Absence of glucagon and insulin action reveals a role for the. Irs2 knockout mice are insulin resistant in both peripheral tissues and liver and develop type 2 diabetes. With this information scientists are aware of the molecules involved in this process the general inquiry of insulins affect on glucose absorption, can be focused narrowly to a question of insulins affect on the glut4 transporters. Insulin action increases glucose transport into most, but not all, insulinsensitive cells enhances cellular utilization and storage of glucose enhances utilization of amino acids promotes fat synthesis. In the absence of insulin, glucose cannot enter the cell. Glut4 transporters lying in wait in cytoplasmic vesicles.
Glucose transport and glucose transporters in muscle and. Pessin and colleagues examines this fast moving area. Glucose transporters and insulin action implications for insulin resistance and diabetes mellitus. Vesicles containing glut4 glucose transporters are mobilized to the plasma membrane by insulin stimulation, thereby effecting glucose transport into the cell. Insulin signaling is required for insulins direct and. Diabetes alters the expression and translocation of the insulin. Glut4 is the primary glucose transporter responsible for insulin stimulated. The most important action of insulin is to promote the transport of blood glucose into insulin dependent tissues such as the liver, muscle and adipose tissue by the regulation of glucose. Journal of basic and clinical physiology and pharmacology, volume 9, issue 24, pages 89110, issn online 21910286, issn print 07926855. A prominent feature of type 2 non insulin dependent diabetes mellitus is the inability of insulin to appropiately increase the transport of glucose into target tissue. Glucose transporter an overview sciencedirect topics. Insulin therapy in obese, noninsulindependent diabetes induces improvements in insulin action and secretion that are maintained for two weeks after insulin withdrawal. Transmembrane glucose transport in skeletal of patients non. Promoting glucose transporter4 vesicle trafficking.
Glucose transporter glut is a facilitative transport protein involved in glucose translocation across the cell membrane. Modeling and simulation of glucoseinsulin metabolism. Similarly, streptozotocin induced diabetes causes a diminished expression of the. Glucose transporters and insulin action implications for. The glucoseinsulin system is an example of a closedloop physiological system. Glucose transporters and insulin actionimplications for insulin. Insulin enables glucose uptake by adipose tissue and resting skeletal muscle.
The glut4 glucose transporter is a major mediator of this action, and insulin recruits glut4 from an intracellular pool to the plasma membrane. Glucose uptake measurement and response to insulin. A healthy person, normally has a blood glucose concentration at about 70. Irs1 knockout mice are growth retarded and do not appear to develop diabetes, but are insulin resistant in peripheral tissues, with defective glucose tolerance 26. But there are many tissues in the body that use insulinindependent glucose transporters like glut3 in the brain. The first evidence for this distinct glucose transport protein was provided by david james in 1988. Glut1 present in all human tissue, numbers of the carrier protein molecule glut1 are more numerous in red blood vessels, in the protective membrane of the blood vessels in the brain and in fetal tissues. Tanis, a recently described putative receptor for serum amyloid a, has been implicated in. Exploring the mechanism of insulin action, differential insulin. Role of glucose transporters in the cellular insulin resistance of type ii noninsulindependent diabetes mellitus. The molecular mechanism of insulin action and the regulation. The insulin receptor a critical link in glucose homeostasis and insulin action.
Jul 22, 1999 glucose transporters and insulin action implications for insulin resistance and diabetes mellitus. Insulin action increases glucose transport into most, but not all, insulin sensitive cells enhances cellular utilization and storage of glucose enhances utilization of amino acids promotes fat synthesis. Top food sources of saturated fat among us populations, what we eat in america, national health and nutrition examination survey 20092010 26. Pdf insulin action on glucose transporters through. The mammalian glucose transporters are quite similar in sequence and overall structure but are unique in their tissue distribution. Insulin was discovered more than 75 years ago, but only recently have we begun to understand the mechanisms by which insulin promotes the uptake of glucose into cells. Insulin signaling pathways that regulate glucose metabolism in muscle cells and adipocytes. Metabolic effects of insulin and glucagon structure, biosynthesis, secretion insulin dependentindependent tissues, glucose entry into cells receptors, signal pathways biological response enzymes regulated by insulin and glucagon metabolism at wellfed state and starvation diabetes mellitus. After a 5d recovery, 5h fasted mice n 811group underwent a 120min saline infusion or insulin clamp 4 mukgmin insulin with glucose maintained at 165 mgdl and received a 2deoxy3 hglucose bolus to provide an index of mgu r g for the soleus, gastrocnemius, and superficial vastus lateralis. Activation of the glucose transporter glut4 by insulin. Insulin stimulates glucose transport in muscle and fat cells by causing the redistribution of a facilitative glucose transporter, glut4, from an intracellular compartment to the cell surface. The insulinresponsive glucose transporter, glut4, is found in heart, skeletal muscle and adipose tissue, where it is responsible for the reduction in the postprandial rise in plasma glucose levels. Role of glucose transporters in the cellular insulin resistance of type.
