The first luminal loop confers insulin responsiveness to. Glucose transporter 4 glut4, slc2a4 glut4 is an insulinsensitive glucose transporter that facilitates insulinstimulated glucose uptake in adipose tissue, skeletal muscle, and cardiac tissues that. Antiglut4, glucose transporter 4, insulinresponsive glucose transporter type 4, solute carrier family 2 facilitated glucose transporter, member 4. Decreased expression of the insulinresponsive glucose. Since the cloning of glut4 in 1989, numerous studies have attempted to dissect the molecular basis of its regulation by insulin and stimuli such as muscle contraction. Slc2a4 gene genecards glut4 protein glut4 antibody. The human protein, encoded by the gene slc2a4, is 509 amino acid residues long and has a mass of. Response to insulin is regulated by its intracellular. The amino terminus of insulinresponsive aminopeptidase. The primary regulatory mechanism by which glucose uptake takes place is via insulinstimulated transport of glucose into skeletal muscle and adipose tissue, primarily mediated by glucose transporter protein type 4 glut4. The glucose transporter 4 regulating protein tug is essential for highly insulinresponsive glucose uptake in 3t3l1 adipocytes.
Glut4 represents the major cellspecific component of the insulinresponsive vesicles irvs. Analysis of amino and carboxy terminal glut4 targeting. S both stimulate glucose transport and translocation of the insulinresponsive glucose transporter 4. Antiglut4 antibody from alomone labs is a highly specific rabbit polyclonal ab directed against an epitope of the human glucose transporter 4. Insulinregulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation. Kandror department of biochemistry, boston university school of medicine, boston, ma 02118 abstract glucose transporter isoform 4 glut4, is the sole glucose transporter. Impaired counterregulatory response to hypoglycemia and impaired glucose tolerance in brain glucose transporter 4 glut4 knockout mice the specific role of the insu the specific role of the insulinresponsive glucose transporter 4 glut4 in the brain has not been well characterized in spite of its unique distribution in key glucose sensing neurons. Biogenesis and regulation of insulinresponsive vesicles containing glut4. Acetylation of tug protein promotes the accumulation of. This process is a result of the translocation of the insulinresponsive glucose transporter 4 glut4 from specialized intracellular retention compartments to the plasma membrane 16. Sab2501472 sigmaaldrich antislc2a4 cterminal antibody produced in goat affinity isolated antibody, buffered aqueous solution synonym. Insulin binds to its receptor 1 which in turn starts many protein activation cascades 2.
We sought to evaluate the time course of insulinstimulated myocardial glucose uptake mgu in mice that had undergone ablation of glucose transporter 4 glut4. Glucose transporter type 4 glut4, also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the slc2a4 gene. Glucose transport is accomplished by a shift in the distribution of the insulinresponsive glucose transporter glut4 from intracellular compartments to. One of the primary actions of insulin on adipose and skeletal muscle is to increase glucose uptake from the blood plasma. Glucose transporter 4 an overview sciencedirect topics. The autoradiography from 1 experiment in fig 2a shows the distribution of glut 4 between. Two glucose transporter isoforms are expressed in fat cells.
Insulinresponsive glucose transportersglut8 and glut4 are. Glut4 slc2a4 is the insulinresponding glucose transporter, found predominantly in muscle cells and adipocytes fat cells. In fat and skeletal muscle cells, insulinresponsive amino peptidase irap along with glucose transporter 4 glut4 and sortilin, represents a major component protein of the insulin. Background the relative importance of glut4, the most abundant insulinresponsive glucose transporter, to modulate myocardial glucose. The insulinresponsive glucose transporter 4 glut4 has a major role in glucose uptake and metabolism in insulin target tissues i. Unlike glut4, retrograde transport of irap does not require sortilin, as retromer can directly bind to the cytoplasmic tail of irap. Being a ratelimiting step in glucose metabolism, the expression and function. Glut4 in the context of insulin resistance and type 2 diabetes. Like glut4, irap translocates to the cell surface in. The insulinresponsive glucose transporter 4 glut4 plays a key role in glucose uptake and metabolism in insulin target tissues. The effect of insulin on subcellular distribution of the glut 4 glucose transporter isoform was next analyzed. The genetically engineered muscle insulin receptor knock.
Rab5 activity regulates glut4 sorting into insulin. Regulation of glut4 and insulindependent glucose flux. A pivotal metabolic function of insulin is the stimulation of glucose uptake into muscle and adipose tissues. Regulated membrane trafficking of the insulinresponsive. Reintroduction of tug in the shrna cells not only restored highly insulinresponsive glucose. Impaired counterregulatory response to hypoglycemia and. Graphical view of domain structure for interpro entry. The first luminal loop confers insulin responsiveness to glucose transporter 4 ju youn kim and konstantin v.
Insulin responsiveness of glucose transporter 4 in 3t3l1. Listed are elisa kits for the detection of glut4, an alias name of solute carrier family 2 member 4. Small glucose transporter 4 glut4containing vesicles represent the major insulinresponsive compartment in fat and skeletal muscle cells. Insulinresponsive amino peptidase follows the glut4. The first evidence for this distinct glucose transport protein was provided by david james in 1988. Pancreatic hormones stimulate translocation of the glucose transporter isoform 4 glut4 from an intracellular location to the cell surface and facilitate the rapid insulindependent storage of. This action results in the translocation of glut4 to the cell surface and accelerates glucose uptake.
