incretin comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Last reviewed on 2026-08-01. Where a claim depends on a specific study, the study is described rather than over-claimed.
当前公开资料把 tirzepatide 归为肠促胰素类受体双重激动剂。它并非激素天然变体，而是经过序列改造的工程化肽。其分子量、等电点与疏水性等基础参数已在药典和化学数据库中收录，可作为分析检测和质量研究的参照。
Tirzepatide 是一种由 39 个氨基酸组成的合成肽，分子结构上以 GIP 序列为骨架并引入脂肪酸侧链修饰，使其能够同时与葡萄糖依赖性促胰岛素多肽（GIP）受体和胰高血糖素样肽-1（GLP-1）受体结合。这种双重激动特性使它在同类肽类药物中区别于选择性 GLP-1 受体激动剂。该分子最早由一家制药公司在 2010 年代报道，随后进入糖尿病与体重管理领域的临床研究。
Published work supports the view that engaging two incretin receptors produces changes in glucose handling and body weight larger than those seen with single-receptor activation. Why that difference arises is not fully settled. Open questions include how much of the observed weight effect depends on central versus peripheral signaling, and whether the two receptors form interacting complexes. Most reported findings come from controlled trials and animal models, and translation between species is imperfect. Further research is expected to refine these points over time.
Tirzepatide is a synthetic peptide built from 39 amino acid residues. Its sequence is related to human glucose-dependent insulinotropic polypeptide, with modifications that include a C-terminal extension and a C20 fatty diacid joined through a linker. Those changes raise the molecule's affinity for serum albumin, which slows renal filtration and lengthens the time it stays in circulation. The free base has an average molecular mass near 4813.5 daltons. The compound is made by solid-phase peptide synthesis followed by chromatographic purification.
| Property | Value | Notes |
|---|---|---|
| 分子类型 | 合成修饰肽 | 39 个氨基酸，含脂肪酸侧链 |
| 受体靶点 | GIP 与 GLP-1 受体 | 双重激动剂 |
| 分子量 | 约 4.8 kDa | 以游离肽计 |
| 外观 | 白色至类白色粉末 | 冻干形态常见 |
| 溶解性 | 可溶于水及水性缓冲液 | 溶解后宜低温保存 |
Pharmacologically, tirzepatide activates two distinct G protein-coupled receptors: the glucose-dependent insulinotropic polypeptide receptor and the glucagon-like peptide-1 receptor. Binding at each target triggers cyclic AMP accumulation and downstream signaling in pancreatic beta cells, adipose tissue and the central nervous system. Because the two pathways overlap only partially, the combined effect on insulin secretion, glucagon suppression and appetite signaling differs from that of selective single-receptor compounds. Affinity is not equal across the two targets, and the clinical meaning of that imbalance remains an area of active study.
Clinical research programs have evaluated tirzepatide in adults with type 2 diabetes and in adults with obesity or excess weight. Trials generally reported reductions in glycated hemoglobin and body weight across treatment periods of several months. Since these studies enrolled defined populations under controlled conditions, the findings describe group averages rather than individual outcomes. Open questions include the durability of effects after treatment stops, variation among subgroups, and the long-term consequences of sustained dual receptor stimulation. Published trial summaries should be consulted for exact measurements rather than secondary accounts.
The peptide backbone contains 39 amino acids and includes alpha-aminoisobutyric acid residues, which are not among the standard proteinogenic set. A C20 fatty diacid moiety is attached through a linker, allowing the compound to bind serum albumin and extend its circulation time. This albumin binding is the main reason the molecule supports once-weekly administration rather than more frequent dosing. The measured molecular mass is approximately 4,813 daltons, placing it firmly in the peptide rather than small-molecule class.
Tirzepatide is a synthetic peptide that activates both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. This dual agonist profile distinguishes it from earlier incretin-based compounds that act on a single receptor. The molecule was engineered from the native GIP sequence and carries several non-natural residues that slow enzymatic breakdown. Researchers designed it to combine the insulinotropic effects of GIP signaling with the appetite and gastric-emptying effects associated with GLP-1 activation.
