Everything below concerns Incretin. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2025-11-13. Where a claim depends on a specific study, the study is described rather than over-claimed.
Tirzepatide activates both the glucose-dependent insulinotropic polypeptide receptor and the glucagon-like peptide-1 receptor, making it a dual agonist rather than a selective agent. Engagement of the GLP-1 receptor is linked to glucose-dependent insulin release, slower gastric emptying, and reduced appetite signalling. The relative contribution of the GIP arm remains an active research question; proposed roles include improved insulin sensitivity and altered adipose tissue handling. Receptor occupancy studies suggest the molecule interacts with both targets at circulating concentrations achieved during therapy.
Development began in the 2010s, when researchers modified a GIP-based scaffold to add GLP-1 activity and then attached the fatty diacid to lengthen its half-life. Clinical evaluation proceeded through large phase 3 programmes in type 2 diabetes and in obesity, and regulators in the United States cleared the compound for type 2 diabetes in 2022 and for chronic weight management in 2023. Several cardiovascular and metabolic outcome studies are still reporting, so the picture of long-term benefit and risk is incomplete. Approvals in other regions followed on different timelines.
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.
Development of tirzepatide took place under a research program that sought to test whether simultaneous engagement of two incretin receptors would produce greater metabolic effects than single-receptor agonism. Clinical trials were organized into the SURPASS series for type 2 diabetes and the SURMOUNT series for obesity and weight management. Regulatory clearance for type 2 diabetes came in 2022 in the United States, followed by approval for chronic weight management in 2023. The trial programs reported reductions in glycated hemoglobin and body weight relative to comparators, though long-term cardiovascular and durability data continue to accumulate.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C225H348N48O68 | Peptide backbone with a fatty diacid chain |
| Molecular weight | About 4813 Da | Calculated from the formula |
| Receptor targets | GIP and GLP-1 receptors | Dual agonist activity at both sites |
| Route of administration | Subcutaneous injection | No approved oral form at present |
| Elimination half-life | About 5 days | Supports extended intervals between administrations |
溶解操作一般使用注射用水或适宜的水性缓冲液，必要时加入少量助溶剂以改善溶解速度，但应避免剧烈涡旋振荡，因为剪切力可能促进聚集。配制后的溶液在冷藏条件下的稳定时间通常短于固体形态，具体时限取决于浓度、缓冲体系与容器材质。是否加入防腐成分，则取决于用途是否为多次取样。
定量分析的主流方法是反相高效液相色谱联用紫外或质谱检测，利用肽在疏水固定相上的保留行为确定纯度与含量。对于生物基质中的浓度测定，常采用液相色谱串联质谱，并配合固相萃取或蛋白沉淀进行样品前处理。免疫分析法也可使用，但可能受到结构相关肽的交叉反应干扰。
In clinical research, tirzepatide has been studied in randomized controlled trials for glycemic control and body weight reduction. These trials typically measure changes in hemoglobin A1c and body weight over periods of several months. The drug is administered by subcutaneous injection, and its pharmacokinetic profile supports once-weekly dosing. Post-marketing surveillance continues to evaluate long-term outcomes and rare adverse events.
Tirzepatide is a synthetic peptide that acts as a dual agonist at the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. The molecule contains 39 amino acids and features a C20 fatty diacid moiety attached via a linker, which promotes albumin binding and extends its circulating half-life. Its sequence incorporates non-natural amino acids and modifications that reduce susceptibility to degradation by dipeptidyl peptidase-4. This dual receptor activity distinguishes it from selective GLP-1 receptor agonists.
The GIP receptor is expressed in pancreatic islets, adipose tissue, and the central nervous system, while GLP-1 receptors are found in pancreatic islets, the gastrointestinal tract, and the brain. Activation of both receptors can enhance glucose-dependent insulin secretion and reduce glucagon release. The relative contribution of each receptor to the overall pharmacological effect remains an area of ongoing investigation. Preclinical studies suggest that GIP receptor agonism may modulate appetite and energy balance, but the precise mechanisms in humans are not fully established.
