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What Are Insulin Receptors Called

What Is The Tyrosine Kinase Signalling Pathway? How Is It Related To Cancer?

What Is The Tyrosine Kinase Signalling Pathway? How Is It Related To Cancer?

There are many ways tyrosine kinase can influence a cell to become cancerous. The tyrosine receptors play an essential role in activating MAP kinase pathway which promotes cell division. One common Mechanism of activation of MAP kinase is described below: The Insulin receptors are also a kind of Tyrosine kinase receptor. The insulin receptor has two subunits, i.e. α-subunit and β-subunit. The β-subunit is rich in Tyr residues and also has intrinsic Tyr kinase activity. When the insulin binds the IGF receptors, there would be a confirmational change in the β-subunit in such as way that the Tyr residues will be autophosphorylated. Once the Tyr residues are phosphorylated, the intrinsic kinase activity is activated which would phosphorylate the IRS-1 protein. Once the IRS-1 is phosphorylated, they would bind another protein called Grb2 proteins. The Grb2 proteins have the SH2 domain (Src Homology) which is structurally conserved protein domain in the Src oncogene. The Src domain will dock itself to the phosphorylated Tyrosine residue of the IRS-1 protein. After the attachment of the Grb2 with the IRS-1 protein, another protein called SOS protein will bind to the Grb2 protein. SOS acts as an adopter protein and binds to the SH3 domains of the Grb2 protein. The SOS protein is also known as Ras-guanine exchange protein. Thus, as the name suggests, SOS protein will help in the exchange of GDP for GTP on the Ras protein. Once the Ras protein interacts with the SOS, Ras-GDP is converted to Ras-GTP, which is an active form of Ras protein. The active Ras-GTP protein then binds the RAF-1 kinase enzyme. The RAF-1 kinase enzyme then phosphorylates and activates MAP kinase. The cascade of reaction continues. The activation of MAP kinase will eventually lead to phosphorylation and Continue reading >>

What Are Receptor Proteins?

What Are Receptor Proteins?

Cell Receptors are important proteins that regulate biological function of individual cells, enabling cells, tissues and organs to sense their environment and even influence each other by sending out chemical messengers that interact with the receptors of other cells. Simply put, receptor proteins are like sensors embedded in the outer cell membrane. Each type of receptor can only be activated by a very specific molecule, an antigen, which usually comes from outside the cell. The antigen binds to the receptor, delivering a signal to the inside of the cell. Each receptor has not only a specific antigen that binds to and activates, but also very specific functions that it tells the cell to accomplish. These functions include telling the cell to get ready to divide, increase or decrease the expression of certain genes, even turning genes off or on, metabolize glucose (sugar) into energy for the cell etc. Once the signal is received by the binding of the antigen to its receptor, the signal is passed to the inside of the cell, and then from one molecule to another (called second messengers since the first message comes from the receptor) within the cell, in a process called signal transduction. When the chemical message finally arrives at its destination, a specific action results, often performed by proteins which are chemically influenced or modified to activate or inactivate them. This is somewhat like a bucket brigade passing buckets of water from one person to another until the bucket reaches its destination and accomplishes its action of helping to put out the fire. The image above shows structurally how receptor activation and concommitant second messenger action enable changes in a cellular process. Hormones often act in this way to influence cells. A good example of Continue reading >>

What Is The Process Inside Our Body That Makes Belly Fat?

What Is The Process Inside Our Body That Makes Belly Fat?

