be elected president of the World Federation of Engineering Organizations. Umar Garba - professor of electrical and telecommunications engineering, former executive vice-chairman and chief executive Officer of Nigerian Communications Commission Abdul Ganiyu Ambali - veterinary doctor, former vice- chancellor of University of Ilorin. Ibrahim Abubakar - professor of infectious disease epidemiology at University College London, vice provost (health). Fatima Batul Mukhtar - professor of botany, vice- chancellor Azman University. Bello Shehu - neurosurgeon, former chief medical director of the Usman Danfodiyo University Teaching Hospital, Sokoto, National Hospital, Abuja and Medical Director, Federal Medical Centre, Birnin-Kebbi, vice chancellor of The Federal University Birnin-Kebbi.
The sequencing platform to be used is chosen depending on different factors such as laboratory's research objectives, personal experience and skill levels. So far, the Illumina MiSeq system has proven to be the most commonly used platform for infectious disease research, pathogen surveillance, and pathogen discovery in research and public health. The instrument is compact enough to fit on a laboratory bench, has a fast runtime as compared to other similar platforms, and has a strong user support community. However, with further improvements of this technology and with additional error reduction and software stabilization, the MinION may be an excellent addition to the arsenal of current sequencing technologies for routine surveillance, especially in smaller laboratories with limited resources. For instance, the MinION was successfully used in the ZiBRA project for real-time Zika virus surveillance of mosquitoes and humans in Brazil, and in Guinea to perform real-time surveillance during the ongoing Ebola outbreak. In general, for limited resources IlluminaMiSeq, iSeq, Ion Torrent PGM, Oxford Nanopore, MinION are used. While for substantial resources Illumina NextSeq, NovaSeq, PacBio Sequel, Oxford Nanopore and PromethION are preferred.
Sources: en.wikipedia.org
Native GLP-1 is degraded within minutes by dipeptidyl peptidase-4 and neutral endopeptidases. Semaglutide carries a non-natural amino acid at position eight that blocks that cleavage, and a fatty diacid side chain that binds albumin. The result is a much longer duration of action than the native hormone.
The fatty diacid chain associates strongly with serum albumin, which keeps the peptide in circulation and shields it from rapid renal clearance. Bound peptide is released gradually, producing a sustained receptor signal. This mechanism also reduces the peak-to-trough variation seen with shorter-acting analogues.
The balance between peripheral receptor activation and signalling in the central nervous system is not fully resolved. The extent to which slowed gastric emptying accounts for reduced energy intake, compared with direct effects on appetite circuits, is debated. Long-term effects on lean mass and on tissues outside the gut and brain are still under study.
差别集中在三处：第 8 位残基被非天然氨基酸取代，第 34 位换成精氨酸，第 26 位增加一条脂肪酸侧链。前两处改动降低酶解速率，侧链则通过白蛋白结合延长循环时间。综合结果是半衰期从约两分钟延长到约一周。