Gfuceinduced antphase insu lin secretion did not occur in patients with noninsulindependent. Diabetes is the condition in which the cells are not taking the glucose out of the bloodstream either due to the lack of insulin or the glut4 transporter does not work properly. Role of glucose transporters in the cellular insulin resistance of type. Get a printable copy pdf file of the complete article 1. The insulinindependent transporter allows continued transport down the glucose concentration gradient, even as the blood glucose concentration falls. Role of exercise training in the prevention and treatment. Glucose transporters, insulin, and diabetes quizlet. Before offering an explanation, it should be pointed out that the glut family.
Insulin signaling and glucose transport in skeletal muscle. Similarly, streptozotocin induced diabetes causes a diminished expression of the. 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. Suitability of 2deoxyglucose for in vitro measurement of glucose transport activity in skeletal muscle. Dec 11, 2018 medical definition of non insulin dependent diabetes medical author. The bulk of glucose that is filtered by the renal glomerulus is reabsorbed by the glucose transporters of the proximal convoluted tubular epithelium. Ijms free fulltext the role of glucose transporters. We determined insulin action on signal transduction and glucose transport in isolated vastus lateralis skeletal muscle from normal glucosetolerant firstdegree relatives of type 2 diabetic patients n 8, 41 3 years, bmi 25. Role of glucose transporters in the cellular insulin.
Jci role of glucose transporters in the cellular insulin. Transmembrane glucose transport in skeletal of patients non. Peripheral resistance to insulin is a prominent feature of both insulindependent and noninsulindependent diabetes. Which organs do not need insulin for glucose absorption. Type 2 diabetes mellitus dm is a chronic disease caused by a defect in the secretion of pancreatic insulin andor an insensitivity of target tissues to its action leading to hyperglycemia,4 contributing to morbidity and mortality.
This study proposes that the mechanism of glucose transport involves the glut4 glucose transporter being stimulated by insulin, causing it to relocate and be absorbed into tissues. What is the major mechanism for non insulin mediated glucose. Glut4 is insulindependent and is responsible for the majority of glucose transport into muscle and adipose cells in anabolic conditions. Glucose transport into muscle cell is mediated by two glucose transport proteins. Skeletal muscle hasbeenshownto bethe principal site of insulin resistance, defined as a reduced ability to metabolize glucose after insulin stimulation 24. Five facilitated diffusion glucose transporter genes and one pseudogene.
Bbb expression of glut5, the fructose transporter 40, and of a sodium dependent glucose cotransporter similar to sglt2 41 have also been reported. Pmc free article dohm gl, tapscott eb, pories wj, dabbs dj, flickinger eg, meelheim d, fushiki t, atkinson sm, elton cw, caro jf. Type 2 diabetes mellitus is adult onset, is characterized by insulin resistance, and may also be accompanied by beta cell dysfunction causing insulin deficiency. Facilitative glucose transporters journal of clinical investigation. As noted, muscle and adipose have the insulin sensitive glut4 transporter, whereas other tissues do not. Primary defects in glucose transport all appear to be extremely rare and not all. Pdf glucose transporters in human renal proximal tubular.
The role of glucose transport in insulin resistance and noninsulindependent diabetes mellitus niddm is discussed. Insulin regulates brain function, but how does it get there. Noninsulindependent diabetes mellitus remains a major cause of morbidity and premature mortality in our community. Glut4 is the insulin regulated glucose transporter found primarily in. Recent epidemiological studies indicate that individuals who maintain a physically active lifestyle are much less likely to develop impaired glucose tolerance and noninsulin. While there is evidence for the expression and activity of glucose transport with the insulin sensitive glut4 in a few selected nuclei, glucose transport into most neurons is glut3 dependent. Niddm in the human and streptozotocininduced diabetes in the rat on glucose transport. Exercise, glucose transport, and insulin sensitivity. The insulin independent transporter allows continued transport down the glucose concentration gradient, even as the blood glucose concentration falls. Over the past several years, considerable progress has been made in understanding the molecular basis for these clinically important effects of physical exercise. Physical exercise can be an important adjunct in the treatment of both noninsulindependent diabetes mellitus and insulindependent diabetes mellitus. Evidence that downregulation of bcell glucose transporters in non insulin dependent diabetes may be the cause of diabetic hyperglycemia. Additional approaches using drugs that enhance insulin secretion, suppress hepatic glucose production, and increase insulin sensitivity are available, and new agents are. Is noninsulin dependent glucose uptake a therapeutic alternative.