Because glucose is a vital source of energy for all life, these transporters are present in all phyla. Herbal antihyperglycemic compound increases expression of. Regulation of glucose transporters by insulin and extracellular glucose in c 2c 12 myotubes taku nedachi and makoto kanzaki tuberotohoku university biomedical engineering research. Journal of basic and clinical physiology and pharmacology. Insulin stimulates glucose uptake in muscle and adipose cells primarily by recruiting glut4 from an intracellular storage pool to the plasma membrane. Glucose enters the beta cells of the pancreas through the glucose transporter glut2 and this is a major signal leading to.
Absence of glucagon and insulin action reveals a role for. The most important action of insulin is to promote the transport of blood glucose into insulindependent tissues such as the liver, muscle and adipose tissue by the regulation of glucose. The molecular mechanism of insulin action and the regulation of glucose and lipid metabolism c. Insulin acts by stimulating the translocation of speci. Patients with noninsulindependent diabetes mellitus niddm are characterized by defects in pancreatic 3 cell functionandinsulin action ontargettissues 1. Absence of glucagon and insulin action reveals a role for the glp1 receptor in endogenous glucose production diabetes 2015. Glut1 is insulin independent and is widely distributed in different tissues. Insulin, glucagon, and diabetes mellitus flashcards quizlet. The role of skeletal muscle in glucose transport, glucose. Glucose regulation austin community college district. Because bulk brain glucose uptake is not affected by insulin in either rats or humans, 2,3 the brain had long been considered insulin insensitive.
Insulin upregulates glut4 glucose transporter insertion in skeletal muscle and adipose tissue. Muscle and adipose tissue insulin resistance the journal of lipid. Transmembrane glucose transport in skeletal of patients. Once within cells, glucose is rapidly phosphorylated by glucokinase in the liver and hexokinase in. 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. As muscle is a principal storage site for glucose and adipose tissue for triglyceride into which glucose can be converted for storage, glut4 is important in postprandial uptake of excess glucose from the bloodstream. Evidence that translocation of the glucose transport activity. The reduction of glucose in the blood results from the action of insulin. Molecular actions of insulin on glucose transport annual. Would there be any disadvantage to have the entire body use insulinindependent transporters like glut3. The glut or slc2a family are a protein family that is found in most mammalian cells.
A prominent feature of type 2 noninsulindependent diabetes mellitus is the inability of insulin to appropiately increase the transport of glucose into target tissue. Insulinindependent glucose transport regulates insulin. Skeletal muscle is the largest glucose deposit in mammals and largely contributes to glucose homeostasis. Get a printable copy pdf file of the complete article 1. Increases insulin action and glucose utilization decreases. Wasserman, regulation of insulin stimulated muscle glucose uptake in the conscious mouse.
Despite comparable glucose areas above basal, glucoseinduced insulin secretion was higher p insulin was discovered more than 75 years ago, but only recently have we begun to understand the mechanisms by which insulin promotes the uptake of glucose into cells. Regulation of glucose transporters by insulin and extracellular glucose in c 2c 12 myotubes taku nedachi and makoto kanzaki tuberotohoku university biomedical engineering research organization. Exercise and insulin, muscle contraction, insulin action. Patients with non insulin dependent diabetes mellitus niddm are characterized by defects in pancreatic 3 cell functionandinsulin action ontargettissues 1. Role of glucose transporters in the cellular insulin. Insulin signaling and the regulation of glucose transport. The facilitative glucose transporter and insulin action chan y. In the absence of insulin, glucose transporters are recycled intracellularly. Role of glucose transporters in the cellular insulin resistance of. Glucose transporters and insulin actionimplications for. Glut4 is the insulinregulated glucose transporter found primarily in adipose tissues and striated muscle skeletal and cardiac. The full text of this article is available in pdf format. Molecular mechanisms of glut4 regulation in adipocytes em.
Molecular mechanism of insulin resistance in obesity and type 2. Biochemistryregulation of glucose transporter translocator. But there are many tissues in the body that use insulin independent glucose transporters like glut3 in the brain. Although both akt and rac1 act downstream of pi3k to facilitate insulindependent glucose uptake in skeletal muscle, signaling pathways. One of them, glut4 or the insulin sensitive glucose transporter, is uniquely expressed in skeletal muscle, cardiac muscle, and adipose tissue. Cytoplasmic side of the receptor phosphorylates itself. Saltiel more than 18 million people in the united states have diabetes mellitus, and about 90% of these have the type 2 form of the disease.
Diabetes mellitus dm causes multiple health complications for including blindness, end stage renal failure, heart disease, as well as of the lower extremity amputation. The facilitative glucose transporter and insulin action. When insulin concentrations are low, glut4 glucose transporters are present in cytoplasmic vesicles, where. Glucose transporters, insulin, and diabetes quizlet. Expression of insulin regulatable glucose transporters in. Glut4 is insulin dependent and is responsible for the majority of glucose transport into muscle and adipose cells in anabolic conditions. Would there be any disadvantage to have the entire body use insulin independent transporters like glut3. Glucose transporters and insulin action implications for insulin. A tight correlation was observed between insulin action on as160 and glucose transport in control subjects, whereas a weak correlation was observed in firstdegree relatives. The rate of insulin absorption is modelled according to berger and rodbard. Insulin mediates glucose uptake into adipose tissue and skeletal muscle through glut4 glucose transporters.