Their feature documentary Kumu Hina, about transgender native Hawaiian teacher and cultural icon Hinaleimoana Wong-Kalu, was supported by ITVS, Pacific Islanders in Communications and the Ford Foundation and won the GLAAD Media Award for Outstanding Documentary and the Independent Lens Audience Award on PBS In 2017, Hamer and Wilson, with Hinaleimoana Wong-Kalu as producer, released Leitis in Waiting and Lady Eva, which documented the lives of transgender women in the conservative South Pacific Kingdom of Tonga. This was followed in 2019 by The Rogers, about transgender men in Samoa. These films became part of a campaign to decriminalize same-sex relationships across the Pacific. Hamer, Wilson and Wong-Kalu continued their collaboration in 2020 with the animated short film Kapaemahu, based on the hidden history of four stones on Waikiki Beach placed there as a tribute to four legendary mahu who first brought the healing arts from Tahiti to Hawaii. It premiered and won the Special Jury Prize at the Tribeca Film Festival and was shortlisted for an Oscar as Best Animated Short Film at the 93rd Academy Awards. The animated film was followed by a children's book published by Kokila, a PBS feature documentary, a multimedia exhibition at the Bishop Museum, permanent display at the Hawaiʻi Convention center, and inclusion in new interpretative signage at the Kapaemahu monument in Waikiki. The team's most recent film is Aikane, an animated short based on the Hawaiian term for intimate friends of the same sex.
In December 2022, the British government announced that it planned to open the Independent Inquiry relating to Afghanistan to investigate extrajudicial killings that took place between 2010 and 2013, during the War in Afghanistan. This followed a detailed BBC Panorama investigation that found members of the SAS "repeatedly killed detainees and unarmed men in suspicious circumstances". Panorama spoke to witnesses who alleged that operatives justified the killings of unarmed persons by leaving weapons at the scenes of the shootings and that SAS squadrons competed '"with each other to get the most kills". According to the investigation, officers of the UK Special Forces were concerned over the number of reports of detainees being killed after reaching for hidden weapons. Allegedly, several raids ended with the deaths of more people than weapons recovered. The BBC visited the sites of some raids and heard from ballistics experts who interpreted the bullet patterns present as more indicative "of execution-style killings rather than firefights". A formal internal review was opened at the time, but evidence was never passed to military police. The inquiry was launched in March 2023, to be chaired by Lord Justice Haddon-Cave. In September 2024, an internal Ministry of Defence document written in 2019 was presented to the inquiry that concluded that the BBC Panorama allegations were "broadly accurate".
=== Risk of forgoing conventional medical care === As with other alternative medicines, unethical or naïve practitioners may induce patients to exhaust financial resources by pursuing ineffective treatment. Professional ethics codes set by accrediting organizations such as the National Certification Commission for Acupuncture and Oriental Medicine require practitioners to make "timely referrals to other health care professionals as may be appropriate." Stephen Barrett states that there is a "risk that an acupuncturist whose approach to diagnosis is not based on scientific concepts will fail to diagnose a dangerous condition".
Circular necrosis of the white matter in the periphery of the spinal cord was also noted which probably resulted from circulatory disturbance secondary to tumor infiltration. Dorsal radiculopathy which is secondary ascending degeneration of the posterior funiculus may also occur due to malignant cells collecting or a presence of tumor which cause compression of the nerve. Tumor cell proliferation is observed around nerve roots as well as loss of myelinated nerve fibers and axonal swelling. In areas of tumor cells, infiltration of macrophages is observed. Nerve root infiltration has shown positive correlation with meningeal dissemination. Infiltration of the spinal cord parenchyma is found with destruction of the pia mater. Tumor cell infiltration is associated with spongy changes in the white matter of the spinal cord beneath the pia mater with demyelination, axonal swelling, and macrophage infiltration. Transverse necrosis of the spinal cord is usually marked with bleeding from tumor growth in the subarachnoid space and is the result of compression by the hematoma in the subarachnoid space.
=== Genetics === In MCTD, major histocompatibility complex (MHC) and non-MHC genes have been linked to disease vulnerability. HLA-DR4 in the MHC is linked to both anti-RNP antibody responses and MCTD. The HLA class II phenotype/genotype most closely connected with scleroderma, HLA-DR5, and its subgroups, has been demonstrated to have a negative connection with MCTD. Another genetic feature of MCTD is the presence of anti-RNP antibodies. However, these antibodies are not present in all patients. Genome-wide association studies have revealed that there are parts of a patient’s genetic material that cause production of these anti-RNP antibodies. The mechanism is not yet thoroughly defined.