Pdf insulin action on glucose transporters through molecular. Cells were then stimulated with 5 n m insulin to recruit glut4 to the cell surface and washed to remove insulin in, and the return of transporters to intracellular compartments and to the basal state ba was assessed by measuring the decline in the rate of 2deoxyd glucose transport activity. Non insulin dependent diabetes mellitus niddm is attributed to a failure of pancreatic beta cells to maintain insulin secretion at a level sufficient to compensate for underlying insulin resistance. Glucose transporter glut1 allele xbai associated with. Medical definition of noninsulindependent diabetes medical author. Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non insulin dependent diabetes. Many studies show during type2 diabetes non insulin mediated glucose uptake. Bbb expression of glut5, the fructose transporter 40, and of a sodiumdependent glucose cotransporter similar to sglt2. L orci, m ravazzola, d baetens, l inman, m amherdt, r g peterson, c b newgard, j h johnson, and r h unger. Glucose transporters, insulin, and diabetes flashcards. Similarly to insulin, a single bout of exercise increases the rate of glucose. We suggest the hypothesis that insulin resistance is dependent on whether glucose is entering through glut1 or glut4 and on the two functional compartments of glucose 6phosphate formation within the cell.
Skeletal muscle is the primary site responsible for. Glut3 transporter non insulin dependent found mainly in brain cells. Metformin treatment of insulinresistant cardiomyocytes elevates glucose transport activity. Role of glucose transport in the postreceptor defect of noninsulindependent. Glucose regulation in noninsulindependent diabetes mellitus. Gfuceinduced antphase insu lin secretion did not occur in patients with non insulin dependent diabetes mellitus, but glucose induced secondphase. 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. Nonetheless, the extremely close agreement between the density of d glucose displaceable cytochala. Glut1 protein may be responsible, at least in part, for the constitutive, insulin.
Dysfunctional glucose uptake into muscle and fat cells contributes to the onset of type ii diabetes box 1. It was formerly referred to as noninsulindependent diabetes mellitus. What is the major mechanism for non insulin mediated. Type 2 diabetes mellitus is the most common form of diabetes mellitus and accounts for over 90% of all cases. New concepts for treatment of noninsulindependent diabetes. The major cellular mechanism that diminishes blood glucose when. Conversely, in ectothermic vertebrates, this and other aspects of insulinregulated metabolism are hypothetically less developed. To examine the role of glucose transport proteins in cellular insulin resistance, we studied subcutaneous adipocytes isolated from lean control, obese control body mass index bmi 33. Glut2 transporter non insulin dependent found in kidney. Thus, glut4 is insulindependent and mediates the insulinstimulated glucose disposal in muscle tissue. The glut or slc2a family are a protein family that is found in most mammalian cells. Moreover, it was found that the protective effect of physical activity was strongest for individuals at highest risk of developing niddm. Type ii or noninsulin dependent diabetes mellitus niddm occurs in 9095% of the diabetic population.
Evidence that downregulation of bcell glucose transporters in noninsulindependent diabetes may be the cause of diabetic hyperglycemia. Role of glucose transporters in the cellular insulin resistance of type ii noninsulindependent diabetes mellitus. Evidence that downregulation of betacell glucose transporters in noninsulindependent diabetes may be the cause of diabetic hyperglycemia. Ijms free fulltext the role of glucose transporters in. Although potentially amenable to control by lifestyle modification, this is difficult to achieve in practice. Expression of insulin regulatable glucose transporters in. Glut2 transporter non insulin dependent found in kidney, liver, and beta cells of the pancreas. Although desensitization mechanisms of neural insulin receptors are not yet clear, it will be worthwhile to test. Recent largescale clinical trials have shown that sglt2inhibitors reduce cardiovascular events in diabetic patients. Read expression of insulin regulatable glucose transporters in skeletal muscle from type 2 non insulin dependent diabetic patients, diabetologia on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
The major cellular mechanism that diminishes blood glucose when carbohydrates are ingested is insulin stimulated glucose transport into skeletal muscle. Noninsulindependent diabetes mellitus niddm is attributed to a failure of pancreatic beta cells to maintain insulin secretion at a level sufficient to compensate for. Family of glucosetransporter genes implications for glucose. Sodiumdependent glucose transporters the sglt transport glucose and galactose, with different af. Specific genetic defects have been identified for rare monogenic forms of niddm. It no longer appears as glucose to the gradient so the glucose can continue to enter the cell.
