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Define Incretin

The Incretin Effect – Hormonal Obesity Xxii

The Incretin Effect – Hormonal Obesity Xxii

What is the incretin effect? With the Glycemic Index (GI), we had a physiologic scale for classifying carbohydrates. Some raise blood sugars more than others. When researchers looked at carbohydrate containing foods, there is a very close correlation between the GI and the amount of insulin released (Insulin Index – II). Insulin is the hormone predominantly involved in the regulation of blood sugar. Carbohydrates raise blood sugar and insulin rises to deal with it. Fats and proteins have a negligible effect on blood glucose. For years, it was therefore assumed that this meant that it would also have a negligible effect on insulin secretion. This was not actually true. We had just ignored this rather inconvenient fact. Since fat and protein do not raise blood sugar, there should be no effect on insulin. But proteins and their constituent parts – the amino acids can also raise insulin without any effect on the blood sugar. As far back as 1966, in the Journal of Clinical Investigation the paper “Insulin secretion in response to protein ingestion” showed that oral or intravenous administration of the amino acid leucine would result in stimulation of insulin secretion. Dr. Nuttall rediscovered this fact in 1991 in his paper “Plasma glucose and insulin response to macronutrients in non diabetic and NIDDM subjects” (Diabetes Care 1991:14:824-38). So proteins and amino acids are able to stimulate insulin without any change to the blood glucose. This required an entire change in the way we think about macronutrients. Around the same time, there was increasing interest in the hormones produced in the stomach (gut hormones), and the so-called incretin effect. In 1986, Nauck and colleagues noticed something unusual. In humans, the blood sugar response to glucose given t Continue reading >>

Incretin Mimetic Drugs For Type 2 Diabetes

Incretin Mimetic Drugs For Type 2 Diabetes

Drugs in the incretin mimetic class include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). These drugs work by mimicking the incretin hormones that the body usually produces naturally to stimulate the release of insulin in response to a meal. They are used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. Continue reading >>

Incretin

Incretin

GLP-1 and DPP-4 inhibitors Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood glucose-dependent mechanism. They also slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. They also inhibit glucagon release from the alpha cells of the islets of Langerhans. The two main candidate molecules that fulfill criteria for an incretin are the intestinal peptides glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (also known as: glucose-dependent insulinotropic polypeptide or GIP). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4); both GLP-1 and GIP are members of the glucagon peptide superfamily.[1][2][3] "Many factors stimulate insulin secretion, but the main one is blood glucose. Incretins, especially GIP and GLP-1 secreted, respectively, by K and L cells in the gut are also important" (Rang and Dale's Pharmacology (2015)). GLP-1 (7-36) amide is not very useful for treatment of type 2 diabetes mellitus, since it must be administered by continuous subcutaneous infusion. Several long-lasting analogs having insulinotropic activity have been developed, and three, exenatide (Byetta) and liraglutide (Victoza), plus exenatide extended-release (Bydureon), have been approved for use in the U.S. The main disadvantage of these GLP-1 analogs is they must be administered by subcutaneous injection. Another approach is to inhibit the enzyme that inactivates GLP-1 and GIP, DPP-4. Several DPP-4 inhibitors that can be taken orally as tablets have been developed. Once weekly dosage of Continue reading >>