After subcutaneous injection, absorption is gradual, and peak plasma levels are generally reached within one to three days. Albumin binding extends the apparent half-life to roughly five days, which supports a weekly administration schedule. Metabolism proceeds mainly through proteolytic cleavage of the peptide backbone and beta-oxidation of the fatty acid chain, rather than through cytochrome P450 pathways. Eliminated fragments are largely recycled through general protein turnover, and excretion of intact drug in urine is minimal. These properties distinguish the molecule from short-acting incretin mimetics.
Tirzepatide is a synthetic peptide of 39 amino acids engineered from the native glucose-dependent insulinotropic polypeptide sequence. Its structure incorporates several non-natural residues and a C-terminal segment derived from glucagon-like peptide-1, together with a C20 fatty diacid moiety attached through a linker. The lipophilic side chain promotes binding to serum albumin, which slows renal clearance after administration. The compound is classified as a dual incretin receptor agonist and is supplied as a lyophilized powder for reconstitution or as a preformulated solution, depending on the presentation.
==== Viral transduction ==== Viral transduction is a method that uses viral vectors and is used for the stable introduction of genes into the target cells. In this method, the viral vector (virion) infects host cells that by directly transporting DNA into the nucleus of the cell. Two common types of viruses used for transduction are adenoviruses, which tend to be transient, and lentiviruses, which integrate the DNA into the genome. Lentiviral vectors have also been an attractive viral tool because they can transduce in non-dividing cells, allowing for stable transfer in a large range of host cell types.
=== Laboratory synthesis === The chemical synthesis of DMT has been described. It can be synthesized through several possible pathways from different starting materials. The two most commonly encountered synthetic routes are through the reaction of indole with oxalyl chloride followed by reaction with dimethylamine and reduction of the carbonyl functionalities with lithium aluminium hydride to form DMT. The second commonly encountered route is through the N,N-dimethylation of tryptamine using formaldehyde followed by reduction with sodium cyanoborohydride or sodium triacetoxyborohydride. Sodium borohydride can be used but requires a larger excess of reagents and lower temperatures due to it having a higher selectivity for carbonyl groups as opposed to imines. Procedures using sodium cyanoborohydride and sodium triacetoxyborohydride (presumably created in situ from cyanoborohydride though this may not be the case due to the presence of water or methanol) also result in the creation of cyanated tryptamine and beta-carboline byproducts of unknown toxicity while using sodium borohydride in absence of acid does not. Bufotenine, a plant extract, can also be synthesized into DMT. Alternatively, an excess of methyl iodide or methyl p-toluenesulfonate and sodium carbonate can be used to over-methylate tryptamine, resulting in the creation of a quaternary ammonium salt, which is then dequaternized (demethylated) in ethanolamine to yield DMT. The same two-step procedure is used to synthesize other N,N-dimethylated compounds, such as 5-MeO-DMT.
