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What Is The Meaning Of Incretin?

Guideline For Incretin Measurement

Guideline For Incretin Measurement

With the launch of incretin agents, there will be an increased need for incretin (GIP and GLP1) concentration measurements in humans. The Japan Diabetes Society (JDS) and the Japan Association for Diabetes Education and Care (JADEC) have jointly formed the Committee on Standardized Incretin Measurement to address the relevant issues and develop recommendations for standardization of the measurement of incretin. At this time, the Committee has the following recommendations to facilitate evaluation and comparison of data that constitute the current Guideline for Incretin (GIP and GLP1) Measurement in Humans. The Committee will continue to review its recommendations as required and promulgate amendments to the Guideline on JDS and JADEC websites in a timely manner. Blood collection tubes containing a DPP4 inhibitor must be used in measuring levels of active incretin hormones. Blood samples must be stored on ice until separation of plasma, and then the separated plasma samples are stored at 20C. It is essential that plasma samples are extracted prior to measurement of active incretin levels. Extraction can be either ethanol extraction or solid phase extraction. Plasma samples are not necessarily extracted in case of measuring levels of total (active plus DPP4inactivated) incretins hormones. Details, such as antibody specificity, recovery rate, and intra/interassay coefficient of variation (CV), must be given for each assay performed. It is important to ensure that all of these recommendations are strictly adhered to when such measurements are being outsourced to testing and inspection agencies or organizations. JDS/JADEC Committee for Standardized Incretin Measurement Members of the Committee: Yutaka Seino, MD; Tokio Sanke, MD; Tsutomu Hirano, MD; Yuichiro Yamada, MD; Dais Continue reading >>

Incretin Hormones And The Satiation Signal

Incretin Hormones And The Satiation Signal

Recent research has indicated that appetite-regulating hormones from the gut may have therapeutic potential. The incretin hormone, glucagon-like peptide-1 (GLP-1), appears to be involved in both peripheral and central pathways mediating satiation. Several studies have also indicated that GLP-1 levels and responses to meals may be altered in obese subjects. Clinical trial results have shown further that two GLP-1 receptor agonists (GLP-1 RAs), exenatide and liraglutide, which are approved for the treatment of hyperglycemia in patients with type 2 diabetes, also produce weight loss in overweight subjects without diabetes. Thus, GLP-1 RAs may provide a new option for pharmacological treatment of obesity. The incretin hormones are gut hormones that amplify nutrient-induced insulin secretion in response to meal intake. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are the two most important hormones and both are thought to contribute equally to the effect.1 GLP-1 is secreted from endocrine cells in the epithelium of the small intestine thatexpress the proglucagon gene, the so-called L cells. Unlike in the pancreas, the gene product, (pre)proglucagon, is processed here to release the two glucagon-like hormones, GLP-1 and GLP-2,2 whereas the glucagon sequence is buried in an N-terminal fragment of proglucagon called glicentin.3 GLP-1 binds to a single GLP-1 receptor4 and possesses several physiological effects that contribute to the regulation of glucose (Figure 1).4, 5, 6, 7 GIP is secreted from K cells in the proximal small bowel and binds to GIP receptors expressed by pancreatic islet β cells, as well as to receptors in adipose tissue and the brain.5 A large body of data indicate that GLP-1 has an important role in satiation signali Continue reading >>