Is adipose tissue. Adipocytes are cells that make up adipose tissue. Adipose tissue is what we call FAT. We have millions of fat cells in our body and they're not going anywhere. The fat cells that we create throughout childhood and adolescence stick with us forever (turning over once every 8 years). Fat cells hold energy in the form of triglycerides. Triglycerides are created through a process called lipogenesis that occurs in our liver and our fat cells. Neat fact! When your fat cells start taking on nutrients, they release a hormone called Leptin that tells you that you're full. Obese people can have a condition known as leptin resistance (see more on hormone resistance below), making them less likely to realize they're full. When we eat, our body breaks down food matter into its component pieces and your blood stream takes in those pieces which include fatty acids, amino acids, and sugars. When your body detects elevated limits of these components, various transport hormones are secreted like insulin and Lipoproteins. Sugar, protein, and fat do not simply enter cells. Nutrients require transport chemicals to interact with the cell membranes and shuttle the components into the cells that need them. VLDLs and LDLs are usually floating around the bloodstream. They'll suck up free fatty acids and act as a mechanism that the fatty acids can enter the cells. Insulin provides a similar mechanism for amino acids and sugars. Insulin and Lipoproteins (LDLs) are absolutely essential to life. Without insulin you wouldn't be able to generate energy and your cells couldn't get the protein they need. Without lipoproteins your cells couldn't get the fatty acids required to rebuild cell membranes. Insulin is associated with getting fat, but that's only because people eat too much. E Continue reading >>

Insr Gene

Insr Gene

The INSR gene provides instructions for making a protein called an insulin receptor, which is found in many types of cells. Insulin receptors are embedded in the outer membrane surrounding the cell, where they attach (bind) to the hormone insulin circulating in the bloodstream. Insulin plays many roles in the body, including regulating blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. The insulin receptor is initially produced as a single long protein that must be processed by being cut (cleaved) into four parts: two alpha subunits and two beta subunits. These subunits work together as a functioning receptor. The alpha subunits stick out from the surface of the cell, while the beta subunits remain inside the cell. The alpha subunits attach (bind) to insulin, which causes the beta subunits to trigger signaling pathways within the cell that influence many cell functions. Continue reading >>

Are There Insulin Receptors In The Brain?

Are There Insulin Receptors In The Brain?

Initially, the liver is the only organ who contains the molecul of Glucosis with the muscles ( for a personnal using of the myocytes, unlike to the liver, who is the main container of the glucosis for the whole body ). I don’t know if Neuronal cells have insulin receptors, but you know, the brain is responsable of 25% of our consumption of energy, so I think it’s high likely that the neuronal cells might have insulin receptor because they highly need this reserve of energy, it’s a question of survival. :) Ask New Question Continue reading >>

Insulin Receptor

Insulin Receptor

Also found in: Acronyms, Wikipedia. INSR A gene on chromosome 19p13.3-p13.2 that encodes insulin receptor, the binding of insulin to which stimulates glucose uptake. Molecular pathology Defects of INSR cause Rabson-Mendenhall syndrome, leprechaunism and hyperinsulinaemic hypoglycaemia type 5. insulin receptor A heterodimeric membrane receptor composed of α and β chains, which has tyrosine kinase activity after binding insulin; IR deficiency is a rare cause of DM and may be due to a gene rearrangement, causing a deletion in the tyrosine kinase domain, a point mutation with a loss of the ATP binding site or other genetic defect Continue reading >>

Insulin Receptor And Insulin Action

Insulin Receptor And Insulin Action

Ever since the discovery of insulin and its role in the regulation of glucose uptake and utilization, there has been great interest in insulin, its structure and the way in which it interacts with its receptor and effects signal transduction. The insulin receptor is a large disulphide-linked dimer with each monomer made up of a 719 (IR-A) or 731 (IR-B) residue α-chain and a 620 residue β-chain. The β-chain contains a 194 residue extracellular portion, a 23 residue transmembrane segment and a 403 residue intracellular region. There are three approaches to gaining information about the three dimensional structure of proteins, namely: homology searching for protein domains the structure and function of which are known; de novo structural predictions using a variety of computer programs; and direct experimentation. All three have been applied to the insulin receptor family and reveal that each IR monomer is composed of structural modules commonly found in other proteins. These are (from the N-terminus to C-terminus): a leucine-rich repeat domain (L1), a cysteine-rich region (CR), a second leucine-rich repeat domain (L2), and three fibronectin type III domains (FnIII-1, FnIII-2, and FnIII-3), with FnIII-2 containing a large (~120 residues) insert domain (ID). The ID contains the furin cleavage site that yields the α-chain and β-chain of the mature receptor monomer. The intra-cellular C-terminal region of the IR monomer contains the tyrosine kinase catalytic domain, flanked by two regulatory regions - the juxtamembrane region and the C-tail. When insulin binds to the extracellular portion of IR it induces structural changes in the extracellular domains that remove the inhibitory constraints on the intracellular tyrosine kinase domains, allowing them to transphosphorylate Continue reading >>

