A practical reference on 双受体激动: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
This page was last updated on 2025-11-14 and is reviewed periodically as new material appears.
Tirzepatide is a synthetic linear peptide of 39 amino acids that acts as a dual agonist at the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. Its sequence derives from native GIP but incorporates non-natural residues and a C20 fatty diacid moiety linked to a lysine side chain. The lipophilic chain promotes albumin binding, which slows renal clearance and extends circulation time. The unmodified peptide has a molecular formula of C225H348N48O68 and a molecular mass near 4,813 daltons.
Receptor activation by tirzepatide raises intracellular cyclic AMP through Gs-coupled signalling at both targets. At the GLP-1 receptor the downstream effect includes glucose-dependent insulin release, suppressed glucagon secretion, delayed gastric emptying, and reduced appetite signalling in the hypothalamus. GIP receptor engagement adds insulinotropic activity and appears to influence lipid handling in adipose tissue. Because both receptors are stimulated at the same time, the pharmacological profile differs from that of selective GLP-1 receptor agonists, and the relative contribution of each arm remains an area of active investigation.
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。
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C225H348N48O68 | Unmodified peptide backbone |
| Molecular mass | approx. 4,813 Da | 39-residue linear chain |
| Receptor targets | GIP and GLP-1 | Dual agonist activity |
| Route | Subcutaneous injection | Weekly administration interval |
| Elimination half-life | approx. 5 days | Supports weekly dosing schedule |
Tirzepatide is a synthetic peptide built from 39 amino acid residues. Its backbone derives from the native glucose-dependent insulinotropic polypeptide sequence, altered at several positions to resist enzymatic cleavage. A fatty diacid group attached through a linker extends plasma residence time by promoting reversible binding to serum albumin. The molecule carries a net negative charge near physiological pH and has a reported molecular weight close to 4813 daltons. These features separate it from shorter incretin analogs and account for its prolonged dosing interval.
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.
The peptide activates two G protein-coupled receptors, GIPR and GLP-1R. Binding triggers adenylyl cyclase activity and raises intracellular cyclic AMP in pancreatic beta cells, which potentiates insulin release when glucose is elevated. Signaling in the central nervous system is associated with reduced appetite and lower energy intake, while effects on gastric emptying and glucagon secretion are also reported. Because activity at both receptors is retained, the pharmacological profile is often described as incretin-based rather than selective for a single receptor.
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.
==== Post-treatment isolation ==== Ablation doses are usually administered on an inpatient basis, and IAEA International Basic Safety Standards recommend that patients are not discharged until the activity falls below 1100 MBq. ICRP advice states that "comforters and carers" of patients undergoing radionuclide therapy should be treated as members of the public for dose constraint purposes and any restrictions on the patient should be designed based on this principle. Patients receiving I-131 radioiodine treatment may be warned not to have sexual intercourse for one month (or shorter, depending on dose given), and women told not to become pregnant for six months afterwards. "This is because a theoretical risk to a developing fetus exists, even though the amount of radioactivity retained may be small and there is no medical proof of an actual risk from radioiodine treatment. Such a precaution would essentially eliminate direct fetal exposure to radioactivity and markedly reduce the possibility of conception with sperm that might theoretically have been damaged by exposure to radioiodine." These guidelines vary from hospital to hospital and will depend on national legislation and guidance, as well as the dose of radiation given. Some also advise not to hug or hold children when the radiation is still high, and a one- or two- metre distance to others may be recommended. I-131 will be eliminated from the body over the next several weeks after it is given.
Taha Othman Ishaq (or Osman), a lawyer and member of the FFC negotiating committee, declined his nomination by the FFC to the Sovereignty Council on the grounds that the FFC alliance had earlier agreed that members of the negotiating committee should not become members of the Sovereignty Council. Raja Nicola was the civilian member of the Sovereignty Council mutually chosen by the FFC and TMC. The choice of Nicola, as a member of the Sudanese Copt community, is seen as a symbol of respect for diversity, in particular to Sudanese Christians. On 4 February 2021, al-Burhan issued a decree to add three new members to the Council. The new members are Sudanese Revolutionary Front leader El Hadi Idris Yahya, Sudan People's Liberation Movement-North leader Malik Agar, and Sudan Liberation Movement for Justice-Karbino leader El Tahrir Abubakr Hajar.