Incretin Based Treatments

Incretin Based Treatments

Incretin based treatments reduce post meal blood sugars. These medicines are also euglycemics, which help return the blood sugar to the normal range. When you have type 2 diabetes, the blood sugar may be too high after a meal, even if you eat very little carbohydrate (CHO). This, in part, is due to glucagon levels staying too high after meals. Medicines, called incretin based treatments, are now available to control post-meal glucagon, and help reduce the post meal blood sugars. These medicines also are blood sugar normalizing medications or euglycemics (drugs that help return the blood sugar to the normal range). The incretin based medicines are available in two families of medicines: DPP-4 Inhibitors and GLP-1 analogs. Sitagliptin, saxagliptin, and linagliptin (approved May 2011 and is not available yet) are DPP-4 inhibitors and are taken as pills. Exenatide and liraglutide are GLP-1 analogs and are taken by injection. If you have kidney problems, the dose of the incretin based medicines may need to be adjusted. Please tell your doctor if you have kidney problems before starting these medicines. DPP-4 Inhibitors DPP-4 inhibitors are oral medicines for people with type 2 diabetes that help control blood sugar levels, especially after eating. After eating, your gut naturally releases hormones—two important ones are GLP-1 and GIP. These hormones increase insulin release to help control blood sugar levels. GLP-1 also decreases glucagon release at meals, to further control blood sugar levels. However, these hormones are quickly broken down in the body by an enzyme called DPP-4. DPP-4 inhibitors like sitagliptin and saxagliptin block DPP-4 from breaking down GLP-1 as quickly so that GLP-1 can have a longer effect in the body. While DPP-4 inhibitors may be used as an initi 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 >>

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 >>

The Incretin Approach For Diabetes Treatment

The Incretin Approach For Diabetes Treatment

Glucagon-like peptide (GLP)-1 is a gut hormone that stimulates insulin secretion, gene expression, and β-cell growth. Together with the related hormone glucose-dependent insulinotropic polypeptide (GIP), it is responsible for the incretin effect, the augmentation of insulin secretion after oral as opposed to intravenous administration of glucose. Type 2 diabetic patients typically have little or no incretin-mediated augmentation of insulin secretion. This is due to decreased secretion of GLP-1 and loss of the insulinotropic effects of GIP. GLP-1, however, retains insulinotropic effects, and the hormone effectively improves metabolism in patients with type 2 diabetes. Continuous subcutaneous administration greatly improved glucose profiles and lowered body weight and HbA1c levels. Further, free fatty acid levels were lowered, insulin resistance was improved, and β-cell performance was greatly improved. The natural peptide is rapidly degraded by the enzyme dipeptidyl peptidase IV (DPP IV), but resistant analogs as well as inhibitors of DPP IV are now under development, and both approaches have shown remarkable efficacy in experimental and clinical studies. THE INCRETIN EFFECT IN TYPE 2 DIABETES It is now recognized that inadequate secretion of insulin may be a very early element in the development of type 2 diabetes and that its progression is due to declining β-cell function (1–3). The β-cell defect is partly due to loss of β-cells, but the loss, which may amount to 50% in advanced type 2 diabetes (4), does not seem to parallel the dysfunction. This raises the possibility that the dysfunction could at least be partly due to dysregulation. Thus, dysfunction of the autonomic innervation of the islets could be responsible, perhaps particularly with respect to the ear 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 >>

Bone: Incretin Hormones Perceiver Or Receiver?

Bone: Incretin Hormones Perceiver Or Receiver?

Copyright © 2012 Ilaria Dicembrini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Novel incretin-based drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i), have been last introduced in the pharmacological treatment of type 2 diabetes. In the last few years, the interest on the relationship of gut hormones with bone metabolism in diabetes has been increasing. The aim of present paper is to examine in vitro and in vivo evidence on the connections between incretin hormones and bone metabolism. We also discuss results of clinical trials and metaanalysis, explore the effects of incretin drugs in vitro on osteogenic cells and osteoclasts, and speculate on the possibility of different effects of GLP-1 RA and DPP-4i on the risk of bone fractures risk in humans. Although existing preliminary evidence suggests a protective effect on the bone, at least for DPP-4i, further controlled, long-term studies with measurement of bone markers, bone density, and clinical fractures rates are needed to substantiate and confirm those findings. 1. Introduction Glucose, protein, and fat and mixed meal ingestion is associated with a significant reduction in markers of bone resorption, detectable by twenty minutes after feeding [1]. Bone formation is also influenced, but it seems to be less responsive to nutrients than resorption [2]. Biochemical assessment of bone turnover demonstrates that food intake is the major cause of the reduced bone turnover during daytime, which is followed by a nocturnal increase [3]. In addition, the observation that parenter Continue reading >>