Insulin Receptors

Insulin Receptors

Insulin Receptors are areas on the outer part of a cell that allow the cell to join or bind with insulin that is in the blood. When the cell and insulin bind together, the cell can take glucose (sugar) from the blood and use it for energy. Phe 25B is the active site of insulin. Insulin makes contact with the insulin receptor in a hydrophobic pocket. This causes the C-terminus of the B chain to separate from the N-terminus of the A chain. This allows for more binding and reactions to occur. Although insulin stimulates a vast array of responses in its target tissues skeletal muscle, adipose tissue and the liver, they all appear to be initiated by an interaction between insulin and a protein receptor located on the cell membranes of these tissues. The insulin receptor protein can only be found on these tissues, which explains the specificity of the action. When insulin binds it induces a conformational change within the receptor, known as oligomerization, which leads to autophosphorylation of specific tyrosine residues in the cytoplasmic domains of the receptors. Insulin Receptor To view the insulin receptor in cartoon form Continue reading >>

Insulin Receptor

Insulin Receptor

The cellular receptor for insulin helps control the utilization of glucose by cells Cells throughout the body are fueled largely by glucose that is delivered through the bloodstream. A complex signaling system is used to control the process, ensuring that glucose is delivered when needed and stored when there is a surplus. Two hormones, insulin and glucagon, are at the center of this signaling system. When blood glucose levels drop, alpha cells in the pancreas release glucagon, which then stimulates liver cells to release glucose into the circulation. When blood glucose levels rise, on the other hand, beta cells in the pancreas release insulin, which promotes uptake of glucose for metabolism and storage. Both hormones are small proteins that are recognized by receptors on the surface of cells. Signal Transduction The receptor for insulin is a large protein that binds to insulin and passes its message into the cell. It has several functional parts. Two copies of the protein chains come together on the outside of the cell to form the receptor site that binds to insulin. This is connected through the membrane to two tyrosine kinases, shown here at the bottom. When insulin is not present, they are held in a constrained position, but when insulin binds, these constraints are released. They first phosphorylate and activate each other, and then phosphorylate other proteins in the signaling network inside the cell. Since the whole receptor is so flexible, researchers have determined its structure in several pieces: the insulin-binding portion is shown here from PDB entry 3loh , the transmembrane segment from 2mfr , and the tyrosine kinase from 1irk . When Things Go Wrong Problems with insulin signaling can impair the proper management of glucose levels in the blood, leading to Continue reading >>

Insulin Receptor

Insulin Receptor

The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of tyrosine kinase receptors.[5] Metabolically, the insulin receptor plays a key role in the regulation of glucose homeostasis, a functional process that under degenerate conditions may result in a range of clinical manifestations including diabetes and cancer.[6][7] Biochemically, the insulin receptor is encoded by a single gene INSR, from which alternate splicing during transcription results in either IR-A or IR-B isoforms.[8] Downstream post-translational events of either isoform result in the formation of a proteolytically cleaved α and β subunit, which upon combination are ultimately capable of homo or hetero-dimerisation to produce the ≈320 kDa disulfide-linked transmembrane insulin receptor.[8] Structure[edit] Initially, transcription of alternative splice variants derived from the INSR gene are translated to form one of two monomeric isomers; IR-A in which exon 11 is excluded, and IR-B in which exon 11 is included. Inclusion of exon 11 results in the addition of 12 amino acids upstream of the intrinsic furin proteolytic cleavage site. Colour-coded schematic of the insulin receptor Upon receptor dimerisation, after proteolytic cleavage into the α- and β-chains, the additional 12 amino acids remain present at the C-terminus of the α-chain (designated αCT) where they are predicted to influence receptor–ligand interaction.[9] Each isometric monomer is structurally organized into 8 distinct domains consists of; a leucine-rich repeat domain (L1, residues 1-157), a cysteine-rich region (CR, residues 158-310), an additional leucine rich repeat domain (L2, residues 311-470), three fibronectin type III domains; FnIII-1 (residues 471-59 Continue reading >>