=== Quantum dots === Graphene quantum dots (GQDs) keep all dimensions less than 10 nm. Their size and edge crystallography govern their electrical, magnetic, optical, and chemical properties. GQDs can be produced via graphite nanotomy or via bottom-up, solution-based routes (Diels-Alder, cyclotrimerization and/or cyclodehydrogenation reactions). GQDs with controlled structure can be incorporated into applications in electronics, optoelectronics and electromagnetics. Quantum confinement can be created by changing the width of graphene nanoribbons (GNRs) at selected points along the ribbon. It is studied as a catalyst for fuel cells.
Sources: en.wikipedia.org
The average stretched penile length at birth is about 4 cm (1.6 in), and the length for 90% of newborn boys is between 2.4 and 5.5 cm (0.94 and 2.17 in). Limited growth of the penis occurs between birth and 5 years of age, but very little occurs between 5 years and the onset of puberty. The average size at the beginning of puberty is 6 cm (2.4 in), with adult size reached about 5 years later. W. A. Schonfeld published a penis growth curve in 1943.
They also included giving the Reserve Forces and Cadets Associations the power to produce an annual report to Parliament on the state of the volunteer reserves (the Royal Naval Reserve, The Royal Marines Reserve, the Army Reserve and the Royal Auxiliary Air Force). In January 2021, the Army Reserve trained strength stood at 26,820. (This figure excludes recruits undergoing phase 1 training and various non-deployable categories such as University Officers' Training Corps). During 2020, three reserve infantry battalions, 7 Rifles and 5 Fusiliers followed by 6 Rifles, provided the framework battalion for peacekeeping in Cyprus and over the winter 20/21 the Royal Yeomanry provided a composite squadron for a six-month tour on armoured reconnaissance as part of Britain's forward presence in Estonia. Army Reservists have a minimum commitment to serve 27 training days per year or 19 days for some national units. This period normally includes a two-week period of continuous training either as an Army Reserve unit, on courses or attached to a Regular unit. Army Reserve soldiers are paid at a similar rate to their regular equivalents while engaged on military activities.
== Classification == Described primarily based on the type of biochemical group transferred, transferases can be divided into ten categories (based on the EC Number classification). These categories comprise over 450 different unique enzymes. In the EC numbering system, transferases have been given a classification of EC2. Hydrogen is not considered a functional group when it comes to transferase targets; instead, hydrogen transfer is included under oxidoreductases, due to electron transfer considerations.
Sources: en.wikipedia.org
== End-of-use == Plastic: Landfilling, burning, and recycling are all alternatives for plastic packaging at the end of their shelf-life. However, improper disposal and handling lead to higher percentages of plastic waste, which can pollute the environment in a wide spectrum of scenarios. The packaging sector accounts for 40.5% of all plastic produced in Europe, which represents the largest sector in food industry. However, the recycling of such wastege is at a critical low level of roughly 35%. Moreover, it has been estimated that over 20% of the plastic packaging does not reach any recycling process. Bioplastic: also known as biodegradable polymer or biopolymer, are usually made from renewable feedstock resources like corn, potatoes, wood pulp and sugarcane, as well as from renewable natural resources of different kind. Typical end-of-life options include the composting or the environmental degradation of bioplastics, which result in resource loss and CO2 production. Complete degradation is also only achievable under rigorous conditions that are infrequently offered by the company. Additionally, some bioplastics are processed similarly to their traditional, fossil-based counterparts, which, if improperly sorted, might cause harmful interferences in other materials' recycling processes. Paper, paperboard, and corrugated board: are composed of cellulosic fibers bonded together to form a flexible structure.