Incretin Hormones As Immunomodulators Of Atherosclerosis

Incretin Hormones As Immunomodulators Of Atherosclerosis

Introduction Diabetes is global health problem with a prevalence of more than 285 million cases worldwide and an incidence that continues to increase. The vast majority of diabetic patients (~90–95%) suffer from type 2 diabetes (T2D), whereas type 1 diabetes (T1D), accounts for 5–10% and rare forms (i.e., genetic forms of diabetes, diabetes secondary to pancreatic diseases or surgery, as well as gestational diabetes) constitute the remaining subtypes (International Diabetes Federation, 2009). Cardiovascular complications represent the primary source of morbidity and mortality in diabetic subjects (Mazzone et al., 2008) and it is well known that diabetic milieu per se accelerates the course of atherosclerosis (Nogi et al., 2012). It is also well established that T2D is caused by a combination of insulin resistance in skeletal muscle, liver, and adipose tissues and impaired insulin secretion from the pancreatic islets (Stumvoll et al., 2005). Insulin resistance is the main feature of metabolic syndrome, which refers to the clustering of cardiovascular risk factors that include diabetes, obesity, dyslipidemia, and hypertension (Bajaj and Defronzo, 2003). In relation to insulin resistance, the mechanisms that can promote both atherogenesis and advanced plaque progression likely involve both systemic factors that promote these processes, particularly dyslipidemia, but also hypertension and a proinflammatory state as well as the effect of perturbed insulin signaling at the level of the intimal cells that participate in atherosclerosis (Bornfeldt and Tabas, 2011). There is extensive evidence indicating that insulin resistance increases the risk of coronary artery disease (CAD) even in the absence of hyperglycemia (DeFronzo, 2010). In vivo studies have provided data showing Continue reading >>

Incretin - An Overview | Sciencedirect Topics

Incretin - An Overview | Sciencedirect Topics

Incretins are a kind of protein hormones whose functions include the modulation of glucose metabolism by stimulating the release of insulin by the cells and, at the same time, inhibiting the release of glucagon by pancreatic cells.30,31 Bo Ahrn, ... Carolyn F. Deacon, in Vitamins & Hormones , 2010 Incretin hormones are important for metabolism, and an understanding of the factors regulating their secretion is, therefore, fundamental for full appreciation of the complex regulation of islet function and metabolism. As reviewed here, incretin hormone secretion is influenced by nutrient ingestion, and meal size and composition, in addition to gastric emptying and gastric distension, whereas the roles of the autonomic nerves and other hormones are less clear. Furthermore, there is a diurnal variation with a more rapid incretin response to meal ingestion in the morning than in the afternoon. Incretin hormone secretion is reduced in type 2 diabetes in some, but not all studies, and may also be perturbed in obesity. Finally, to add to the complexity, antidiabetic compounds may have the capacity to affect incretin hormone secretion, either directly or indirectly, which has been demonstrated for metformin and the -glucosidase inhibitors. It is, therefore, apparent that the full picture of the regulation of incretin hormone secretion is far from complete, suggesting that more studies are required. In particular, the issue whether incretin hormone secretion is reduced in type 2 diabetes needs to be examined in larger studies with control of the wash-out period and using subjects with different degrees of glucose dysregulation. Furthermore, the potential increase in incretin hormone secretion by metformin (and, possibly, other antihypeglycemic agents) requires further study. Finall Continue reading >>

Understanding The Incretin Effect

Understanding The Incretin Effect

Kansai Electric Power Hospital, Osaka 553-0003, Japan Address all correspondence and requests for reprints to: Yutaka Seino, M.D., Ph.D., Kansai Electric Power Hospital, 2-1-7 Fukushima, Fukushima-Ku, Osaka 553-0003, Japan. Search for other works by this author on: The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 4, 1 April 2011, Pages 934935, Yutaka Seino; Understanding the Incretin Effect, The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 4, 1 April 2011, Pages 934935, It is well known that the incretin effect contributes as much as half of the insulin secretory response to oral glucose load and that this effect is reduced along with worsening glucose tolerance in those with type 2 diabetes. Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two primary incretin hormones secreted from the intestine after the ingestion of glucose and other nutrients ( 1 3 ). In type 2 diabetes patients, the insulinotropic action of GIP is diminished, whereas that of GLP-1 is substantially preserved, although secretion of the latter appears to be diminished ( 4 , 5 ). Thus, methods of enhancement of circulating concentrations of GLP-1 and/or GLP-1 receptor signaling have been established as therapeutic strategies in type 2 diabetes. GLP-1 receptor agonists and dipeptidyl-peptidase-4 (DPP-4) inhibitors are now widely and successfully used for this condition. DPP-4 inhibitors augment endogenous active GIP and GLP-1 concentrations. In this therapeutic strategy, DPP-4 inhibitors are expected to enhance the incretin effect by raising plasma concentrations of active incretin hormones. The study in this issue of JCEM by Vardarli et al. ( 6 ) assesses the incretin effect after treatment with the DPP-4 inhibitor vildagliptin i Continue reading >>

