Everything below concerns incretin. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2026-03-08. Numbers and descriptions here follow the published literature rather than marketing material.
Semaglutide is a synthetic peptide analog of glucagon-like peptide-1, a hormone released from intestinal L-cells after food intake. It contains 31 amino acids and differs from native GLP-1 through modifications that slow enzymatic breakdown. The peptide was developed to extend the short circulating half-life of endogenous GLP-1, which is measured in minutes. Researchers introduced the compound in the early 2010s. Two backbone changes and a fatty acid side chain define its structure, distinguishing it from earlier GLP-1 receptor agonists.
The compound binds the GLP-1 receptor on pancreatic beta cells and other tissues, activating a G-protein signaling cascade that raises intracellular cyclic AMP. This action increases glucose-dependent insulin secretion when blood glucose is elevated, while binding also slows gastric emptying and reduces glucagon release. In the central nervous system, receptor activation in the hypothalamus and brainstem contributes to reduced appetite. The fatty acid chain binds albumin, which protects the peptide from renal filtration and enzymatic degradation. This albumin binding is central to its extended circulation time.
Native GLP-1 is degraded rapidly by dipeptidyl peptidase-4. Semaglutide resists this cleavage because alanine at position 8 is replaced by alpha-aminoisobutyric acid. A second substitution at position 34 introduces arginine, which further stabilizes the peptide. The most distinctive modification is a spacer and C18 fatty diacid attached at lysine 26, enabling strong albumin affinity. These three changes together produce a half-life measured in days rather than minutes, and the same structural logic underlies other long-acting analogs in this class.
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.
| Property | Value | Notes |
|---|---|---|
| Molecular class | Synthetic peptide | 31 amino acids |
| Backbone modification | Aib at position 8 | Blocks DPP-4 cleavage |
| Fatty acid chain | C18 diacid | Supports albumin binding |
| Native half-life | 1 to 2 minutes | Endogenous GLP-1 |
| Analog half-life | Approximately one week | Extended by albumin binding |
Degradation proceeds along several parallel routes. Deamidation of asparagine and glutamine residues generates charged variants that shift retention time in chromatographic analysis. Oxidation targets methionine and can be accelerated by trace metals or dissolved oxygen. Non-covalent aggregation produces dimers, oligomers, and larger species that are difficult to reverse. Isomerisation at aspartate residues is slower but measurable under thermal stress. The distribution among these pathways depends on pH, buffer composition, ionic strength, and the presence of excipients such as sugars or surfactants.
Reverse-phase high-performance liquid chromatography with ultraviolet detection near 214 nm is the standard purity method, reported as area percent. Mass spectrometry, usually with electrospray ionisation, confirms identity and reveals covalent modifications. Size-exclusion chromatography quantifies aggregates and fragments. Peptide mapping after enzymatic digestion localises changes to specific sequence regions. Circular dichroism and infrared spectroscopy report on secondary structure, while light scattering tracks particle formation in liquid formulations. No single technique captures every quality attribute.
Quality control relies on pharmacopoeial monographs where they exist, combined with in-house specifications for identity, purity, water content, and counter-ion composition. Reference standards allow calibration across laboratories, although certified materials for every analogue are not universally obtainable. Batch records, chromatograms, and mass spectra form the documentation trail. Regulatory classification varies by jurisdiction and intended use, and research-grade material differs from pharmaceutical-grade material in testing scope. Analytical uncertainty is often expressed as relative standard deviation across replicate injections.
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.
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.
There are many reasons why an excited state can be metastable. The most common mechanism is by suppression of gamma decay of excited nuclei, making the decay route a forbidden transition. Spin is conserved, and a photon has spin 1 ħ. Thus, if a decay route would require a change of ≥ 2 ħ (any possible change is always integer) in angular momentum, then the gamma decay would become highly suppressed. For example, if the decay requires the nucleus to change spin by 2 ħ, then it must emit 2 photons at once. This is a 3-body interaction, which is much weaker than a 2-body interaction, and thus occurs at a much lower rate. In general, each additional unit of spin larger than 1 that the emitted gamma ray must carry inhibits decay rate by about 5 orders of magnitude. As the excited energy state lowers, eventually internal conversion (IC) and internal pair production (IP) takes over. The decay of 180mTa from spin-9 state to spin-2 state changes spin by 7 ħ. This suppresses the rate of gamma emission so much that the decay rate is essentially equal to the rate of IC, in agreement with the above. When the nucleus begins and ends with 0 spin, it cannot decay via single photo gamma emission. The only possible routes are IC, internal pair production, or two-photon gamma emission. Usually IC and IP dominates over two-photon gamma emission.
