This is a working overview of glucagon receptor, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2025-12-17 and is reviewed periodically as new material appears.
与仅靶向单一受体的同类药物相比，瑞他鲁肽增加胰高血糖素受体成分，理论上可提高能量消耗并改变脂肪分布。临床中观察到的体重变化是否主要来自该额外机制，目前尚无定论。胃肠道反应是该类药物常见不良事件，试验中通过剂量递增和监测进行管理。停药后体重反弹、个体差异和长期耐受性仍需更多数据。
瑞他鲁肽是一种在研合成肽，同时作用于胰高血糖素样肽-1、葡萄糖依赖性促胰岛素多肽和胰高血糖素受体。该分子属于多受体激动剂类别，尚未获得任何监管机构的上市批准。当前临床开发主要针对肥胖和2型糖尿病，研究代号为LY3437943。已确立的信息包括受体靶点和部分中期试验结果；最终疗效、长期安全性和适用人群仍属开放问题。
开发进程从早期单次和多次给药研究推进至大规模后期试验。公开报告显示，参与者在体重和相关代谢指标上出现变化，但完整数据需经同行评审并接受独立复核。试验设计通常包括随机、双盲和对照设置，以区分药物效应与行为干预。监管提交和标签范围尚未确定；长期维持效果与心血管结局仍是开放问题。
Receptor activation produces downstream effects that differ by tissue. GLP-1 receptor signaling influences appetite regulation and insulin secretion in a glucose-dependent manner. GIP receptor activity contributes to metabolic handling of nutrients and may modulate adipose tissue. Glucagon receptor engagement raises energy expenditure and promotes hepatic lipid turnover, though the balance among these actions in humans is still being characterized. Preclinical models showed reductions in body weight and improved glycemic markers.
Clinical development has progressed through phase 2 trials in adults with obesity and type 2 diabetes, with phase 3 programs reported as ongoing. Reported outcomes include reductions in body weight and improvements in glycemic measures over defined treatment periods. Whether these effects translate into durable benefits after treatment ends remains an open question. Long-term safety data across broad populations are not yet complete, and regulatory decisions have not been announced.
Retatrutide is an investigational synthetic peptide engineered to activate three distinct hormone receptors within a single molecule. It targets the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor, and the glucagon receptor simultaneously. This triagonist design distinguishes it from earlier incretin-based compounds that act on one or two of these pathways. Structural modifications relative to native gut hormones extend its residence time in circulation. The molecule remains under clinical evaluation and is not approved for any indication.
| Property | Value | Notes |
|---|---|---|
| 研究代号 | LY3437943 | 文献中常用的实验标识 |
| 药物类别 | 三重受体激动剂 | 靶向GLP-1、GIP与胰高血糖素受体 |
| 开发状态 | 后期临床研究 | 尚未获批上市 |
| 主要研究人群 | 肥胖与2型糖尿病 | 入组条件依试验方案而定 |
| 常见同义词 | 瑞他鲁肽；LY3437943 | 名称拼写可能因语言和出版物而异 |
Several questions about the compound remain unresolved. The durability of weight reduction after treatment stops, the frequency of gastrointestinal side effects, and the long-term cardiovascular profile are topics of ongoing study. Regulatory submissions and phase 3 trial outcomes have not been fully reported in the public literature. Because most available data come from controlled trials rather than general-population use, conclusions about effectiveness outside study settings are provisional. The distinction between established findings and open questions matters when interpreting early coverage of the drug.
Retatrutide is an investigational peptide developed by a pharmaceutical company as a multi-receptor agonist for treating obesity and type 2 diabetes. The compound emerged from research into gut-hormone analogues that act on several receptors simultaneously rather than on a single target. Early preclinical work examined how combined activity at three distinct receptors might produce greater metabolic effects than single-receptor compounds. Published phase 2 results have described substantial reductions in body weight among participants, although the compound remains unapproved in most jurisdictions as of the mid-2020s.
Pharmacologically the compound activates three receptors: GLP-1, GIP, and glucagon. GLP-1 and GIP signaling contribute to glucose-dependent insulin release, delayed gastric emptying, and reduced appetite, while glucagon receptor activation is associated with increased energy expenditure and hepatic fat oxidation. The single-molecule design is intended to keep these activities in one peptide rather than combining separate agents. Relative activity at each receptor differs, and the balance between them is a central question in interpretation. The glucagon component is partly offset by incretin-mediated insulin secretion, an interaction that remains incompletely characterized.