Wolpoff, anthropologist of the University of Michigan; John Shea (archaeologist), anthropologist of Stony Brook University; Lewis Binford, anthropologist of Southern Methodist University in Texas; Neanderthals are thought to have lived similar unevolved uncultured lives for 200,000 years; Brigitte Delluc of Abri Pataud; in the 1980s, a completely new paradigm was thought up by British anthropologist Chris Stringer whereby a new group originated about 200,000 years ago, replacing the former human evolution, known as recent African origin of modern humans, but this paradigm was countered by Milford Wolpoff and his multiregional origin of modern humans, arguing that Neanderthals hadn't died out; Dorothy Garrod, the first female professor at the University of Cambridge in 1939 - the Disney Professor of Archaeology, completed important research in the middle East on how Neanderthals would have encountered much more culturally advanced modern humans in that region; archaeologist Ofer Bar-Yosef described how radiocarbon dating does not work beyond 50,000 years, and modern humans were found there at least 100,000 years ago; the dating methods remained in dispute until reliable genetic ancestry methods arrived in the late 1980s, with Mark Stoneking, a molecular anthropologist of Penn State University, who introduced the Mitochondrial Eve theory in 1987; geneticist Kenneth Kidd and how genetic data had superseded much of the anthropological research, which had been inherently unreliable due to not enough solid data; essentially Neanderthals died out possibly due to insufficient language ability, and were less able in overall cognitive planning. Directed by Lawrence Simanowitz, narrated and produced by William Woollard, made by InCA Productions 6 October Staying Alive, survivors of terrible accidents speak, with Sylvia Chapell of the August 1985 British Airtours Flight 28M; Paul Barney of the September 1994 Sinking of the MS Estonia; survival cognitive psychologist John Leach of Lancaster University; Robert Sapolsky, a neuroendocrinologist, on how glucocorticoids are secreted; Jeffrey Alan Gray, Professor of Psychology at the Institute of Psychiatry, Psychology and Neuroscience; the 336th Training Group at Fairchild Air Force Base; medical researchers at DRDC Toronto; the October 1991 Operation Boxtop 435 Transport and Rescue Squadron from CFB Trenton Hercules crash, which resulted in the 1993 film Ordeal in the Arctic; the brain neurotransmitters affect survival outcomes, controlled by the enzyme monoamine oxidase; Helicopter Underwater Escape Training at Survival Systems in Dartmouth, Nova Scotia. Narrated by Bill Paterson, the consultant was Edward Bullmore, directed by Denman Rooke, produced by Adam Bullmore, made by October Films 13 October Killer Bees, about a catastrophic genetic experiment in southern Brazil in the late 1950s - the Africanized bee; the East African lowland honey bee was introduced in 1956 by Warwick Estevam Kerr; the bees were introduced to help the honey industry, instead the new bees killed off the native bees, as well as many people too, with bees terrorising Apache Junction, Arizona; one swarm of thousand led to 20,000 other swarms in one year; the bees have killed over 600 people; a climber in Costa Rica disturbed a swarm, and received 8,000 stings, killing him. Directed by Martin Gorst, made by Windfall Films 27 October Double Identity, largely about the nature versus nurture argument, as opposed to the less-scientific tabula rasa argument; the Twins Days annual festival held in Twinsburg, Ohio; the heritability of IQ and Robert Plomin of the Institute of Psychiatry, Psychology and Neuroscience at King's College London; Nick Martin of the Queensland Institute of Medical Research; 75% of intelligence is genetic from twin studies, and David T. Lykken of the University of Minnesota; vanishing twins; Neil Sebire of King's College Hospital and Alessandra Piontelli of the University of Milan; country music The LeGarde Twins; Dorothy V. M. Bishop of the University of Cambridge; heritability of IQ and Peter Conrad (sociologist) of Brandeis University; the Louisville Twin Study at the University of Louisville in Kentucky, which also found the Scarr–Rowe effect. Narrated by Jenni Murray, directed by Selina Macnair, produced by Amanda Theunissen, made by Fulcrum Productions West 3 November Identified Flying Objects, about Marfa, Texas and the Marfa lights, and other earthquake lights; Paul Devereux and computer scientist Erling Strand, of Østfold University College and Project Hessdalen, visits the Min Min lights in Australia in 1995; Paul Devereux investigated lights that had been seen at Llanegryn in 1904, which followed the Mochras geological fault; there had been seismic activity at the time which had culminated in the 1906 Swansea earthquake; lights had been seen at Toppenish ridge in the US, in the Cascade Mountains, which had a thrust fault; geologist Peter Sammonds at the UCL Department of Earth Sciences; geophysicist Jim Byerlee, known for Byerlee's law; Mexican television presenter Jaime Maussan; the Popocatépetl volcano in Mexico. 