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Thiazolidinediones
The thiazolidinediones , abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used in the treatment of diabetes mellitus type 2 that were introduced in the late 1990s. Mechanism of action Thiazolidinediones or TZDs act by activating PPARs (peroxisome proliferator-activated receptors), a group of nuclear receptors, specific for ''PPARγ'' (PPAR-gamma, PPARG). They are thus the PPARG agonists subset of PPAR agonists. The endogenous ligands for these receptors are free fatty acids (FFAs) and eicosanoids. When activated, the receptor binds to DNA in complex with the retinoid X receptor (RXR), another nuclear receptor, increasing transcription of a number of specific genes and decreasing transcription of others. The main effect of expression and repression of specific genes is an increase in the storage of fatty acids in ad ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thiazolidinedione Functional Group
The thiazolidinediones , abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used in the treatment of diabetes mellitus type 2 that were introduced in the late 1990s. Mechanism of action Thiazolidinediones or TZDs act by activating PPARs (peroxisome proliferator-activated receptors), a group of nuclear receptors, specific for ''PPARγ'' (PPAR-gamma, PPARG). They are thus the PPARG agonists subset of PPAR agonists. The endogenous ligands for these receptors are free fatty acids (FFAs) and eicosanoids. When activated, the receptor binds to DNA in complex with the retinoid X receptor (RXR), another nuclear receptor, increasing transcription of a number of specific genes and decreasing transcription of others. The main effect of expression and repression of specific genes is an increase in the storage of fatty acids in a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ciglitazone
Ciglitazone ( INN) is a thiazolidinedione. Developed by Takeda Pharmaceuticals in the early 1980s, it is considered the prototypical compound for the thiazolidinedione class. Ciglitazone was never used as a medication, but it sparked interest in the effects of thiazolidinediones. Several analogues were later developed, some of which—such as pioglitazone and troglitazone—made it to the market. Ciglitazone significantly decreases VEGF production by human granulosa cells in an in vitro study, and may potentially be used in ovarian hyperstimulation syndrome. Ciglitazone is a potent and selective PPARγ ligand. It binds to the PPARγ ligand-binding domain with an EC50 ] Half maximal effective concentration (EC50) is a measure of the concentration of a drug, antibody or toxicant which induces a Stimulus%E2%80%93response_model, response halfway between the baseline and maximum after a specified exposure time. Mo ... of 3.0 μM. Ciglitazone is active in vivo as an anti-hyperglyce ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Peroxisome Proliferator-activated Receptor
In the field of molecular biology, the peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms. Nomenclature and tissue distribution Three types of PPARs have been identified: alpha, gamma, and delta (beta): * α (alpha) - expressed in liver, kidney, heart, muscle, adipose tissue, and others * β/δ (beta/delta) - expressed in many tissues, especially in brain, adipose tissue, and skin * γ (gamma) - although transcribed by the same gene, this PPAR, by way of alternative splicing, is expressed in three forms: ** γ1 - expressed in virtually all tissues, including heart, muscle, colon, kidney, pancreas, and spleen ** γ2 - expressed mainly in adipose tissue; it is 30 amino acids longer than Π... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PPARγ
Peroxisome proliferator- activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a transcription factor that in humans is encoded by the ''PPARG'' gene. Tissue distribution PPARG is mainly present in adipose tissue, colon and macrophages. Two isoforms of PPARG are detected in the human and in the mouse: PPAR-γ1 (found in nearly all tissues except muscle) and PPAR-γ2 (mostly found in adipose tissue and the intestine). Gene expression This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Adipocyte
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. In cell culture, adipocyte progenitors can also form osteoblasts, myocytes and other cell types. There are two types of adipose tissue, white adipose tissue (WAT) and brown adipose tissue (BAT), which are also known as white and brown fat, respectively, and comprise two types of fat cells. Structure White fat cells White fat cells contain a single large lipid droplet surrounded by a layer of cytoplasm, and are known as unilocular. The nucleus is flattened and pushed to the periphery. A typical fat cell is 0.1 mm in diameter with some being twice that size, and others half that size. However, these numerical estimates of fat cell size depend largely on the measurement method and the location of the adipose tissue. The fat stored i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Coactivator (genetics)
