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Incretin
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. Some incretins (GLP-1) also inhibit glucagon release from the alpha cells of the islets of Langerhans. In addition, they slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. 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 (GIP, also known as: glucose-dependent insulinotropic polypeptide). 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. Medical uses Medications based on incretins are used in the treatment of diabe ...
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Incretins 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. Some incretins (GLP-1) also inhibit glucagon release from the alpha cells of the islets of Langerhans. In addition, they slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. 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 (GIP, also known as: glucose-dependent insulinotropic polypeptide). 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. Medical uses Medications based on incretins are used in the treatment of diabe ...
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Glucagon-like Peptide-1 Receptor Agonist
Glucagon-like peptide-1 receptor agonists, also known as GLP-1 receptor agonists (GLP-1-RA) or incretin mimetics, are agonists of the GLP-1 receptor. This class of medications is used for the treatment of type 2 diabetes Some drugs are also approved for obesity. One of their advantages over older insulin secretagogues, such as sulfonylureas or meglitinides, is that they have a lower risk of causing hypoglycemia. GLP-1 has a short duration of action, so to overcome this limitation several modifications in either the drugs or the formulations are being developed. The 2022 ADA standards of medical care in diabetes include GLP-1-RA as a first line pharmacological therapy for type 2 diabetes, specifically in patients with atherosclerotic cardiovascular disease or obesity. Health effects A 2021 meta-analysis found a 12% reduction in all-cause mortality when GLP-1 analogs are used in the treatment of type 2 diabetes, as well as significant improvements in cardiovascular and renal outcome ...
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Glucagon-like Peptide-1
Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region. Alongside glucose-dependent insulinotropic peptide (GIP), GLP-1 is an incretin; thus, it has the ability to decrease blood sugar levels in a glucose-dependent manner by enhancing the secretion of insulin. Beside the insulinotropic effects, GLP-1 has been associated with numerous regulatory and protective e ...
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Exenatide
Exenatide, sold under the brand name Byetta and Bydureon among others, is a medication used to treat diabetes mellitus type 2. It is used together with diet, exercise, and potentially other antidiabetic medication. It is a treatment option after metformin and sulfonylureas. It is given by injection under the skin within an hour before the first and last meal of the day. A once-weekly injection version is also available. Common side effects include low blood sugar, nausea, dizziness, abdominal pain, and pain at the site of injection. Other serious side effects may include medullary thyroid cancer, angioedema, pancreatitis, and kidney injury. Use in pregnancy and breastfeeding is of unclear safety. Exenatide is a glucagon-like peptide-1 receptor agonist (GLP-1 receptor agonist) also known as incretin mimetics. It works by increasing insulin release from the pancreas and decreases excessive glucagon release. Exenatide was approved for medical use in the United States in 2005. In ...
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Dulaglutide
Dulaglutide, sold under the brand name Trulicity among others, is a medication used for the treatment of type 2 diabetes in combination with diet and exercise. It is also approved in the United States for the reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. It is a once-weekly injection. The most common side effects are nausea, diarrhea, vomiting, abdominal pain, and decreased appetite. It is a glucagon-like peptide-1 receptor agonist (GLP-1 agonist) consisting of GLP-1(7-37) covalently linked to an Fc fragment of human IgG4. GLP-1 is a hormone that is involved in the normalization of level of glucose in blood (glycemia). The Food and Drug Administration (FDA) approved dulaglutide for use in the United States in September 2014. It was approved for use in the European Union in November 2014. In 2020, it was the 96th most commonly prescribed medication in the Unit ...
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DPP-4 Inhibitors
Inhibitors of dipeptidyl peptidase 4 (DPP-4 inhibitors or gliptins) are a class of oral hypoglycemics that block the enzyme dipeptidyl peptidase-4 (DPP-4). They can be used to treat diabetes mellitus type 2. The first agent of the class – sitagliptin – was approved by the FDA in 2006. Glucagon increases blood glucose levels, and DPP-4 inhibitors reduce glucagon and blood glucose levels. The mechanism of DPP-4 inhibitors is to increase incretin levels (GLP-1 and GIP), which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels. A 2018 meta-analysis found no favorable effect of DPP-4 inhibitors on all-cause mortality, cardiovascular mortality, myocardial infarction or stroke in patients with type 2 diabetes. Examples Drugs belonging to this class are: * Sitagliptin (FDA approved 2006, marketed by Merck & Co. as Januvia) * Vildagliptin (EU approved 2007, marketed in the EU by Novartis as Galvus ...
