The short version of Aib substitution fits in a sentence. The long version — which is the one that helps — is below.
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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.
Serum protein binding dominates the pharmacokinetic profile. The attached chain associates strongly with albumin, shielding the peptide from enzymatic attack and slowing filtration by the kidney. This interaction extends the circulation half-life to roughly one week in humans, which supports weekly administration intervals. An oral version pairs the peptide with an absorption enhancer that transiently alters gastric epithelium, permitting limited uptake; bioavailability by that route is substantially lower than by injection.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, a gut hormone released after meals. Its backbone retains the GLP-1 sequence but incorporates two substitutions that slow enzymatic breakdown by dipeptidyl peptidase-4. A short polyethylene glycol linker and a C18 fatty diacid are attached to the peptide chain, allowing the molecule to bind serum albumin and remain in circulation far longer than the native hormone. The result is a circulating half-life measured in days rather than the minutes typical of endogenous GLP-1.
Receptor activation occurs at GLP-1 receptors distributed across pancreatic islets, the hypothalamus, and the gastrointestinal tract. Binding triggers G protein signaling that raises cyclic AMP and enhances glucose-dependent insulin release. Because the effect depends on prevailing glucose levels, insulin secretion does not rise when blood sugar is already low. Signaling in the brain and gut also influences appetite and gastric emptying, which is why the compound appears in both metabolic and weight-related research literature.
Development began in the early 2010s with the goal of extending GLP-1 activity beyond the brief window achieved by native peptide infusion. The earliest approved formulation was a subcutaneous injection given once weekly. A later oral tablet pairs the peptide with an absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, usually shortened to SNAC. That carrier lowers local pH and helps the peptide cross gastric tissue. Both routes deliver the same active molecule.
| Property | Value | Notes |
|---|---|---|
| Molecular class | Synthetic peptide, GLP-1 receptor agonist | 31 amino acid residues |
| Molecular formula | C187H291N45O59 | free peptide, no counter-ion |
| Approximate mass | 4114 Da | matches theoretical value |
| Receptor target | Glucagon-like peptide-1 receptor | Gs-coupled, cyclic AMP pathway |
| Circulation half-life | About one week in humans | extended by albumin association |
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 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.
Clinical studies of semaglutide generally measure glycated hemoglobin, fasting plasma glucose, body weight, and composite cardiovascular endpoints. The SUSTAIN program enrolled adults with type 2 diabetes, while the STEP program focused on obesity without diabetes. Administration follows a stepwise escalation schedule designed to limit gastrointestinal effects during the first weeks. Reported outcomes include mean percentage weight change, the proportion of participants reaching defined weight-loss thresholds, and rates of nausea, vomiting, and diarrhea. Long-term data on durability after treatment stops are still limited and remain a topic of ongoing research.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, developed by Novo Nordisk and first approved in 2017 for type 2 diabetes. It belongs to the incretin mimetic class, a group of agents that reproduce the glucose-dependent actions of endogenous GLP-1. The molecule was engineered to resist degradation by dipeptidyl peptidase-4 and to bind serum albumin, extending its half-life from minutes to roughly one week. Approval for chronic weight management followed in 2021, based on large cardiovascular and obesity outcome trials.
GLP-1 receptors are expressed on pancreatic beta cells, in the gut, and in several brain regions. Receptor activation raises cyclic AMP, enhances glucose-dependent insulin secretion, and suppresses glucagon release when blood glucose is high. Effects on gastric emptying and on hypothalamic appetite circuits reduce energy intake. Because insulin release remains glucose-dependent, the risk of hypoglycemia is low when the drug is used alone. The precise contribution of each pathway to body weight change in humans remains an area of active investigation.
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.