A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA promoter site or a specific DNA regulatory sequence called an enhancer. Binding of the activator-coactivator complex increases the speed of transcription by recruiting general transcription machinery to the promoter, therefore increasing gene expression. The use of activators and coactivators allows for highly specific expression of certain genes depending on cell type and developmental stage. Some coactivators also have histone acetyltransferase (HAT) activity. HATs form large multiprotein complexes that weaken the association of histones to DNA by acetylating the N-terminal histone tail. This provides more space for the transcription machinery to bind to the promoter, therefore increasing gene expression. Activators are found in a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nuclear Receptor Coactivator 1
The nuclear receptor coactivator 1 (''NCOA1'') is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA1 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA1, in turn, acylates histones, which makes downstream DNA more accessible to transcription. Hence, NCOA1 assists nuclear receptors in the upregulation of DNA expression. NCOA1 is also frequently called steroid receptor coactivator-1 (SRC-1). Interactions Nuclear receptor coactivator 1 possesses a basic helix-loop-helix (bHLH) domain and has been shown to interact with: * Androgen receptor, * C-Fos, * C-jun, * CIITA, * CREB-binding protein, * Cyclin D1, * DDX17, * DDX5 and * Estrogen receptor alpha, * Glucocorticoid receptor, * NFKB1, * PCAF, * PPARGC1A, * Peroxisome proliferator-activated receptor alpha, * SNW1, * STAT3, * STAT6, * TRIP4, and * Thyroid hormone receptor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CREB Binding Protein
Cyclic adenosine monophosphate Response Element Binding protein Binding Protein (CREB-binding protein), also known as CREBBP or CBP or KAT3A, is a coactivator encoded by the ''CREBBP'' gene in humans, located on chromosome 16p13.3. CBP has intrinsic acetyltransferase functions; it is able to add acetyl groups to both transcription factors as well as histone lysines, the latter of which has been shown to alter chromatin structure making genes more accessible for transcription. This relatively unique acetyltransferase activity is also seen in another transcription enzyme, EP300 (p300). Together, they are known as the p300-CBP coactivator family and are known to associate with more than 16,000 genes in humans; however, while these proteins share many structural features, emerging evidence suggests that these two co-activators may promote transcription of genes with different biological functions. For example, CBP alone has been implicated in a wide variety of pathophysiologies inc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Insulin Resistance
Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood sugar). Insulin is released by the pancreas in response to carbohydrates consumed in the diet. In states of insulin resistance, the same amount of insulin does not have the same effect on glucose transport and blood sugar levels. There are many causes of insulin resistance and the underlying process is still not completely understood, but sulfate depletion may be the important factor. Risk factors for insulin resistance include obesity, sedentary lifestyle, family history of diabetes, various health conditions, and certain medications. Insulin resistance is considered a component of the metabolic syndrome. There are multiple ways to measure insulin resistance such as fasting insulin levels or glucose tolerance tests, but these are not often use ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Leptin
Leptin (from Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate energy balance by inhibiting hunger, which in turn diminishes fat storage in adipocytes. Leptin is coded for by the ''LEP'' gene. Leptin acts on cell receptors in the arcuate and ventromedial nuclei, as well as other parts of the hypothalamus and dopaminergic neurons of the ventral tegmental area, consequently mediating feeding. Although regulation of fat stores is deemed to be the primary function of leptin, it also plays a role in other physiological processes, as evidenced by its many sites of synthesis other than fat cells, and the many cell types beyond hypothalamic cells that have leptin receptors. Many of these additional functions are yet to be fully defined. In obesity, a decreased sensitivity to leptin occurs (similar to insulin resistance in type 2 diabetes), resulting in an ina ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vascular Endothelial Growth Factor
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis (the '' de novo'' formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate such as in hypoxic conditions. Serum concentration of VEGF is high in bronchial asthma and diabetes mellitus. VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, muscle following exercise, and new vessels (collateral circulation) to bypass blocked vessels. It can contribute to disease. Soli ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Angiogenesis
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise (especially in older texts). The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease. Angiogenesis is a normal and vital process in growth and development, as well as in wound healing and in the formation of granulation tissue. However, it is also a fundamental step in the transition of tumors from a benign state to a malignant one, leading to the use of angiogenesis inhibitors in the treatment of cancer. The essential role of angiogenes ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