Association Between Incretin-based Drugs And The Risk Of Acute Pancreatitis

Association Between Incretin-based Drugs And The Risk Of Acute Pancreatitis

Importance The association between incretin-based drugs, such as dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, and acute pancreatitis is controversial. Objective To determine whether the use of incretin-based drugs, compared with the use of 2 or more other oral antidiabetic drugs, is associated with an increased risk of acute pancreatitis. Design, Setting, and Participants A large, international, multicenter, population-based cohort study was conducted using combined health records from 7 participating sites in Canada, the United States, and the United Kingdom. An overall cohort of 1 532 513 patients with type 2 diabetes initiating the use of antidiabetic drugs between January 1, 2007, and June 30, 2013, was included, with follow-up until June 30, 2014. Exposures Current use of incretin-based drugs compared with current use of at least 2 oral antidiabetic drugs. Main Outcomes and Measures Nested case-control analyses were conducted including hospitalized patients with acute pancreatitis matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and follow-up duration. Hazard ratios (HRs) and 95% CIs for hospitalized acute pancreatitis were estimated and compared current use of incretin-based drugs with current use of 2 or more oral antidiabetic drugs. Secondary analyses were performed to assess whether the risk varied by class of drug (DPP-4 inhibitors and GLP-1 agonists) or by duration of use. Site-specific HRs were pooled using random-effects models. Results Of 1 532 513 patients included in the analysis, 781 567 (51.0%) were male; mean age was 56.6 years. During 3 464 659 person-years of follow-up, 5165 patients were hospitalized for acute pancreatitis (incidence rate, 1.49 per 1000 person-ye Continue reading >>

Control Of Glucose Homeostasis By Incretin Hormones

Control Of Glucose Homeostasis By Incretin Hormones

In humans as well as in other animal species, the ingestion of food provides the fundamental source of energy for various cellular activities. The intake of food and the ability of controlling the plasma levels of substrates for energy production involve complex mechanisms that ensure a constantly adequate supply of metabolites both in the fasting and in the fed state. A number of hormonal peptides released from the gastrointestinal (GI) tract in response to the ingestion of food have been shown to play a critical role in the postprandial control of glucose homeostasis. They are known to act through three main mechanisms of action. These include; (1) stimulation of insulin secretion of pancreatic islet (beta) cells; (2) inhibition of hepatic gluconeogenesis by suppression of glucagon secretion; and (3) inhibition of GI motility. While for some of these hormones all three mechanisms of action are utilized under physiological conditions, others preferentially use one or a combination of two mechanisms for lowering postprandial hyperglycemia. Although the term glucoincretins (or incretins, or insulinotropic hormones) etymologically only describes factors capable of inducing insulin secretion, it is more frequently used to identify a larger class of peptides that, rather than manifesting a specific mechanism of action (i.e., insulin secretion), share the ability of controlling glucose excursion in the fed state (with or without a direct insulinotropic effect). The latter more inclusive meaning, incretins, is used in this article. This review summarizes recent advances on synthesis, secretion, blood plasma patterns, and metabolism of some of the major GI regulatory peptides acting in the postprandial state. Do you want to read the rest of this article? ... tatic mechanisms Continue reading >>

Definitions

Definitions

GLP-1 analogues mimic a hormone called incretin, which stimulates the pancreas to produce insulin when blood sugar levels rise too much. The medicines mimic a hormone called incretin, which stimulates the pancreas to produce insulin when blood sugar levels rise too much. Saxagliptin is a DPP-4 inhibitor, which is designed to work by increasing the level of so-called incretin hormones in the body that help lower blood-glucose levels. The so-called incretin hormones, GIP (short for glucose-dependent insulin-releasing polypeptide) and GLP-1 (glucagon-like peptide 1), are produced in the intestine after ingestion of a meal, and are transported via the circulation to the pancreas. JANUVIA is a selective, once-daily DPP-4 inhibitor that enhances a natural body system called the incretin system to help regulate blood sugar by increasing levels of active GLP-1 and GIP hormones. Sitagliptin is a highly selective, once-daily DPP-4 inhibitor that enhances a natural body system called the incretin system to help regulate blood sugar by increasing levels of active GLP-1 and GIP hormones; it inhibits DPP-4 over 24 hours. Exenatide is a 39-amino acid peptide and is one of a new class of diabetes medications known as incretin mimics. DPP-4 inhibitors address insulin deficiency by slowing the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide). "While we don't understand the exact mechanism, it's believed to be changes in the incretin system," he said. Continue reading >>