Solid peptide material is generally kept at reduced temperature to limit degradation. Short-term storage at 2 to 8 degrees Celsius is common, while longer archival storage at minus 20 degrees Celsius or below is typical for lyophilised powder. Vials should remain sealed and protected from light, because ultraviolet exposure can oxidise susceptible residues. Repeated freeze-thaw cycles are avoided, as they promote aggregation and loss of soluble material. Solutions are less stable than solids and are usually prepared close to the time of use.
Reversed-phase high-performance liquid chromatography is widely used to assess purity and to separate the parent peptide from related substances. Mass spectrometry confirms identity and can resolve modifications that differ by a few daltons. Size-exclusion chromatography detects dimers and higher aggregates, which are relevant to both stability and immunogenicity questions. Peptide mapping with enzymatic digestion locates specific modifications along the sequence. Circular dichroism provides a secondary-structure profile, although it gives limited information about local conformational changes.
== Prevention == Cara Myer, the author of "The Tea and Toast Syndrome: Psychosocial Aspects of Congregate Dining" suggests that congregate dining for older adults may be an excellent strategy to prevent tea and toast syndrome. Myer mentions that social service interventions for malnutrition, including congregate dining, are often under-utilized and could provide a stimulating environment that may improve the quality of life of many older adults. Further, general preventative measures focus on evaluating the nutrition of older adults, including keeping a record of weight patterns, helping with meal plans focusing on nutrient-rich foods, and using local services such as a meal delivery program. Additional strategies include:
With Pillman injured, Austin joined Colonel Robert Parker's Stud Stable. After Pillman returned, the team was broken up when Austin turned on him, a decision Austin describes as a "mystery". Austin defeated Pillman in a singles match at Clash of the Champions XXV in November 1993.
== R == Rope bridge – Inca rope bridges were suspension bridges made from woven ichu grass, spanning canyons and rivers throughout the Andes. At their peak, at least 200 such bridges connected the Inca road system. Reed boats – a balsa was a boat that was constructed by pre-Columbian South Americans from woven reeds of totora bullrush. These reed boats varied in size from that of a small canoe used for navigation, transportation, and for small-scale fishing to large ships of up to 30 m (98 ft) in length, which were used for war, transportation, bulk goods hauling, and transporting royalty and nobility. They are still used today on Lake Titicaca in Peru and Bolivia by the indigenous peoples living along the banks of the lake. Rubber – the indigenous cultures of Mesoamerica were the first peoples in the world to extract the sap from rubber trees and then use it to make clothes, rubber balls to be played in ceremonial ball games, and many other utilitarian uses. Indigenous peoples, especially those who lived in the Amazon rainforest found many other uses for rubber. The science and technique of extracting sap from rubber trees and then using the sap to make goods made of rubber then spread to the high civilizations of the Andes and elsewhere in the Americas. Rubber balloons – the Olmec were the first people to use rubber balloons. Their civilization arose in 1700 BCE in the Yucatán Peninsula.
Sources: en.wikipedia.org
== Advertising == The company owns two blimps: the Bloomin' Onions I and II, both named after their appetizer. For several years, the company ran a media campaign with an Australian-themed variation of the Of Montreal composition "Wraith Pinned to the Mist (And Other Games)." General (Ret) Tommy Franks sits on the Board Of Directors for OSI Restaurant Partners, INC., which owns Outback Steakhouse.
Castor oil was the preferred lubricant for rotary engines, such as the Gnome engine after that engine's widespread adoption for aviation in Europe in 1909. It was used almost universally in rotary-engined Allied aircraft in World War I. Germany had to make do with inferior ersatz oil for its rotary engines, which resulted in poor reliability. The methanol-fueled, two-cycle, glow-plug engines used for aeromodelling, since their adoption by model airplane hobbyists in the 1940s, have used varying percentages of castor oil as lubricants. It is highly resistant to degradation when the engine has its fuel-air mixture leaned for maximum engine speed. Gummy residues can still be a problem for aeromodelling powerplants lubricated with castor oil, however, usually requiring eventual replacement of ball bearings when the residue accumulates within the engine's bearing races. One British manufacturer of sleeve valved four-cycle model engines has stated the "varnish" created by using castor oil in small percentages can improve the pneumatic seal of the sleeve valve, improving such an engine's performance over time. Castor oil is still occasionally used by aeromodellers in custom fuel mixtures for methanol-burning model engines, due to Castor oil's miscibility in methanol. Typical petroleum-derived two-stroke oils designed for gasoline engines are immiscible in methanol. Castor oil is a readily available alternative to PAG (Polyalkylene Glycol) or other specialty oils for mixing affordable glow fuel (commonly referred to as "nitro fuel" by aeromodelling hobbyists).