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Directed by Edmund Coulthard, produced by Duncan Dallas, who founded Café Scientifique in 1998, made by XYTV 24 November The Men with Nine Lives, about the British Army bomb disposal course, with 321 EOD Squadron RLC and the Army School of Ammunition (now the Defence Explosive Ordnance Disposal, Munitions and Search Training Regiment); twenty British Army bomb disposal personnel were killed defusing bombs in Northern Ireland; early IRA explosives were in tin cans filled with nails; 42-year-old Shane O'Doherty, a former IRA operative, who received thirty life sentences in 1974 for letter bombs; IRA personnel called themselves 'explosive operatives'; the IRA moved on to bombs in mail packages, triggered by tilt switches, and on to much-bigger car bombs; Lieutenant-Colonel Peter Miller invented a remote-control mechanical device that could set off a controlled explosion, so disabling most of the bomb components; projected water disruptors could remove explosive devices under vehicles; the IRA put car explosive devices inside a half of a beer keg; letter bombs would contain three to four ounces of semtex (mostly pentaerythritol tetranitrate); the Downing Street mortar attack of 7 February 1991; the hostage bomb; the IRA would lure army bomb disposal personnel, and metal-detectors would find how the IRA had lured army personnel; south Armagh, controlled by the Provisional IRA South Armagh Brigade was the most-dangerous part of Northern Ireland, and all army personnel travelled on operations only by helicopter. Directed by David Dugan, made by Windfall Films. Shown on Nova on 21 October 1997 as Bomb Squad 1 December Day Return to Space about the new proposals for craft; in 1995, NASA proposed the X-33, chosen on 2 July 1996, to fly by March 1999; Daniel Goldin, head of NASA from 1992 to 2001; Saturn from The Planets; The Blue Danube; the McDonnell Douglas DC-X; Maxwell Hunter; Jupiter from The Planets; Hans Mark of NASA; David Urie and Paul Landry; the Rutan Voyager, which flew around the world without refuelling; the aerospike engine; the Ansari X Prize and the EAA AirVenture Oshkosh air show; Mitchell Burnside Clapp; Gary Hudson, Bevin McKinney, and their Rotary Rocket (Roton); Steve Bennett and his Starchaser Industries. Narrated, similarly to the Adam Curtis series, by Jack Fortune, produced by Richard Reisz, directed by Stephen White, made by TV6 8 December Superhighway Robbery, about 26-year-old Russian computer programmer Vladimir Levin and computer hacking, who was caught when he arrived at Stansted Airport in March 1995 (he was trying to evade extradition to the US, but failed and was extradited in September 1997; an average bank robbery took $1900, but was prosecuted around 82%, a robbery via computer took around $250,000 and prosecution was around 2%; Willie Sutton and his Sutton's law. Narrated by Robin Ellis, directed by Patrick Forbes, produced by Jenny Crowther, made by Hart Ryan. 15 December Dr Satan's Robot, it refers to the film Mysterious Doctor Satan; it shows surgeon Robert J. White and his many macabre experiments on animals; the documentary would have not been appointment viewing for supporters of PETA; John Frankenheimer, director of the film Island of Dr Moreau; Terry Gilliam and his film Twelve Monkeys; the film The City of Lost Children; novelist Michael Marshall Smith, and his novel Spares; Cold Lazarus by Dennis Potter; Conservative MP for Birmingham Edgbaston, Jill Knight, and her disagreements with Roger Gosden; John Gillott; film director John Carpenter; David King, and disagreements with Robert Plomin, which led to his MRC funding being withheld; James Wilson (scientist) of the Perelman School of Medicine at the University of Pennsylvania; Julliet Tizzard of the Progress Trust. Narrated by Seán Barrett (actor), produced by Cathy Rogers, directed by Martin Durkin, made by RDF Television, with the Learning Channel
=== Of miscellaneous things === Foodomics was defined by Alejandro Cifuentes in 2009 as "a discipline that studies the food and nutrition domains through the application and integration of advanced omics technologies to improve consumer's well-being, health, and knowledge." Inspired by foundational questions in evolutionary biology, a Harvard team around Jean-Baptiste Michel and Erez Lieberman Aiden created the American neologism culturomics for the application of big data collection and analysis to cultural studies.