Effects Of Meal And Incretins In The Regulation Of Splanchnic Blood Flow

Effects Of Meal And Incretins In The Regulation Of Splanchnic Blood Flow

Abstract Objective Meal ingestion is followed by a redistribution of blood flow (BF) within the splanchnic region contributing to nutrient absorption, insulin secretion and glucose disposal, but factors regulating this phenomenon in humans are poorly known. The aim of the present study was to evaluate the organ-specific changes in BF during a mixed-meal and incretin infusions. Design A non-randomized intervention study of 10 healthy adults to study splanchnic BF regulation was performed. Methods Effects of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) infusions and mixed-meal were tested in 10 healthy, glucose tolerant subjects using PET-MRI multimodal imaging technology. Intestinal and pancreatic BF and blood volume (BV) were measured with 15O-water and 15O-carbon monoxide, respectively. Results Ingestion of a mixed-meal led to an increase in pancreatic and jejunal BF, whereas duodenal BF was unchanged. Infusion of GIP and GLP-1 reduced BF in the pancreas. However, GIP infusion doubled blood flow in the jejunum with no effect of GLP-1. Conclusion Together, our data suggest that meal ingestion leads to increases in pancreatic BF accompanied by a GIP-mediated increase in jejunal but not duodenal blood flow. Continue reading >>

Incretin Hormone

Incretin Hormone

A hormone that stimulates insulin secretion in response to meals. The two most important incretin hormones are called glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Understanding how these hormones work is helping to yield new treatments for Type 1 and Type 2 diabetes. The whole concept of incretin hormones comes from a decades-old observation that orally administered glucose provokes a far greater release of insulin than the same amount of glucose delivered by injection. Scientists postulated that there must be some signal from the gastrointestinal tract (or “gut”) that increases insulin release whenever food is consumed. A considerable amount of evidence now suggests that GLP-1 and GIP are responsible for most of this increased insulin release. Furthermore, scientists have also observed that people with Type 2 diabetes have diminished insulin release in response to meals and have speculated that they may have defects in the release or action of their incretin hormones. GLP-1 is made in the small intestine and colon and is released in response to food. It stimulates insulin secretion in a glucose-dependent manner — that is, it stimulates insulin secretion only when there is glucose in the bloodstream. GLP-1 has other beneficial effects as well: It delays stomach emptying, which slows the absorption of carbohydrate and the resulting rise in blood glucose level after meals; it curbs appetite; and animal studies have shown that it may promote regeneration of the pancreatic beta cells and fight apoptosis (programmed cell death), improving the survival of existing beta cells. GIP is made by cells in the upper small intestine and is released when glucose comes in contact with these cells. Like GLP-1, GIP affects the pancreatic b Continue reading >>

Yliss Wm, Starling Eh. On The Causation Of The So-called 'peripheral Reflex Secretion' Of The Pancreas. Proceedings Of The Royal Society Of London[biol] 1902;69:352-353

Yliss Wm, Starling Eh. On The Causation Of The So-called 'peripheral Reflex Secretion' Of The Pancreas. Proceedings Of The Royal Society Of London[biol] 1902;69:352-353