== External links == Overview of all the structural information available in the PDB for UniProt: P09958 (Human Furin) at the PDBe-KB. Overview of all the structural information available in the PDB for UniProt: P23188 (Mouse Furin) at the PDBe-KB.
Administration: Administers the Secretariat as well as looks after personal matters of the Chairman/Members and other Officers/Staff of the commission. All India Services: Recruitment to All India Services is done either by direct recruitment, through Civil Services Examination or by promotion from the State Service. The AIS Branch handles the promotions of State Service officers to the IAS, IPS and IFS. It also handles policy matters relating to All India Services and amendments in the 'Promotion Regulations' of respective services. Appointments: It carries out appointments to central services based on Promotion (based on proposals from various Ministries/Departments/Union Territories and from certain local bodies) and by the means of Deputation and Absorption. Examinations: It carries out merit-based selection and recommendation of candidates through various examinations such as the Engineering Services Examination, Combined Medical Services Examination, Defence Services Examination, Civil Services Examination, etc., to Group A and Group B Services of the Government of India. General: Primarily deals with day-to-day housekeeping work for the Commission, such as arrangements and facilitation for the conduct of Examinations by the UPSC, printing the Annual Report, etc.
In 2013, researchers demonstrated graphene's high mobility in a detector that allows broad band frequency selectivity ranging from the THz to IR region (0.76–33 THz) A separate group created a terahertz-speed transistor with bistable characteristics, which means that the device can spontaneously switch between two electronic states. The device consists of two layers of graphene separated by an insulating layer of boron nitride a few atomic layers thick. Electrons move through this barrier by quantum tunneling. These new transistors exhibit negative differential conductance, whereby the same electric current flows at two different applied voltages. In June, an 8 transistor 1.28 GHz ring oscillator circuit was described. The negative differential resistance experimentally observed in graphene field-effect transistors of conventional design allows for construction of viable non-Boolean computational architectures. The negative differential resistance—observed under certain biasing schemes—is an intrinsic property of graphene resulting from its symmetric band structure. The results present a conceptual change in graphene research and indicate an alternative route for graphene applications in information processing. In 2013 researchers created transistors printed on flexible plastic that operate at 25 gigahertz, sufficient for communications circuits and that can be fabricated at scale. The researchers first fabricated non-graphene-containing structures—the electrodes and gates—on plastic sheets.
Sources: en.wikipedia.org
==== Fibres ==== Fibres found in the extracellular matrix are collagen fibers, elastic fibers, and reticular fibers. Collagen fibres are fixated in intercellular spaces via ground substance, a clear, colorless, and viscous fluid containing glycosaminoglycans and proteoglycans.
== Laboratory measurement == The reference range for prothrombin time depends on the analytical method used, but is usually around 12–13 seconds (results should always be interpreted using the reference range from the laboratory that performed the test), and the INR in absence of anticoagulation therapy is 0.8–1.2. The target range for INR in anticoagulant use (e.g. warfarin) is 2 to 3. In some cases, if more intense anticoagulation is thought to be required, the target range may be as high as 2.5–3.5 depending on the indication for anticoagulation.
=== Eyes === Isotretinoin and other retinoids are well known to affect the eyes. Dry eyes are very common during treatment and is caused by isotretinoin's apoptotic effect on the meibomian glands. Some people develop contact lens intolerance as a result. In some people, these changes are long-lasting or irreversible and represent Meibomian Gland Dysfunction (MGD). Other common effects on the eyes include inflammation of the eyelid (blepharitis), red eye caused by conjunctivitis and irritation of the eye. More rare ocular side effects include blurred vision, decreased night vision (which may be permanent), colour blindness, development of corneal opacities, inflammation of the cornea (keratitis), swelling of the optic disk (papilloedema, associated with IIH), photophobia and other visual disturbances.
=== Biological slug mucus === Mucus from gastropods is composed of a combination of water and glycoproteins, enzymes, and trace amounts of metal ions. Mucin glycoproteins, like achacin and glycosaminoglycans (GAGs) like hyaluronic acid are the primary components of mucus, contributing to its antimicrobial properties. Amino groups interact with the sulfate and carboxyl groups found in the glycosaminoglycans to promote bonding and hydrophobic interactions during gel formations. Other molecules like allantoin, or 5-ureidohyantoin, can be found in slug mucus to prompt cell proliferation and wound healing, as well as collagen synthesis, respectively. Significant amounts of zinc, iron, copper, and manganese metal ions are typically found in the chemical composition of slug mucus.