What Is Insulin In Simple Words?

What Is Insulin In Simple Words?

Insulin is a hormone secreted by the pancreas to regulate the blood glucose level in our bodies. Like all other organs, pancreas's functionality is to secrete sufficient insulin by the beta cells to store all the sugar or glucose from the carbohydrates consumed in the food and use the glucose as energy. Whenever some form of physical activity is done, the glucose stored is released to compensate for the energy dissipated. Whenever the blood glucose level is higher than normal, the beta cells convert the stored sugar into energy. Thus the balance is always maintained in the body by the pancreas. When the pancreas dysfunctions, there is the risk of developing a medical condition, diabetes. The causes for diabetes are varied and differs from individual to individual. But on a very broad classification, there are two types of diabetes predominantly: Type 1 Diabetes - Generally developed in earlier stages of childhood; due to the pancreas inability to secrete insulin to control the glucose in blood. Type 2 Diabetes - Generally developed after 40 (but can occur at early stages too); due to the insufficient amount of insulin secreted by the pancreas. When insulin is not naturally secreted within, people take it via injections or insulin pump, or tablets to infuse insulin into the body. Continue reading >>

The Insulin Receptor And Its Cellular Targets1

The Insulin Receptor And Its Cellular Targets1

The pleiotropic actions of insulin are mediated by a single receptor tyrosine kinase. Structure/function relationships of the insulin receptor have been conclusively established, and the early steps of insulin signaling are known in some detail. A generally accepted paradigm is that insulin receptors, acting through insulin receptor substrates, stimulate the lipid kinase activity of phosphatidylinositol 3-kinase. The rapid rise in Tris-phosphorylated inositol (PIP3) that ensues triggers a cascade of PIP3-dependent serine/threonine kinases. Among the latter, Akt (a product of the akt protooncogene) and atypical protein kinase C isoforms are thought to be involved in insulin regulation of glucose transport and oxidation; glycogen, lipid, and protein synthesis; and modulation of gene expression. The presence of multiple insulin-regulated, PIP3-dependent kinases is consistent with the possibility that different pathways are required to regulate different biological actions of insulin. Additional work remains to be performed to understand the distal components of insulin signaling. Moreover, there exists substantial evidence for insulin receptor substrate- and/or phosphatidylinositol 3-kinase-independent pathways of insulin action. The ultimate goal of these investigations is to provide clues to the pathogenesis and treatment of the insulin resistant state that is characteristic of type 2 diabetes. The prevalence of obesity in children and adults is increasing worldwide. This demonstrates that the primary cause of obesity lies in environmental and behavioral changes rather than in genetic modifications. Among the environmental influences on body weight regulation, the percentage of fat energy of the everyday diet plays an important role. In many low-income countries, the per Continue reading >>

What Are The Advancements In The Treatments Of Diabetes?

What Are The Advancements In The Treatments Of Diabetes?