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Dipeptidyl Peptidase-4
Dipeptidyl peptidase-4 (DPP4), also known as adenosine deaminase complexing protein 2 or CD26 (cluster of differentiation 26) is a protein that, in humans, is encoded by the ''DPP4'' gene. DPP4 is related to FAP, DPP8, and DPP9. The enzyme was discovered in 1966 by Hopsu-Havu and Glenner, and as a result of various studies on chemism, was called dipeptidyl peptidase IV P IV Function The protein encoded by the ''DPP4'' gene is an enzyme expressed on the surface of most cell types and is associated with immune regulation, signal transduction, and apoptosis. It is a type II transmembrane glycoprotein, but a soluble form, which lacks the intracellular and transmembrane part, is present in blood plasma and various body fluids. DPP-4 is a serine exopeptidase that cleaves X-proline or X-alanine dipeptides from the N-terminus of polypeptides. Peptide bonds involving the cyclic amino acid proline cannot be cleaved by the majority of proteases and an N-terminal X-proline "shields" ...
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Peptide Hormones
Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including humans. Most hormones can be classified as either amino acid–based hormones (amine, peptide, or protein) or steroid hormones. The former are water-soluble and act on the surface of target cells via second messengers; the latter, being lipid-soluble, move through the plasma membranes of target cells (both cytoplasmic and nuclear) to act within their nuclei. Like all peptides and proteins, peptide hormones and protein hormones are synthesized in cells from amino acids according to mRNA transcripts, which are synthesized from DNA templates inside the cell nucleus. Preprohormones, peptide hormone precursors, are then processed in several stages, typically in the endoplasmic reticulum, including removal of the N-terminal signal sequence an ...
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Secretin Family
Glucagon/gastric inhibitory polypeptide/secretin/vasoactive intestinal peptide hormones are a family of evolutionarily related peptide hormones that regulate activity of G-protein-coupled receptors from the secretin receptor family. A number of polypeptidic hormones, mainly expressed in the intestine or the pancreas, belong to a group of these structurally related peptides. One such hormone, glucagon, is widely distributed and produced in the alpha-cells of pancreatic islets. It affects glucose metabolism in the liver by inhibiting glycogen synthesis, stimulating glycogenolysis and enhancing gluconeogenesis. It also increases mobilisation of glucose, free fatty acids, and ketone bodies, which are metabolites produced in excess in diabetes mellitus. Glucagon is produced, like other peptide hormones, as part of a larger precursor (preproglucagon), which is cleaved to produce glucagon, glucagon-like protein I, glucagon-like protein II, and glicentin. The structure of glucagon its ...
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Pancreatic Islets
The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of the pancreas volume and receive 10–15% of its blood flow. The pancreatic islets are arranged in density routes throughout the human pancreas, and are important in the metabolism of glucose. Structure There are about 1 million islets distributed throughout the pancreas of a healthy adult human, each of which measures an average of about 0.2 mm in diameter.:928 Each islet is separated from the surrounding pancreatic tissue by a thin fibrous connective tissue capsule which is continuous with the fibrous connective tissue that is interwoven throughout the rest of the pancreas.:928 Microanatomy Hormones produced in the pancreatic islets are secreted directly into the blood flow by (at least) five types of cells. In rat islets, endocrin ...
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Gastrointestinal Hormone
The gastrointestinal hormones (or gut hormones) constitute a group of hormones secreted by enteroendocrine cells in the stomach, pancreas, and small intestine that control various functions of the digestive organs. Later studies showed that most of the gut peptides, such as secretin, cholecystokinin or substance P, were found to play a role of neurotransmitters and neuromodulators in the central and peripheral nervous systems. Enteroendocrine cells do not form glands but are spread throughout the digestive tract. They exert their autocrine and paracrine actions that integrate gastrointestinal function. Types The gastrointestinal hormonesVella A and Drucker DJ (2011)Chapter 39 Gastrointestinal Hormones and Gut Endocrine Tumors, pp 1697-1707. In Williams Textbook of Endocrinology (2011, 12th edition) can be divided into three main groups based upon their chemical structure. * '' Gastrin–cholecystokinin family'': gastrin and cholecystokinin * ''Secretin family'': secretin, glucagon, ...
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Physiologist
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical and physical functions in a living system. According to the classes of organisms, the field can be divided into medical physiology, animal physiology, plant physiology, cell physiology, and comparative physiology. Central to physiological functioning are biophysical and biochemical processes, homeostatic control mechanisms, and communication between cells. ''Physiological state'' is the condition of normal function. In contrast, ''pathological state'' refers to abnormal conditions, including human diseases. The Nobel Prize in Physiology or Medicine is awarded by the Royal Swedish Academy of Sciences for exceptional scientific achievements in physiology related to the field of medicine. Foundations Cells Although there are difference ...
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