29 November – MPs vote 330 to 275 in favour of proposals to allow assisted dying in England and Wales. The bill passes the first stage in the Commons but will be followed by months of parliamentary activity before needing the approval of both houses of parliament for it become law. Louise Haigh resigns as Secretary of State for Transport after a past fraud offence comes to light. She is replaced by Heidi Alexander.
Sources: en.wikipedia.org
About 1,500 heat-related deaths occurred in the Netherlands, again largely the elderly. The heat wave broke no records, although four tropical weather-designated days in mid-July, preceding the official wave, are not counted due to a cool day in between and the nature of the Netherlands specification/definition of a heat wave. The highest temperature recorded this heatwave was on 7 August, when in Arcen, in Limburg, a temperature of 37.8 °C (100.0 °F) was reached, 0.8 °C below the national record (since 1904). A higher temperature had only been recorded twice before. On 8 August, a temperature of 37.7 °C (99.9 °F) was recorded, and 12 August had a temperature of 37.2 °C (99.0 °F). Initially, 141 deaths were attributed to the heat wave in Spain. A further research of INE estimated a 12,963 excess of deaths during summer of 2003. Temperature records were broken in various cities, with the heat wave being more felt in typically cooler northern Spain. Record temperatures were felt in:
== Definition == Natural uranium contains about 0.72% 235U. Depleted uranium has lower mass fractions—up to three times less—of 235U and 234U than natural uranium. Since 238U has a much longer half-life than the lighter isotopes, DU is about 40% less radioactive than natural uranium. Most of the alpha radiation comes from 238U and 234U whereas beta radiation comes from decay products 234Th and 234Pa that are formed within a few weeks. The United States Nuclear Regulatory Commission (NRC) defines depleted uranium as uranium with a percentage of the 235U isotope that is less than 0.711% by weight (see 10 CFR 40.4). The military specifications designate that the DU used by the U.S. Department of Defense (DoD) contain less than 0.3% 235U. In actuality, DoD uses only DU that contains approximately 0.2% 235U.
=== Pharmacokinetics === When taken by mouth, canagliflozin reaches highest blood plasma concentrations after one to two hours and has an absolute bioavailability of 65%, independently of food intake. When in the bloodstream, 99% of the substance are bound to plasma proteins, mainly albumin. It is metabolized mainly by O-glucuronidation via the enzymes UGT1A9 and UGT2B4, and by hydroxylation to a lesser extent. The terminal half life is 10.6 hours for a 100 mg dose and 13.1 hours for a 300 mg dose, with 43% being excreted in the faeces (mostly in unchanged form) and 33% in the urine (mostly as glucuronide).
=== Amino acid deficiencies === In bacteria and yeast, codon reassignment can be caused by a shortage of required amino acids. Instead of halting protein production all together, tRNA molecules select another amino acid to add to the amino acid chain. This amino acid may have similar properties to the intended amino acid, or it may not. This may cause deformities in the proteins, making them less efficient or even nonfunctional. A hypothesis as to why this phenomenon persists despite the loss of efficiency is that it is preferable for the organism to have a worse version of the protein than to have no protein at all. In some human cancer cells, such as melanoma cells, a similar tactic is used. As an immune response, to try and destroy the cancer, T cells release an enzyme that destroys the essential amino acid tryptophan within the cancer cells. This typically deprives the cancer of many key proteins, killing the cancer cells. However, some cancer cells are able to use codon reassignment to replace the tryptophan with a similar amino acid called phenylalanine. This amino acid replacement and resulting functional protein allows the cancer cell to survive and continue dividing.
Another similar characterization concerns the exradii ra, rb, rc, and rd in the same four triangles (the four excircles are each tangent to one side of the quadrilateral and the extensions of its diagonals). A quadrilateral is tangential if and only if
Sources: en.wikipedia.org
It is a synthetic analog of GLP-1 produced through medicinal chemistry to resist enzymatic degradation. The design goal was longer circulation than the native hormone.
A fatty acid side chain attaches the peptide to serum albumin, which shields it from kidney filtration and protease activity. This interaction is the main reason its circulation time is extended.
No. The native hormone is GLP-1, and semaglutide is an engineered variant with three deliberate structural alterations. It does not appear in unmodified biological sources.
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.