=== Infection === The use of greater amount of red blood cells has been suggested to increase the risk of infections, not only transfusion-transmitted infections, but also due to a phenomenon known as transfusion-related immunomodulation (TRIM). TRIM may be caused by macrophages and their byproducts. In those who were given red blood cells only with significant anemia ("restrictive" strategy), serious infection rates were 10.6% while in those who were given red blood at milder levels of anemia ("liberal" strategy), serious infection rates were 12.7%. On rare occasions, blood products are contaminated with bacteria. This can result in a life-threatening infection known as transfusion-transmitted bacterial infection. The risk of severe bacterial infection is estimated, as of 2020, at about 1 in 2,500 platelet transfusions, and 1 in 2,000,000 red blood cell transfusions. Blood product contamination, while rare, is still more common than actual infection. The reason platelets are more often contaminated than other blood products is that they are stored at room temperature for short periods of time. Contamination is also more common with longer duration of storage, especially if that means more than 5 days. Sources of contaminants include the donor's blood, donor's skin, phlebotomist's skin, and containers. Contaminating organisms vary greatly, and include skin flora, gut flora, and environmental organisms. There are many strategies in place at blood donation centers and laboratories to reduce the risk of contamination.
centriole A cylindrical organelle composed of microtubules, present only in certain eukaryotes. A pair of centrioles migrate to and define the two opposite poles of a dividing cell where, as part of a centrosome, they initiate the growth of the spindle apparatus.
Sources: en.wikipedia.org
=== Human === In humans (and perhaps in all placental mammals), the most common form is fetomaternal microchimerism (also known as fetal cell microchimerism or fetal chimerism) whereby cells from a fetus pass through the placenta and establish cell lineages within the mother. Fetal cells have been documented to persist and multiply in the mother for several decades. The exact phenotype of these cells is unknown, although several different cell types have been identified, such as various immune lineages, mesenchymal stem cells, and placental-derived cells. A 2012 study at the Fred Hutchinson Cancer Research Center, Seattle, has detected cells with the Y chromosome in multiple areas of the brains of deceased women. Fetomaternal microchimerism occurs during pregnancy and shortly after giving birth for most women. However, not all women who have had children contain fetal cells. Studies suggest that fetomaternal microchimerism could be influenced by killer-cell immunoglobulin-like (KIR) ligands. Lymphocytes also influence the development of persisting fetomaternal microchimerism since natural killer cells compose about 70% of lymphocytes in the first trimester of pregnancy. KIR patterns on maternal natural killer cells of the mother and KIR ligands on the fetal cells could have an effect on fetomaternal microchimerism. In one study, mothers with KIR2DS1 exhibited higher levels of fetomaternal microchimerism compared to mothers who were negative for this activating KIR. The potential health consequences of these cells are unknown.
== Consumption == Worldwide sugar provides 10% of the daily calories (based on a 2000 kcal diet). In 1750 the average Briton got 72 calories a day from sugar. In 1913 this had risen to 395. In 2015, sugar still provided around 14% of the calories in British diets. According to one source, per capita consumption of sugar in 2016 was highest in the United States, followed by Germany and the Netherlands.