The concept that oral nutrient (glucose) administration promotes a much greater degree of insulin secretion compared to a parenteral isoglycemic glucose infusion underlies the incretin effect, namely the existence of gut-derived factors that enhance glucose-stimulated insulin secretion from the islet β-cell. The hypothetical existence of certain factors produced by the intestinal mucosa in response to nutrient ingestion that are capable of stimulating the release of substances from the endocrine pancreas and thereby reducing blood glucose levels was first postulated in the early 1900's in several landmark publications (Bayliss WM, Starling EH. On the causation of the so-called 'peripheral reflex secretion' of the pancreas. Proceedings of the Royal Society of London[Biol] 1902;69:352-353 and Moore B, Edie ES, Abram JH. On the treatment of diabetes mellitus by acid extract of duodenal mucous membrane. Biochem J 1906;1:28-38) This phenomenon has been dubbed the 'incretin effect' and is estimated to account for approximately 50-70% of the total insulin secreted following oral glucose administration. Thus, incretins are hormones that are secreted from the gastrointestinal tract into the circulation in response to nutrient ingestion that enhance glucose-stimulated insulin secretion. The term 'incretin' was subsequently used to denote these glucose-lowering, intestinal-derived factors as outlined in La Barre J. Sur les possibilites d'un traitement du diabete par l'incretine. Bull Acad R Med Belg 1932;12:620-634. With the development of the radioimmunoassay, this communication between the intestine and the endocrine pancreas was confirmed when it was demonstrated that oral glucose administration is associated with a much greater increase in plasma insulin levels when compared Continue reading >>

Concerns Over Incretin-based Drugs, Pancreatic Cancer Risk Addressed In New Study

Concerns Over Incretin-based Drugs, Pancreatic Cancer Risk Addressed In New Study

Concerns Over Incretin-Based Drugs, Pancreatic Cancer Risk Addressed in New Study Concerns Over Incretin-Based Drugs, Pancreatic Cancer Risk Addressed in New Study A total of 972,384 patients were monitored in this large-scale study A new international, multicenter study has found that incretin-based drugs, used to treat type 2 diabetes, are not associated with an increased risk of pancreatic cancer. Findings from this study, published in the BMJ, might help allay some of the concerns initially brought to the forefront by the U.S. Food and Drug Administration (FDA) in response to increased reporting of pancreatic cancer in patients taking incretin-based drugs vs. other oral antidiabetic agents (2.9 times higher with exenatide, 2.7 times higher with sitagliptin). Incretin-based drugs include dipeptidyl peptidase-4 (DPP-4) inhibitors (eg, linagliptin, sitagliptin, vildagliptin, saxagliptin) and glucagon-like peptide-1 receptor agonists (eg, exenatide, liraglutide). Previous studies which noted the pancreatic cancer risk (but which didn't specifically investigate it) were limited in a number of ways including, small sample sizes, low duration time follow-ups and a low number of specific incretin-based drugs. The findings of this new study suggests that when compared to sulfonylureas, incretin-based drugs are not associated with an increased risk of pancreatic cancer. RELATED: Incretin-Based Drugs, Congestive Heart Failure: Are They Linked? In total, 972,384 patients from 6 participating sites in Canada, the U.S., and the United Kingdom, were included. In follow-ups, with the median follow-up time ranging from 1.3 to 2.8 years, 1221 out of the 972,384 were newly diagnosed as having pancreatic cancer (incidence rate 0.60 per 1000 person years). Compared with use of sulfonyl Continue reading >>

Physiology Of Incretins (gip And Glp-1) And Abnormalities In Type 2 Diabetes - Em|consulte

Physiology Of Incretins (gip And Glp-1) And Abnormalities In Type 2 Diabetes - Em|consulte