Characterizing The Incretin Effect Of Amino Acids And Defining Glp-1 Role On Skeletal Muscle (incretin)

Characterizing The Incretin Effect Of Amino Acids And Defining Glp-1 Role On Skeletal Muscle (incretin)

This study has two protocols the aims of which are: To identify age-related effects of AA on incretin secretion and whether and to what extent AA exhibit a true incretin effect (gut- mediated increases in plasma insulin) in younger individuals. (Protocol 1) To define the extra-pancreatic ''novel'', insulin independent effects of glucagon like peptide-1 (GLP-1) on postprandial muscle protein and glucose metabolism and microvascular blood flow. (Protocol 2) Protocol 1: This will explore the first aim. 8 Healthy younger volunteers will be recruited to under go 3 arms cross over studies. Interventions will include oral and intravenous amino acids, in addition to intravenous GLP-1 and glucose dependent insulinotropic polypeptide (GIP). 8 older subjects also will be recruited for comparison of the response of GI hormones to amino acids oral feed between young and older men. Therefore the total number will be recruited to perform this protocol is 16. Post intervention in all visits, measurements will be taken for: Insulin, Amino acids, GLP-1, GIP, Ghrelin and peptide YY (PYY). The measurable end points for this protocol are: Gut hormones levels in response to the 2 methods of AA delivery (I.V and oral) Differences in gut hormones levels between young and older subjects when AA's are delivered orally Protocol 2: This will explore the second aim. 16 healthy older subjects will be recruited and subdivided randomly into two groups to receive either post absorptive or postprandial insulin concentrations with or without GLP-1 at physiological ranges in a cross over fashion . During acute study parameters of muscle glucose and amino acids metabolism will be tested together with muscle microvascular recruitment and macro vascular flow in the tested leg. The measurable end points for t Continue reading >>

Glp-1 Agonist, Like Byetta And Bydureon Can Help Treat Type 2 Diabetes

Glp-1 Agonist, Like Byetta And Bydureon Can Help Treat Type 2 Diabetes

GLP-1 agonist, like Byetta and Bydureon can help treat Type 2 Diabetes GLP-1 agonists are a group of medications that mimic the actions of glucagon-like peptide or GLP-1. GLP-1 is one of several naturally occurring incretin compounds that affect the body after they are released from the gut during digestion. Because of its name, GLP-1 might seem to act like glucagon that increases glucose production by the liver and raises glucose levels. Instead, GLP-1 lowers both glucose and glucagon levels. Despite their different actions, GLP-1 and glucagon are both derived from the same parent compound called proglucagon, hence the similarity in names. GLP-1 cannot be used as a drug because it is broken down in less than 2 minutes by an enzyme called DPP-4 found throughout the body. To overcome this problem, GLP-1 agonists have been developed to act like GLP-1 but not be broken down as quickly. GLP-1 agonists and natural GLP-1 work on several different organs to lower glucose levels. They: Slow glucose absorption from the gut ( Type 1 and Type 2 ) Increase insulin secretion from the pancreas when the glucose is high (Type 2) Lower glucagon levels after meals (Type 1 and Type 2) Suppress a receptor located in the hypothalamus to reduce appetite (Type 1 and Type 2) Increase beta cell mass and first phase insulin release so more insulin reaches the liver and blood more quickly (Type 2) GLP-1 agonists lower glucose levels and improve control for those on insulin, and can often substantially delay the need to start insulin in those with Type 2 diabetes. They carry a low risk of hypoglycemia, promote weight loss, and show improvements in beta cell function, lipid levels, and blood pressure. However, like other diabetes medications, they cannot compete with insulin at lowering glucose le Continue reading >>