=== MSIR model === For many infections, including measles, babies are not born into the susceptible compartment but are immune to the disease for the first few months of life due to protection from maternal antibodies (passed across the placenta and additionally through colostrum). This is called passive immunity. This added detail can be shown by including an M class (for maternally derived immunity) at the beginning of the model.
Sources: en.wikipedia.org
== Early life and education == Esimone was born on 29 December 1970 in Tiko, Cameroon. He earned a Bachelor of Pharmacy degree from the University of Nigeria Nsukka in 1995, followed by postgraduate studies in pharmaceutical microbiology and pharmaceutics, completing a PhD in 2002.
=== International locations === The first location outside of North America opened in the United Kingdom on July 4, 2013, in London on Long Acre in Covent Garden. The chain now has more than 170 restaurants in the United Kingdom. In 2017, Five Guys opened its first restaurants in Germany, with a branch in Frankfurt and another in Essen. Five Guys opened its first Korean store in Gangnam, Seoul in 2023, with a countdown shout, and expanded to four branches in Seoul. In 2021, Five Guys opened their first location in Australia. The chain also has plans to expand into New Zealand. In 2025, Five Guys announced that it would open their first restaurant in Denmark, at Fisketorvet, a shopping mall in Copenhagen. In 2026, the number of stores per country was as follows:
== Further reading == Bud, Robert. "Biotechnology in the Twentieth Century." Social Studies of Science 21.3 (1991), 415–457 doi:10.1177/030631291021003002. Bud, Robert (1989). "History of 'biotechnology". Nature. 337 (6202): 10. Bibcode:1989Natur.337...10B. doi:10.1038/337010a0. PMID 2909886. S2CID 4354445. Dronamraju, Krishna R. Biological and Social Issues in Biotechnology Sharing. Brookfield: Ashgate Publishing Company, 1998. ISBN 9781840148978. Feldbaum, Carl (2002). "Some History Should Be Repeated". Science. 295 (5557): 975. doi:10.1126/science.1069614. PMID 11834802. S2CID 32595222. Rasmussen, Nicolas, Gene Jockeys: Life Science and the rise of Biotech Enterprise, Johns Hopkins University Press, (Baltimore), 2014. ISBN 978-1-42141-340-2.
PABA is an intermediate in the synthesis of folate by bacteria, plants, and fungi. Many bacteria, including those found in the human intestinal tract such as E. coli, generate PABA from chorismate by the combined action of the enzymes 4-amino-4-deoxychorismate synthase and 4-amino-4-deoxychorismate lyase. Plants produce PABA in their chloroplasts, and store it as a glucose ester (pABA-Glc) in their tissues. The malarial protozoan Plasmodium only make PABA when necessary, preferring to get it from the surroundings if able to. Some bacteria, including a few found in the human microbiome, are unable to make PABA for themselves but can use PABA to make folate. A few are very efficient at the PABA-to-folate conversion despite not making their own PABA. Sulfonamide drugs are structurally similar to PABA, and their antibacterial activity is due to their ability to interfere with the conversion of PABA to folate by the enzyme dihydropteroate synthetase. Thus, bacterial growth is limited through folate deficiency.
Sources: en.wikipedia.org
它属于合成修饰肽，同时激动 GIP 与 GLP-1 两种肠促胰素受体。这类分子通常被称为双重肠促胰素受体激动剂，与选择性 GLP-1 激动剂在靶点范围上不同。
分子上的脂肪酸侧链使其与血浆白蛋白结合增强，显著延长循环半衰期。半衰期延长后，稳定血药浓度可在较长的给药间隔内维持，因此常见用法为每周一次。
同时激活两条肠促胰素通路可能在胰岛素分泌、胃排空和食欲调节上产生叠加效应。与单靶点相比，临床研究中观察到的血糖与体重变化幅度通常更明显，但各通路的具体贡献比例尚无定论。
It is a synthetic peptide and a dual agonist of two incretin receptors. It is not a small molecule, and it is not structurally related to the older single-receptor peptide agonists.