In this context, a possible explanation for the decreased contractionstimulated glucose transport in diabetes rats, is that sustained insulin deficiency leads to a decrease in the number of available glucose transporters in skeletal muscle wallberghenriksson, 1987. Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Glucose transporters and insulin actionimplications for insulin resistance and diabetes mellitus. Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Shall we devide this article is sections about procaryotes, plants, fungy etc mismeret 10. A physiological model of glucoseinsulin interaction in. Another approach to insulin administration is known as multiple daily insulin injection regimens, in which. More glut4 receptors allow glucose to be taken in more rapidly 7. Thus the understanding of the mechanisms underlying this process at the molecular level may give, an insight into the prevention. Glut4 transporters are insulin sensitive, and are found in muscle and adipose tissue.
Keywords exerciseand insulin, muscle contraction, insulin ac tion, type ii diabetes, glucose transporter. Insulin regulates brain function, but how does it get there. Sloop absence of glucagon and insulin action reveals a role for the glp1 receptor in endogenous glucose production diabetes 2015. Effect of insulin and contraction up on glucose transport. Though multiple studies suggest cinnamon can reduce glucose and insulin levels, much more research is needed to determine the optimal dosing and.
Jung the biophysics laboratory, va medical center, and the department of biophysical. Only mammalian transporters the article only contains information about mammalian glucose transporters, but theyre also present in e. This insulin responsive tissue is the primary site of the glucose uptake that is triggered by insulin stimulation 1 in type 2 diabetes, insulin resistance is observed in several tissues, including skeletal muscle, and leads to above normal blood glucose concentration. In addition, between 17 and 40 million people have insulin. An important pathologic feature of obesity, niddm, and to a lesser extent iddm is resistance to insulinstimulated glucose uptake. In adipocytes from individuals with type 2 diabetes, insulin resistance has been shown to be associated with a depletion of glucose transporters. The glucose transport proteins glut1 and glut4 facilitate glucose transport into insulin sensitive cells. Stp leads to rapid fusion of glut4 containg vesicles w the membrane 6. The latter of the two is of primary interest seeing as it is the transporter that is stimulated by insulin. Dec 18, 2014 insulin therapy is necessary for people with type 1 diabetes as well as for some with type 2 diabetes. In l6 muscle cells in culture, acute treatment 1 h with insulin causes recruitment of glucose transporters to the plasma membrane, and prolonged exposure to insulin or to glucosedeprived medium causes increased expression of glut1 mrna and glut1 protein. The glucoseinsulin system helps us to keep this steady state. Apparent translocation of intracellular transport systems to the plasma membrane.
Glucose transporters, insulin, and diabetes flashcards. Oral antidiabetic agents glucophage metformin dose range 500 2250 mgday routes available po onset uk, less than 1 hr sideadverse effects gi symptoms, hypoglycemia decreases vitamin b12 absorption lactic acidosis. In muscle, this transporter also takes up glucose upon muscle contraction. Glut4 in the context of insulin resistance and type 2 diabetes. Though multiple studies suggest cinnamon can reduce glucose and insulin levels, much more research is. Regulation of insulinstimulated muscle glucose uptake in the. Pdf the facilitative glucose transporter and insulin action.
In the healthy atria, insulin stimulation increased both glut4 and 8 translocation. Effects of nonglucose nutrients on insulin secretion and. This classical paradigm has been challenged by in vivo studies suggesting that much of insulins action on the liver may be indirect, and related to systemic, rather than hepatic, insulin effects. Skeletal muscle hasbeenshownto bethe principal site of insulin resistance, defined as a reduced ability to metabolize glucose after insulin stimulation 24.
Role of glucose transport is dependent on glucose phosphorylation capacity, endocrinology, volume 145, issue 11, 1 november 2004, pages 4912. Evidence that translocation of the glucose transport activity is the major mechanism of insulin action on glucose transport in fat cells received for publication, december 14, 1981 tetsuro kono, frances w. Shall we devide this article is sections about procaryotes, plants, fungy etc mismeret. Glucose transporters accomplish the movement of glucose from the extracellular space deriving from the bloodstream into cells. Class ii facilitative transporters the class ii facilitative transporters are headed by the fructose transporter glut5, and include glut7, glut9. Model predicts performance of glucoseresponsive insulin. Regulation of insulinstimulated muscle glucose uptake in. Evidence that translocation of the glucose transport. Dysfunction of this process known as insulin resistance causes hyperglycemia, a hallmark of diabetes and obesity.
485 154 1546 970 1578 902 1267 853 850 788 346 1513 1132 166 181 636 970 298 685 1129 1620 1542 973 391 834 339 1127 1223 910 1376 975 1365 1385 131