Development has progressed from single- and multiple-ascending-dose studies in healthy volunteers into larger randomized trials in adults with obesity, type 2 diabetes, and fatty liver disease. Early reports describe dose-dependent reductions in body weight and improvements in glycemic markers over treatment periods of several months. Whether the glucagon arm adds tolerability cost without added benefit is still debated. Long-term cardiovascular outcomes, effects after treatment stops, and performance in older or comorbid populations are open questions rather than settled findings. Approval status may change, so the current investigational label should be confirmed against regulatory sources.
Development has progressed through early- and mid-stage human studies in adults with obesity and with type 2 diabetes. Published phase 2 data reported reductions in body weight and improvements in glycemic markers over the treatment period. No regulatory agency has approved the compound for any indication, and it remains available only within controlled research settings. Whether benefits observed in trials translate into durable outcomes after treatment stops is not yet established.
Retatrutide is an investigational synthetic peptide that acts as an agonist at three distinct G protein-coupled receptors. It combines activity at the glucagon-like peptide-1 receptor, the glucose-dependent insulinotropic polypeptide receptor, and the glucagon receptor within a single molecule. This multi-receptor profile distinguishes it from earlier incretin-based compounds that engage one or two of these pathways. Researchers designed the molecule to test whether simultaneous activation produces greater metabolic effects than single or dual agonism alone.
The intended pharmacology combines three signals in one molecule. GLP-1 receptor activation reduces appetite and slows gastric emptying, effects already exploited by approved incretin-based therapies. GIP receptor engagement is associated with improved insulin sensitivity and with direct effects on adipose tissue, although how much it contributes to overall outcomes is still debated. Glucagon receptor agonism raises energy expenditure and supports hepatic lipid handling, a mechanism that also tends to increase glucose output. The triple profile is hypothesized to produce a larger metabolic effect than single or dual agonism, but the relative weight of each receptor in humans is not settled.
Human evidence remains limited to controlled studies. A phase 2 trial in adults with obesity reported large, dose-dependent reductions in body weight over 48 weeks, with gastrointestinal events as the most frequently recorded adverse effect. Phase 3 programs designated TRIUMPH, for obesity, and TRANSCEND, for type 2 diabetes, are intended to confirm efficacy and to characterize safety in larger populations. Related studies are examining conditions such as knee osteoarthritis in people with obesity and metabolic liver disease. Open questions include long-term tolerability, effects on lean mass, and what happens after treatment is stopped.
According to PROLADES, Belize's population was 64.6% Catholic, 27.8% Protestant, and 7.6% of other faiths in 1971. Until the late 1990s, Belize was a Catholic-majority country. Catholics formed 57% of the population in 1991, a share that dropped to 49% in 2000. The percentage of Catholics in the population has been decreasing in the past few decades due to the growth of Protestant churches, other religions and irreligiosity. In addition to Catholics, there has always been a large accompanying Protestant minority. It was brought by British, German, and other settlers to the British colony of British Honduras. From the beginning, it was largely Anglican and Mennonite in nature. The Protestant community in Belize experienced a large Pentecostal and Seventh-Day Adventist influx tied to the recent spread of various Evangelical Protestant denominations throughout Latin America and neighboring regions. Geographically speaking, German Mennonites live mostly in the rural districts of Cayo and Orange Walk. The Greek Orthodox Church has a presence in Santa Elena. The Association of Religion Data Archives estimates there were 7,776 Baháʼís in Belize in 2005, or 2.5% of the national population. Their estimates suggest this is the highest proportion of Baháʼís in any country. Their data also states that the Baháʼí Faith is the second most common religion in Belize, following Christianity. Hinduism is followed by most Indian immigrants.
Most people with back pain do not experience chronic severe pain but rather persistent or intermittent pain that is mild or moderate. Still, chronic back pain symptoms, defined as repeated or persistent pain for at least 3 months within the past 12 months, affected 34.4% of a nationwide sample of adults in mild form, 25.1% in moderate form, and 13% in (very) severe form. In most cases of herniated disks and stenosis, rest, injections or surgery have similar general pain-resolution outcomes on average after one year. In the United States, acute low back pain is the fifth most common reason for physician visits and causes 40% of missed work days. It is the single leading cause of disability worldwide. According to the World Health Organization, approximately 90% of all low back pain cases are non-specific, meaning that no clear structural cause can be identified.
Secondary-ion mass spectrometry (SIMS) is a technique used to analyze the composition of solid surfaces and thin films by sputtering the surface of the specimen with a focused primary ion beam and collecting and analyzing ejected secondary ions. The mass/charge ratios of these secondary ions are measured with a mass spectrometer to determine the elemental, isotopic, or molecular composition of the surface to a depth of 1 to 2 nm. Due to the large variation in ionization probabilities among elements sputtered from different materials, comparison against well-calibrated standards is necessary to achieve accurate quantitative results. SIMS is the most sensitive elemental surface analysis technique, with elemental detection limits ranging from parts per million to parts per billion.