Incretin Mimetics

Incretin Mimetics

What are Incretin mimetics Incretin mimetics are agents that act like incretin hormones such as glucagon-like peptide-1 (GLP-1). They bind to GLP-1 receptors and stimulate glucose dependent insulin release, therefore act as antihyperglycemics. Incretin mimetics also suppress appetite and inhibit glucagon secretion. They slow gastric emptying and as a result prevent steep rise in post-prandial blood glucose levels. Incretin mimetics are only used to treat type 2 diabetes. List of Incretin mimetics: Filter by: -- all conditions -- Drug Name View by: Brand | Generic Reviews Avg. Ratings Victoza (Pro, More...) generic name: liraglutide 526 reviews 8.0 Byetta (Pro, More...) generic name: exenatide 79 reviews 7.9 Saxenda (Pro, More...) generic name: liraglutide 562 reviews 7.9 Bydureon (Pro, More...) generic name: exenatide 191 reviews 6.9 Trulicity (Pro, More...) generic name: dulaglutide 337 reviews 5.9 Tanzeum (Pro, More...) generic name: albiglutide 11 reviews 4.6 Adlyxin (Pro, More...) generic name: lixisenatide 0 reviews Add rating Bydureon BCise (Pro, More...) generic name: exenatide 1 review Add rating Continue reading >>

Incretins

Incretins

The incretins are hormones that work to increase insulin secretion. The incretin concept was developed when it was observed that there is substantially more insulin secreted in response to oral glucose versus intravenous glucose, as shown in the graph at right. It was hypothesized that glucose in the digestive tract activated a feedforward mechanism that increased insulin secretion, anticipating the rise in blood glucose that would occur following absorption of ingested carbohydrates. There are two main incretin hormones in humans, GIP (glucose-dependent insulinotropic peptide; also known as gastric inhibitory peptide) and GLP-1 (glucagon-like peptide-1). Both hormones are secreted by endocrine cells that are located in the epithelium of the small intestine. Incretin hormone release is regulated in a similar way to other digestive tract hormones. An increase in the concentration of a substance in the lumen of the digestive tract (in this case glucose) acts as the trigger for hormone secretion. The mechanism of incretin action is schematized in the figure below. Glucose in the small intestine stimulates incretin release. Incretins are carried through the circulation to their target tissue: the pancreatic beta cells. Incretin stimulation of beta cells causes them to secrete more insulin in response to the same amount of blood glucose. There has been a lot of interest in developing incretin-based therapies for the treatment of type 2 diabetes mellitus (T2DM). T2DM is characterized by insulin resistance, which is a decreased responsiveness of tissues to insulin, and so it may lead to a relative insulin deficiency. Frequently, T2DM also involves defects in insulin secretion, particularly as the disease advances. There are several reasons why treatments with an incretin analo 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 >>

Incretin Hormones In Diabetes And Metabolism

Incretin Hormones In Diabetes And Metabolism

Incretin Hormones in Diabetes and Metabolism Authors: Authors: Vanita R. Aroda, MD; Robert R. Henry, MD This activity is intended for endocrinologists, other physicians, and nurses who treat diabetes patients. The goal of this activity is to outline current knowledge about the physiologic basis of the incretin hormones and the incretin effect, and to provide an overview of the antidiabetogenic potential of the incretins. Upon completion of this activity, participants will be able to: Define the terms "incretin hormone" and "incretin effect" as they relate to type 2 diabetes. Describe the biological effects of GLP-1 and GIP. Discuss the therapeutic potential of incretins in type 2 diabetes. As an organization accredited by the ACCME, Medscape requires authors and editors to disclose any significant financial relationship during the past 12 months with the manufacturer of any product that may relate to the subject matter of the educational activity, whether or not the activity is commercially supported. Authors are also asked to disclose any mention of investigational products or unapproved uses of products regulated by the U.S. Food and Drug Administration. Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Medscape designates this educational activity for a maximum of 1.0 category 1 credit(s) toward the AMA Physician's Recognition Award. Each physician should claim only those credits that reflect the time he/she actually spent in the activity. Approved for 1.0 contact hour(s) of continuing education for RNs, LPNs,LVNs and NPs. This activity is cosponsored with Medical EducationCollaborative, Inc. (MEC) and Medscape. MEC is accredited as a providerof continuing nursing Continue reading >>

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