Sources: en.wikipedia.org
tarnish A thin layer of corrosion that forms on the surface of copper, brass, aluminum, magnesium, and other soft metals or alloys as their outermost layer undergoes a chemical reaction with the surrounding air, often but not necessarily involving atmospheric oxygen. Tarnish usually appears as a dull grey, black, or sometimes iridescent film or coating on the metal. It is a self-limiting surface phenomenon, as the tarnished top layers of the metal protect underlying layers from reacting.
Enzyme inhibitors are molecules that reduce or abolish enzyme activity, while enzyme activators are molecules that increase the catalytic rate of enzymes. These interactions can be either reversible (i.e., removal of the inhibitor restores enzyme activity) or irreversible (i.e., the inhibitor permanently inactivates the enzyme).
The most recently named elements – nihonium (113), moscovium (115), tennessine (117), and oganesson (118) – completed the seventh row of the periodic table. Future elements would have to begin an eighth row. These elements may be referred to either by their atomic numbers (e.g. "element 164"), or by the IUPAC systematic element names adopted in 1978, which directly relate to the atomic numbers (e.g. "unhexquadium" for element 164, derived from Latin unus "one", Greek hexa "six", Latin quadra "four", and the traditional -ium suffix for metallic elements). All attempts to synthesize such elements have failed so far. Attempts to make element 119 have been ongoing since 2018 at the Riken research institute in Japan and since 2026 at the JINR in Russia, and an attempt to make element 120 has been ongoing since 2025 at the LBNL in the United States. The Heavy Ion Research Facility in Lanzhou (HIRFL) in China also plans to make its own attempts at synthesizing the first few period 8 elements. If the eighth period followed the pattern set by the earlier periods, then it would contain fifty elements, filling the 8s, 5g, 6f, 7d, and finally 8p subshells in that order. But by this point, relativistic effects should result in significant deviations from the Madelung rule. Various different models have been suggested for the configurations of eighth-period elements, as well as how to show the results in a periodic table. All agree that the eighth period should begin like the previous ones with two 8s elements, 119 and 120.
==== Mental fitness ==== Mental fitness is a mental health movement that encourages people to intentionally regulate and maintain their emotional wellbeing through friendship, regular human contact, and activities that include meditation, calming exercises, aerobic exercise, mindfulness, having a routine and maintaining adequate sleep. Mental fitness is intended to build resilience against every-day mental and potentially physical health challenges to prevent an escalation of anxiety, depression, and suicidal ideation. This can help people, including older adults with health challenges, to more effectively cope with the escalation of those feelings if they occur.
== Release history == Reek of Putrefaction was first released in 1988. When released, Reek of Putrefaction reached No. 6 on the UK Indie Chart, establishing Carcass' earlier grindcore sound. The late BBC Radio 1 DJ John Peel declared it his favourite album of 1988, in an interview for British newspaper The Observer. Reek of Putrefaction was re-released in 1994. In 2002, the album was reissued. The album was re-released in 2008 as part of an ongoing series of Carcass reissues to tie in with their reunion. The main album, along with the demo Flesh Ripping Sonic Torment, is presented as one side of a dualdisc, while the DVD side features the first part of an extended documentary titled The Pathologist's Report Part I: Incubation. Later editions contain the album on a CD and the documentary on a separate DVD. The album is presented in a 12-panel digipak with full lyrics and artwork and is sealed in a white medical bag with sticker, to hide the controversial cover art.
Sources: en.wikipedia.org
== Historical significance == Dr. Luis Leloir deduced the role of GALE in galactose metabolism during his tenure at the Instituto de Investigaciones Bioquímicas del Fundación Campomar, initially terming the enzyme waldenase. Dr. Leloir was awarded the 1970 Nobel Prize in Chemistry for his discovery of sugar nucleotides and their role in the biosynthesis of carbohydrates.
== DeSUMOylation == SUMO can be removed from its substrate, which is called deSUMOylation. Specific proteases mediate this procedure (SENP in human or Ulp1 and Ulp2 in yeast). In yeast, SMT3 encodes the SUMO protein, and SUMO E3 ligase attaches SUMO to target proteins. In cell cycle regulation, the base case is that SUMO ligation is constantly taking place, leading to polySUMOylation of eligible target proteins. This is countered by the SUMO protease Ulp2 which cleaves polySUMO groups, leaving the protein in a monoSUMOylated state. As shown in the figure, there is a feedback mechanism in which ULP2 maintains the monoSUMOylated state by passively and diligently cleaving SUMO such that the polySUMOylated state is never stabilized enough to be acted upon by downstream actors. This deSUMOylation is critical to prevent precocious advancement of the cell cycle as discussed in several studies.