Magnetic refrigeration, or adiabatic demagnetization, is a cooling technology based on the magnetocaloric effect, an intrinsic property of magnetic solids. The refrigerant is often a paramagnetic salt, such as cerium magnesium nitrate. The active magnetic dipoles in this case are those of the electron shells of the paramagnetic atoms. A strong magnetic field is applied to the refrigerant, forcing its various magnetic dipoles to align and putting these degrees of freedom of the refrigerant into a state of lowered entropy. A heat sink then absorbs the heat released by the refrigerant due to its loss of entropy. Thermal contact with the heat sink is then broken so that the system is insulated, and the magnetic field is switched off. This increases the heat capacity of the refrigerant, thus decreasing its temperature below the temperature of the heat sink. Because few materials exhibit the needed properties at room temperature, applications have so far been limited to cryogenics and research.
Sources: en.wikipedia.org
Off California, white sharks will eat cabezons, white seabasses, lingcod, halibut, leopard sharks, smooth-hounds, spiny dogfishes, school sharks, stingrays, bat rays, and skates. In the Mediterranean, they consume Atlantic bluefin tunas, bullet tunas, Atlantic bonitos, swordfishes, blue sharks, shortfin makos, and stingrays. An ocean sunfish was also recorded in a white shark's stomach. Off the northeastern US, juveniles commonly eat bottom-dwelling fish like hake, while off South Africa, they often prey on dusky sharks. The remains of an adult whale shark were found in a white shark, though whether this was active hunting or scavenging could not be determined. They are also recorded to consume cephalopods, as evidenced by beaks found in their stomachs. Off South Africa, white sharks under 2.5 m (8.2 ft) were found with remains of coastal and bottom-dwelling species like certain octopus species, as well as species of the genera Sepia and Loligo, while larger sharks seem to prefer more open-ocean species like those of the genera Ancistrocheirus, Octopoteuthis, Lycoteuthis, Ornithoteuthis, Chiroteuthis, and Argonauta. Near Guadalupe, white sharks have been documented with scars that appear to have been caused by neon flying squids, jumbo squids, and giant squids. Both fish and cephalopods may be important food sources at the White Shark Café. Other animals recorded as prey include sea turtles.
In "Black Mesa Inbound", the player controls Gordon Freeman as he enters the facility on a monorail. After noticing the G-Man on a different train, Gordon departs and enters the Anomalous Materials Lab. He explores the area, donning his Hazardous Environment Suit, and then enters the test chamber. After the Anti-Mass Spectrometer power is turned up to 105%, the Resonance Cascade disaster occurs, and Freeman must escape the destroyed chamber. In "Unforeseen Consequences", Freeman returns to the Anomalous Materials Lab, fighting his way through the aliens that have started appearing from warps in space. He then makes his way through an office complex. In "We've Got Hostiles", Freeman encounters the Hazardous Environment Combat Unit (HECU), a special forces unit of the United States Marine Corps sent to cover up the disaster by killing all of the surviving Black Mesa personnel. He travels through a series of Cold War-era storage rooms to reach the surface. Escaping an Osprey helicopter, he goes back underground in a different location. In "Blast Pit", he must destroy an alien tentacle that has appeared from beneath a nuclear silo. After successfully destroying the tentacle with a rocket engine, in "Power Up", Freeman must kill a Gargantua alien by baiting it into a room with giant Tesla coils. He then navigates a series of underground rail tunnels in "On a Rail", culminating in the rocket launch of a satellite that can determine the scope of the disaster. In "Apprehension", Freeman fights through flooded rooms filled with aquatic aliens called Icthyosaurs.
In Indian culture, vegetarianism has been closely connected with the attitude of nonviolence towards animals (called ahimsa in India) for millennia and was promoted by religious groups and philosophers. The Ācārāṅga Sūtra from 5th century BCE advocates Jain-vegetarianism and forbids the monks from walking on grass in order to avoid inflicting pain on them and prevent small insects dwelling inside from getting killed. The ancient Indian work of the Tirukkuṟaḷ, dated before the 5th century CE, explicitly and unambiguously emphasizes shunning meat and non-killing as a common man's virtues. Chapter 26 of the Tirukkural, particularly couplets 251–260, deals exclusively on moral vegetarianism or veganism. Hemachandra, a 12th-century Jain scholar and monk, achieved a significant political victory for vegetarianism in Indian history. He successfully converted King Kumarapala of the Chaulukya dynasty (who ruled present-day Gujarat and surrounding areas) to Jainism. Under Hemachandra's guidance, King Kumarapala issued sweeping imperial edicts (amari-ghoshana) that legally banned the slaughter of animals across his entire kingdom. This alliance is historically responsible for cementing Gujarat as the geographic epicenter of strict vegetarian cuisine in India. In the 16th century, the Jain monk Hiravijaya Suri was invited to the court of the Mughal Emperor Akbar. Through philosophical discussions regarding nonviolence, the monk persuaded the Emperor to issue imperial edicts (farmans) that legally enforced animal welfare across the empire.