Up until relatively recently doctors were on the wrong track with diabetes. Some were still injecting insulin into patients with type 2 diabetes. They now know this is not the best first course of action. Three types of diabetes in layman’s terms Type 1 is where the pancreas can not secrete enough insulin Type 2 where too much insulin is produced because receptors are resistant to insulin. Reversible in the majority of cases through diet alone. Type 3 is Alzheimer’s (due to glycated proteins) Recent discoveries mean that diagnosis of type 1 and type 2 are not as clear as once thought. I’m a specialist practitioner in obesity and diabetes. Yes that’s right, type 2 diabetes can be reversed through diet. Absolutely. Firstly this is what is a normal insulin reaction looks like: Insulin is manufactured in the pancreas and secreted when your blood sugar levels rise. Blood sugar needs to be not too high and not too low. Insulin’s mechanism to remove sugar from blood is to put it into cells, like your muscles. If there is an excess after blood glucose has gone into cells it is then put in the liver and further excess becomes fat. What happens with type 2 When insulin is secreted the body’s cells have ‘‘receptors’ that accept the insulin’s key that then open the doors to the cell to let the glucose in. Sadly in type 2 the receptors become resistant to the insulin key. Therefore not enough energy gets into the cell. The body has a negative feedback system. Once the cells do not get enough energy a signal is sent back to the pancreas to manufacture even more insulin. This is a vicious cycle. Insulin keeps going up and resistance keeps getting worse. A drug, called metformin works by making cells receptive again but it has limitations and eventually other drugs Continue reading >>

What Is The Biochemistry Of Insulin Resistance?

What Is The Biochemistry Of Insulin Resistance?

Insulin resistance is a condition that impairs the ability to efficiently remove and process glucose from the bloodstream. Glucose, or blood sugar, is a vital energy source required by all cells, organs and systems of the body for normal function. The inability to utilize glucose in the blood results in excess levels in the blood, effects metabolism, and significantly increasing the chances of developing type 2 diabetes. How Does Insulin Resistance Happen Much like leptin resistance, insulin resistance occurs when a needed substance is present in the body, but unable to be utilized by the cells of the body. Specifically, the muscles and cells of the body do not respond or recognize the presence of insulin, resulting in decreased amounts of glucose being delivered to the cells. Insulin is a hormone produced in the pancreas and important for glucose regulation and energy production. The body reacts to this decrease in glucose in the cells by sending signals demanding more glucose for energy, As long as the pancreas can produce enough insulin, meeting the demand for increased amounts of glucose, the body appears to functions normally and glucose levels remain at healthy levels. Should the demand for glucose exceed the ability to produce insulin, blood glucose levels increase which increases the health risks associated with this condition. Causes of Insulin Resistance While researchers have yet to determine an exact cause of insulin resistance, they believe it is closely related to being overweight, having excess fat around the waist and physical inactivity. Genetics and heredity also appear to influence who develops insulin resistance. Insulin resistance risk increases with age; affecting 10% of people between the ages of 20 and 40, but nearly 40% of people over the age of Continue reading >>

Insulin Binding And Activation Of The Insulin Receptor

Insulin Binding And Activation Of The Insulin Receptor

The insulin receptor (IR) is a large, disulphide-linked, glycoprotein that spans the cell membrane with its insulin binding surfaces on the outside of the cell and its tyrosine kinase domains on the inside. IR is a symmetrical homodimer that contains two identical binding pockets, each created by the juxtapositioning of two distinct binding sites involving residues from both IR monomers (IR and IR´). The two binding pockets comprise site 1/site 2´ on one side of IR and site 1´ and site 2 on the opposite side. The current model for IR activation is that two distinct surfaces of insulin engage sequentially with either the site 1/site 2´ binding pocket or the site 1´/site 2 pocket. The formation of a site 1 – insulin - site 2 high-affinity, cross-link involves structural changes in both insulin and IR resulting in the activation of the intracellular tyrosine kinase and the initiation of the phosphorylation cascades that drive insulin signaling. Understanding how insulin binding induces signal transduction requires structures of: (i) insulin and IR in their basal states, (ii) insulin bound to the IR ectodomain, (iii) the activated IR kinase domain and (iv) the domain rearrangements associated with the formation of the high affinity insulin/IR complex that initiates activation of the intracellular kinase. Continue reading >>

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