== Nutrition == Sake kasu is a highly nutritious by-product of sake providing protein, carbohydrates, fat, vitamins (including some B vitamins), fiber, ash, peptides, and amino acids. It has also been found that sake kasu has the potential to reduce the risk of non-alcoholic fatty liver disease (NAFLD) and an extract has potential to be used as a treatment. According to a science television program, "Tameshite Gatten", that aired on NHK in Japan, it was explained that the fiber and resistant protein in sake kasu can reduce low-density lipoprotein cholesterol levels and amino acids. Whether sake kasu is heat-dried or freeze-dried, there is little difference in nutritional value between the two drying methods. With heat-dried sake kasu there are more free amino acids, whereas the freeze-dried sake kasu contains more S-adenosyl methionine. The degradation of microbial metabolites during heat-drying sake kasu can cause an increase in the amount of nucleic acid-related components. When feeding aging mice with sake kasu, the branched-chain amino acid level is high in different parts of the mice including the plasma, brain, and muscle. Based on the experiment, it is believed that consuming sake kasu may be beneficial towards the elderly in maintaining brain tissue and motor functions. Fermented sake kasu is produced by introducing lactic acid bacteria to the sake kasu during the fermentation process. Consuming fermented sake kasu can suppress type I allergic reaction and allergic rhinitis-like symptoms.
Digital Audio Broadcasting (DAB) debuted in some countries in 1998. It transmits audio as a digital signal rather than an analog signal as AM and FM do. DAB has the potential to provide higher quality sound than FM (although many stations do not choose to transmit at such high quality), has greater immunity to radio noise and interference, makes better use of scarce radio spectrum bandwidth and provides advanced user features such as electronic program guides. Its disadvantage is that it is incompatible with previous radios so that a new DAB receiver must be purchased. Several nations have set dates to switch off analog FM networks in favor of DAB / DAB+, notably Norway in 2017 and Switzerland in 2024. A single DAB station transmits a 1,500 kHz bandwidth signal that carries from 9–12 channels of digital audio modulated by OFDM from which the listener can choose. Broadcasters can transmit a channel at a range of different bit rates, so different channels can have different audio quality. In different countries DAB stations broadcast in either Band III (174–240 MHz) or L band (1.452–1.492 GHz) in the UHF range, so like FM reception is limited by the visual horizon to about 40 miles (64 km). HD Radio is an alternative digital radio standard widely implemented in North America. An in-band on-channel technology, HD Radio broadcasts a digital signal in a subcarrier of a station's analog FM or AM signal. Stations are able to multicast more than one audio signal in the subcarrier, supporting the transmission of multiple audio services at varying bitrates.
Attachment to the neck dam is critical to diver safety and a reliable locking mechanism is needed to ensure that it is not inadvertently released during a dive. When using a dry suit, the neck dam may be permanently omitted and the lower part of the helmet assembly attached directly to the suit. The term "Lightweight" is relative; the helmets are only light in comparison with the old copper hats. They are supported only by the head and neck of the diver, and are uncomfortably heavy (Weight of KM 77 = 32.43 pounds) out of the water, as they must be ballasted for neutral buoyancy during the dive, so they don't tend to lift the diver's head with excess buoyancy. There is little difference in weight between the metal shell and GRP shell helmets because of this ballasting, and the weight is directly proportional to the total volume - smaller helmets are lighter. To avoid fatigue, divers avoid donning the helmet until just prior to entering the water. Having the helmet supported by the head has the advantage that the diver can turn the helmet to face the job without having to turn the entire upper torso. This is particularly an advantage when looking upwards. This allows the helmet to have a relatively small faceplate, which reduces overall volume and hence the weight. Demand breathing systems reduce the amount of gas required to adequately ventilate the diver, as it needs only to be supplied when the diver inhales, but the slightly increased work of breathing caused by this system is a disadvantage at extreme levels of exertion, where free-flow systems may be better.
Sources: en.wikipedia.org
It is a dual GIP and GLP-1 receptor agonist, frequently grouped with incretin-based peptide therapeutics. It is a peptide rather than a small molecule and is given by subcutaneous injection.
Selective agents engage only the GLP-1 receptor, whereas tirzepatide activates GIP and GLP-1 receptors simultaneously. This difference in receptor coverage is the principal pharmacological distinction emphasised in comparative reviews.
Downstream signalling is partly characterised, but the quantitative contribution of GIP versus GLP-1 receptor activation to metabolic outcomes is not settled. Review articles commonly flag this as an unresolved question rather than a settled finding.
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。