It would therefore appear desirable to process a material in such a way that it is physically uniform with regard to the distribution of components and porosity, rather than using particle size distributions which will maximize the green density. The containment of a uniformly dispersed assembly of strongly interacting particles in suspension requires total control over particle-particle interactions. A number of dispersants such as ammonium citrate (aqueous) and imidazoline or oleyl alcohol (nonaqueous) are promising solutions as possible additives for enhanced dispersion and deagglomeration. Monodisperse nanoparticles and colloids provide this potential. Monodisperse powders of colloidal silica, for example, may therefore be stabilized sufficiently to ensure a high degree of order in the colloidal crystal or polycrystalline colloidal solid which results from aggregation. The degree of order appears to be limited by the time and space allowed for longer-range correlations to be established. Such defective polycrystalline colloidal structures would appear to be the basic elements of sub-micrometer colloidal materials science, and, therefore, provide the first step in developing a more rigorous understanding of the mechanisms involved in microstructural evolution in high performance materials and components.
=== Mi === August Michaelis (1847–1916), German chemist who discovered the Michaelis–Arbuzov reaction Leonor Michaelis (1875–1949), German biochemist and physical chemist known for fundamental advances in enzyme chemistry Hartmut Michel (born 1948), German biochemist, 1988 Nobel Prize in Chemistry for determination of the first crystal structure of an integral membrane protein Huang Minlon (1889–1979), Chinese chemist, pioneer of modern pharmaceutical industries in China Stanley Miller (1930–2007), American chemist, best known for the Miller–Urey experiment Eugène Millon (1812–1867), French military chemist and physician who discovered the reaction of mercury and nitric acid with egg albumen David P. Mills (PhD 2007), British chemist who investigates lanthanide and actinide f-block elements Luis E. Miramontes (1925–2004), Mexican co-inventor of the combined oral contraceptive pill Peter D. Mitchell (1920–1992), British biochemist known for the theory of chemiosmosis, 1978 Nobel Prize in Chemistry Eilhardt Mitscherlich (1794–1863), German chemist, remembered for the law of isomorphism. Alexander Mitscherlich (1836–1918), German chemist known for discovering crystallographic isomorphism
=== Prevention of suicide === Lithium has been shown to reduce the risk of suicide in individuals with bipolar disorder or major depression to close to the same level as that of the general population. It is thought to exert this effect by treating the underlying mood disorder and through a reduction in impulsivity and aggressiveness. Lithium is proven to reduce the risk of suicide in mood disorders by 87% in randomized double-blind placebo-controlled trials. Some meta-analyses have not found a statistically significant association between lithium and a reduction in suicide, however these meta-analyses are disputed. Some evidence suggests lithium is effective in significantly reducing the risk of self-harm and unintentional injury for bipolar disorder in comparison to no treatment and to antipsychotics or valproate. In addition, lithium decreases all-cause mortality in people with bipolar disorder. The increased presence of trace amounts of lithium in drinking water is correlated with lower overall suicide rates, especially among men. Lithium in drinking water is also associated with lower rates of homicide, rape, drug arrests, and other crimes.
Sources: en.wikipedia.org
It is a synthetic 39-amino-acid peptide that acts on two incretin receptors, the GIP receptor and the GLP-1 receptor. It is given by subcutaneous injection and has a circulating half-life of roughly five days. It is not a small molecule and is not absorbed usefully from the gut in conventional oral form.
Selective agents act on one receptor, while tirzepatide engages both GIP and GLP-1 receptors. The added GIP activity may contribute effects on insulin sensitivity and on fat metabolism. Whether the dual action produces meaningful clinical advantages beyond differences in potency is still being examined.
The downstream consequences of GIP receptor activation are not fully characterised in humans. It is also unclear how much each receptor contributes to appetite reduction and to shifts in body composition. Published work describes associations and proposed pathways rather than settled causal chains.
It binds and activates both the GIP and GLP-1 receptors, making it a dual incretin receptor agonist. Single-receptor GLP-1 agonists act on one target only. The dual profile is the defining pharmacological feature of the molecule.