=== December === 1 December – Everton Football Club launch an appeal against the decision to dock them ten Premier League points. 2 December – Havering London Borough Council reverses its decision to cancel the display of Hanukkah candles outside its town hall, having previously said the display would not go ahead because of "escalating tensions from the conflict in the Middle East". Police declare a major incident in Cumbria, which is affected by heavy snowfall. As much as 30 cm has fallen by the following day. 5 December – Junior doctors in England will stage further strike action after rejecting the latest pay offer, the British Medical Association confirms, with a three-day strike scheduled to begin on 20 December and a six-day strike scheduled to begin on 3 January 2024. A woman, later named as Lianne Gordon, is shot dead in an incident in east London. A teenage boy and a man are also injured in the shooting. 6 December – Mayor of the West Midlands Andy Street confirms the Home Secretary has authorised his application to have the powers of the West Midlands Police and Crime Commissioner subsumed into his mayoral role from May 2024. 7 December – An inquest into the death of Ruth Perry rules that an Ofsted report "likely contributed" to the head teacher taking her life in January 2023. Six former Metropolitan Police officers are given suspended sentences after sending racist, sexist and homophobic WhatsApp messages. 9 December – A 16-year-old boy is charged with the murder of Lianne Gordon.
=== 1890s === 1890: Austrian-born chemist Ida Freund became the first woman to work as a university chemistry lecturer in the United Kingdom. She was promoted to full lecturer at Newnham College, Cambridge. 1890: British popular science educator and author Agnes Giberne co-founded the British Astronomical Association. Subsequently, English astronomer Elizabeth Brown was appointed the director of the association's Solar Section, well known for her studies in sunspots and other solar phenomena. 1890: British mathematician Philippa Fawcett became the first woman to obtain the highest score in the Cambridge Mathematical Tripos examinations, a score "above the Senior Wrangler". (At the time, women were ineligible to be named Senior Wrangler.) 1891: American-born astronomer Dorothea Klumpke was appointed as Head of the Bureau of Measurements at the Paris Observatory. For the next decade, in addition to completing her doctorate of science, she worked on the Carte du Ciel mapping project. She was recognized for her work with the first Prix de Dames award from the Société astronomique de France and named an Officier of the Paris Academy of Sciences. 1892: American psychologist and logician Christine Ladd-Franklin presented her evolutionary theory on the development of colour vision to the International Congress of Psychology. Her theory was the first to emphasize colour vision as an evolutionary trait. 1893: Florence Bascom became the second woman to earn her PhD in geology in the United States, and the first woman to receive a PhD from Johns Hopkins University.
==== Singles ==== "Moth/Lake" (2015, Boomkat Editions) "Flora's Theme" (2016, Williams Street Records) "Final Exam" with Kelela and Adrian Piper (2016, The Vinyl Factory) "Solilunita" (2018, Break World Records)
Sources: en.wikipedia.org
It is a synthetic peptide of 31 amino acids, built to resemble the natural incretin hormone GLP-1. Because of its size and composition it is handled analytically like other therapeutic peptides, using chromatographic and mass spectrometric methods rather than the techniques typical of small organic drugs.
The substitution at position 8 removes the site recognised by dipeptidyl peptidase-4, the enzyme that destroys the native hormone within minutes. The linked lipophilic chain then binds circulating albumin, which further limits access by degradative enzymes and reduces renal loss. Together these features lengthen the effective circulation time considerably.
It acts at the glucagon-like peptide-1 receptor, a G protein-coupled receptor that signals mainly through cyclic AMP. Activation is glucose dependent, meaning insulin release is stimulated more strongly when blood glucose is already elevated. Other tissues carrying the same receptor respond as well, which explains effects beyond glucose control.
Native GLP-1 is degraded within minutes by circulating enzymes. The synthetic version carries substitutions at positions that block enzymatic cleavage, plus a fatty acid side chain that promotes albumin binding. These two changes together extend circulation time from minutes to roughly a week.