=== Coenzyme function === Vitamin B12 functions as a coenzyme, meaning that its presence is required in some enzyme-catalyzed reactions. Listed here are the three classes of enzymes that sometimes require B12 to function (in animals):
=== Life Expectancy After Starting Kidney Dialysis === Life expectancy after starting kidney dialysis for end-stage kidney disease (ESKD) varies significantly based on factors such as age, comorbidities, dialysis modality, and access to healthcare. Dialysis extends life compared to untreated ESKD but does not restore normal kidney function. Median survival is approximately 3–5 years, with 5-year survival rates around 35–42% for hemodialysis (HD) patients. Mortality is highest in the first year (15–20%), primarily from cardiovascular events or infections.
Sources: en.wikipedia.org
UIP pattern: Honeycombing, with or without peripheral traction bronchiectasis; or bronchiolectasis (dilatation of the terminal bronchioles) Predominantly subpleural and basal Often heterogenous distribution, being occasionally diffuse, and may be asymmetrical There may be superimposed CT features such as mild ground-glass opacity, reticular pattern and pulmonary ossification.
== Differences between countries == The sirloin steak is called the rump steak in British butchery. In common British, South African, and Australian butchery, sirloin refers to cuts of meat from the upper middle of the animal, similar to the American short loin, while the American sirloin is called the rump. These differences arise from butchery traditions and standard cutting systems, but can lead to confusion. For example, the T-bone steak is classified as part of the sirloin in British butchery, but as part of the short loin in American butchery.
Heated tobacco products were first introduced in 1988, but were not a commercial success. BLOW started selling e-hookahs, an electronic version of the hookah in 2014. The handle of each hose for the e-hookah contains a heating element and a liquid, which produces vapor. Gopal Bhatnagar, based in Toronto, Canada, invented a 3D printed adapter to turn a traditional hookah into an e-hookah. It is used instead of the ceramic bowl that contains shisha tobacco. Rather than the tobacco, users can insert e-cigarettes. Other non‑nicotine aerosol‑generating devices use technology similar to that of electronic cigarettes. Fog machines and haze machines, commonly used in entertainment venues, heat glycol‑based liquids to produce aerosols for visual effects. Industry standards organizations note that the droplets produced by theatrical fog and haze fall within the size range of particulate matter (PM2.5), a classification based on particle diameter. Recent research has shown that heating glycol‑based fluids in both fog and haze machines and electronic cigarettes can produce similar thermal degradation byproducts, including carbonyl compounds such as formaldehyde.
==== September ==== The Syrian Observatory for Human Rights reported that Firas Hamayel, a commander in the National Guard, was killed in an ambush in Suwayda. On 21 September, Ayoob Kara, former member of the Israeli Knesset, announced the independence of Suwayda, declaring "We proclaim September 21, 2025, as the historic day of Suwayda’s separation from Syria and from the terrorist government of Ahmed Al-Sharaa". On 26 September, the Syrian Druze militias established a local women's self-defense army as a response to the precarious security situation. More than 500 women are involved. Minors have been forcibly trained to use weapons. On 27 September, the Syrian transitional government bombed the city of Mecdel with a drone and also bombed the city of Kanaker.
Sources: en.wikipedia.org
尚未。它仍处于临床研究阶段，任何监管批准都取决于正在进行的试验结果和提交审评。可公开获取的信息以试验注册和会议摘要为主。
司美格鲁肽主要靶向GLP-1受体，而瑞他鲁肽同时作用于GLP-1、GIP和胰高血糖素受体。这种三重机制旨在产生不同的代谢效应，但临床差异仍需头对头研究确认。
长期心血管结局、停药后维持效果、罕见不良事件和不同人群中的获益风险比尚未完全确定。完整三期数据和监管审评将影响结论。
It is a synthetic peptide triagonist that engages GIP, GLP-1, and glucagon receptors. Investigational compounds in this class are studied for metabolic conditions rather than for a single organ system.