Insulindependent translocation of glucose transporter 4 glut4 to the plasma membrane of fat and skeletal muscle cells plays the key role in postprandial clearance of blood glucose. Regulating glut4 sorting into the insulinresponsive compartment in muscle cells kevin patrick foley doctorate of philosophy in biochemistry department of biochemistry university of toronto 2014 abstract skeletal muscle and adipose tissue serve as the major storage sites for glucose. Here, we show that irap, similar to glut4 and sortilin, is retrieved from endosomes to the transgolgi network by retromer. Glut4 is the insulinregulated glucose transporter found primarily in adipose tissues and striated muscle skeletal and cardiac. The insulinresponsive facilitative glucose transporter, glut4, plays an extremely important physiologic role in the partitioning of glucose among peripheral tissues. Regulated membrane trafficking of the insulinresponsive glucose transporter 4 in adipocytes. Glut1 is also expressed in adipose and muscle tissue, which are the insulinresponsive sites for glucose. Regulated membrane trafficking of the insulinresponsive glucose transporter 4. Department of pharmacological sciences, state university of new york at stony brook, stony brook, new york 11794.
Insulin mobilizes glut4 glucose transporter 4 glucose transporters from a sequestered intracellular compartment into a cell surfacerecycling pathway in fat and muscle. Molecular mechanisms of glut4 regulation in adipocytes em. Deoxyandrographolide promotes glucose uptake through. Glucose transporter 4 glut 4 is found in two major insulin target tissues. Impaired counterregulatory response to hypoglycemia and impaired glucose tolerance in brain glucose transporter 4 glut4 knockout mice the specific role of the insu the specific role of the insulinresponsive glucose transporter 4 glut4 in the brain has not been well characterized in spite of its unique distribution in key glucose.
Expression, purification, and functional characterization. After a meal, glucose that is absorbed from the digestive system and circulates in the blood now stimulates the release of insulin from the pancreas figure 4. Also the exact mechanism involved is not yet fully understood, however, in insulininduced glucose. Regulated membrane trafficking of the insulinresponsive glucose transporter 4 in adipocytes robert t. Objectives we sought to evaluate the time course of insulinstimulated myocardial glucose uptake mgu in mice that had undergone ablation of glucose transporter 4 glut4. Regulating glut4 sorting into the insulinresponsive. Insulin maintains glucose homeostasis largely by enhancing glucose uptake into muscle and adipose tissues, which is a process mediated by glucose transporter 4 glut4. In fat and skeletal muscle cells, insulinresponsive amino peptidase irap along with glucose transporter 4 glut4 and sortilin, represents a major component protein of the insulinresponsive vesicles irvs. The glucose transporter 4regulating protein tug is. The primary regulatory mechanism by which glucose uptake takes place is via insulinstimulated transport of glucose into skeletal muscle and adipose tissue, primarily mediated by glucose transporter protein type4 glut4. Solute carrier family 2, facilitated glucose transporter member 4. Elasmobranch diets consist of high quantities of protein and lipids, but very low levels of carbohydrates including glucose.
This gene is a member of the solute carrier family 2 facilitated glucose transporter family and encodes a protein that functions as an insulinregulated facilitative glucose transporter. Glut4 is the insulinregulated glucose transporter found primarily in adipose. Effect of insulin on glucose uptake and metabolism. Glut4 is a key component in glucose homeostasis and the removal of glucose. Insulinresponsive glucose transportersglut8 and glut4 are expressed in. Transcriptional regulation of the insulinresponsive. The insulinresponsive aminopeptidase irap is a constituent of the vesicles that contain the insulinregulated glucose transporter glut4.
Glut4 is the insulin regulated glucose transporter found primarily in adipose tissues and striated muscle skeletal and cardiac. Insulin resistance and glut4 glucose transporter in. Boganthe glucose transporter 4 regulating protein tug is essential for highly insulinresponsive glucose. Translocation of intracellular vesicles containing the insulinresponsive glucose transporter glut4 to the cell surface is one of the most important effects of insulin in adipose and skeletal. Regulated membrane trafficking of the insulinresponsive glucose. The increase in glucose uptake can be as much as 20 or 30fold in primary adipocytes. Glucose transporter protein content and glucose transport capacity in rat skeletal muscles. It is sequestered mainly within an intracellular compartment of these cells and thus does not function as a glucose transporter until insulin signaling causes translocation of glut 4 to the cell membrane, where it facilitates glucose. Glut4 glucose transporter type 4 slc2a4 solute carrier family 2, facilitated glucose transporter member 4 glut4. The targeting of the insulinresponsive glucose transporter, glut 4, to an intracellular compartment in adipocytes and muscle is one of the key features responsible for the unique insulin sensitivity of this transporter. Through expression of epitopetagged glut 4 mutants in 3t3l1 adipocytes, two motifs have been identified as playing a central role in glut 4. Author links open overlay panel jonathan s bogan 1 konstantin v kandror 2. However, the rectal gland has been shown to be dependent on glucose as a fuel, so we hypothesized that glucose.
The gene that encodes glut4 was cloned and mapped in 1989. Reflecting this diet, most tissues use lipids and ketone bodies as their main metabolic fuel. Differential regulation of secretory compartments containing the. Biogenesis and regulation of insulinresponsive vesicles. The discovery of the insulinresponsive glucose transporter type 4 glut4 protein in. Insulin stimulates glucose uptake into skeletal muscle mainly via the translocation of glucose transporter 4 glut4 to the plasma membrane. Protein science, the flagship journal of the protein society, serves an international forum for publishing original reports on all scientific aspects of protein molecules. In the normal cycle of fasting and refeeding, insulin is the key regulator of glut4 redistribution to the cell surface leading to increased glucose flux, yet the fate of glucose.
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