Physiology of incretins (GIP and GLP-1) and abnormalities in type 2 diabetes Physiologie des incrtines (GLP1 et GIP) et anomalies des incrtines dans le diabte de type 2 aService de Diabtologie et dEndocrinologie et INSERM CIC9504, Hpital Saint-Louis, 101, avenue Claude Vellefaux, 75010 Paris, France bINSERM U 872, Centre de Recherche des Cordeliers, 15, rue de lcole de mdecine, 75270 Paris Cedex 06, France cInstitut Cochin, Universit Paris Descartes, CNRS (UMR 8104), Paris, France, Inserm, U567, Paris, France Incretin hormones are defined as intestinal hormones released in response to nutrient ingestion, which potentiate the glucose-induced insulin response. In humans, the incretin effect is mainly caused by two peptide hormones, glucose-dependent insulin releasing polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). GIP is secreted by K cells from the upper small intestine while GLP-1 is mainly produced in the enteroendocrine L cells located in the distal intestine. Their effect is mediated through their binding with specific receptors, though part of their biological action may also involve neural modulation. GIP and GLP-1 are both rapidly degraded into inactive metabolites by the enzyme dipeptidyl-peptidase-IV (DPP-IV). In addition to its effects on insulin secretion, GLP-1 exerts other significant actions, including stimulation of insulin biosynthesis, inhibition of glucagon secretion, inhibition of gastric emptying and acid secretion, reduction of food intake, and trophic effects on the pancreas. As the insulinotropic action of GLP-1 is preserved in type 2 diabetic patients, this peptide was likely to be developed as a therapeutic agent for this disease. The full text of this article is available in PDF format. Les incrtines sont des hormones intestinales libre Continue reading >>

New Generation Of Incretin-based Medicines Allows Coordinated Action Against Diabesity

New Generation Of Incretin-based Medicines Allows Coordinated Action Against Diabesity

New generation of incretin-based medicines allows coordinated action against diabesity The new generation of incretin-based medicines will allow a coordinated action against the combination diabetes/obesity, also known as diabesity, in some cases with only a single weekly dose, and with the likelihood of additional beneficial effects on other health complications related to this condition, such as cardiovascular and neurodegenerative diseases. The experts in diabesity who met in Vigo at the third BIOCAPS workshop all highlighted the highly promising therapeutic pathways currently being opened up as regards a pharmacological approach to this combination of the two worst epidemics of the 21st century in developed countries. The increasing incidence of this disease has driven recent research efforts, and the exchange of ideas and opinions concerning the latest breakthroughs, which is a key objective of the Biomedical Research Institute (IBI) when organising its most prestigious annual scientific meeting, is considered to be essential. During the opening of the workshop, the chairwoman of the Fundacin Biomdica Galicia Sur, Beatriz Gil de Arajo, highlighted that "the BIOCAPS project has placed the IBI, which now hosts more than 500 scientists, as a centre of reference in the field of biomedical research". The coordinator of BIOCAPS, frica Gonzlez, asserted that the programme"is an excellent opportunity to open the IBI up to society, the biomedical community and also to industry" and reiterated her confidence in the continuity of this line once the project concludes. The incorporation of scientific talent, the establishment of new collaborations, the acquisition of infrastructures, the greater visibility of the institute and the boost to its innovation activities highlight c Continue reading >>

The Role Of Incretins In Glucose Homeostasis And Diabetes Treatment

The Role Of Incretins In Glucose Homeostasis And Diabetes Treatment

Go to: I. Background and Introduction Incretins are hormones that are released from the gut into the bloodstream in response to ingestion of food, and they then modulate the insulin secretory response to the products within the nutrients in the food. The insulin secretory response of incretins, called the incretin effect, accounts for at least 50% of the total insulin secreted after oral glucose. Therefore, by definition, incretin hormones are insulinotropic (i.e., they induce insulin secretion) at usual physiological concentrations seen in the plasma after ingestion. The concept of incretins is at least a century old (Table 1). In 1902, Bayliss and Starling published their landmark manuscript, “The Mechanism of Pancreatic Secretion.” The authors found that acid infused into the digestive system caused pancreatic secretion of juices through the pancreatic duct from the pancreas, even after they cut the ennervation to the intestine. Until that time, it was thought that nervous system signals controlled secretion of pancreatic juices. They carried out ground-breaking studies that led them to conclude that the nature of the signal to the pancreas was most likely a chemical stimulus: they removed extracts from the intestinal wall after it had been stimulated by acid, injected the extracts into the bloodstream, and once again they could see juices coming from the pancreatic duct of the animal that had been injected. Therefore, they proved that the extracts must have contained a substance that must normally be secreted from the intestinal wall into the bloodstream to stimulate the flow of pancreatic juice. They called the substance “secretin.” In his “Cronian Lectures,” Starling introduced the word “hormone” (derived from the Greek word meaning “impetus”) Continue reading >>

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