Diabetic kidney disease dkd is a major microvascular complication of diabetes and a common cause of endstage renal disease worldwide. However, the preceding mechanism to altered glucose metabolism. Type i is also known as insulin dependent diabetes mellitus iddm and accounts for 510% of all cases. Contrary to the widelyheld belief, there is no proof that noninsulindependent patients with type 2 diabetes benefit from glucose selfmonitoring. Transmembrane glucose transport in skeletal muscle of patients with non insulin dependent diabetes.
Evidence that downregulation of betacell glucose transporters in non insulin dependent diabetes may be the cause of diabetic hyperglycemia. Facilitative glucose uptake is mediated by a family of integral membrane transport proteins that display overlapping but distinct tissue distributions and subcellular. Both genetic and environmental factors contribute to the etiology of non insulin dependent diabetes. Family of glucosetransporter genes implications for. Similarly to insulin, a single bout of exercise increases the rate of glucose uptake into the contracting skeletal muscles, a process that is regulated by the translocation of glut4 glucose transporters to the plasma membrane and transverse tubules. Exercise, glucose transport, and insulin sensitivity annual. Although potentially amenable to control by lifestyle modification. Many studies show during type2 diabetes non insulin mediated glucose uptake will upregulate and represent a major part in the regulation of glucose homeostasis at normal condition also. Insulin is a hormone that enables glucose sugar to enter the bodys cells to be used for energy. Despite delayed absorption of the ingested glucose load, impaired glucose tolerance develops with age. Before offering an explanation, it should be pointed out that the glut family of transporters are passive, so glucose flows down its.
Few physiological parameters are more tightly and acutely regulated in humans than blood glucose concentration. Type i is also known as insulin dependent diabetes. Diabetes is the condition in which the cells are not taking the glucose out. While there is evidence for the expression and activity of glucose transport with the insulinsensitive glut4 in a few selected nuclei, glucose transport into most neurons is. To study the effect of trichosanthes cucumerina linn. Glucose transporter glut1 allele xbai associated with nephropathy in noninsulindependent diabetes mellitus. Current understanding of insulinregulated cellular glucose. Role of exercise training in the prevention and treatment of. A prominent feature of type 2 noninsulindependent diabetes mellitus is the inability of insulin to appropiately increase the transport of glucose into target tissue. In the zdf rat, a model of niddm that closely resembles the human syndrome, we have previously reported profound underexpression of glut2, the highkm facilitative glucose transporter expressed. Because glucose is a vital source of energy for all life, these transporters are present in all phyla. Skeletal muscle is the primary tissue responsible for insulindependent glucose uptake in vivo. Skeletal muscle is the primary site responsible for decreased insulin induced glucose utilization in diabetic subjects.
In adipocytes from individuals with type 2 diabetes, insulin resistance has been shown to be associated with a depletion of glucose transporters. Peripheral resistance to insulin is a prominent feature of both insulin dependent and non insulin dependent diabetes. Type 2 diabetes refers to the common form of noninsulindependent diabetes mellitus and is. The adipocytemuscle transporter is expressed exclusively in tissues that are insulin sensitlve with. The influence of aging on the kinetic response to glucose ingestion and the mechanisms underlying agerelated glucose intolerance are described. If glucose is transported though the glut1 pathway, it is further metabolized by hexokinase i via glucose 6phosphate g6p and fructose 6phosphate f6p also to hexosamines.
Non insulin dependent diabetes mellitus remains a major cause of morbidity and premature mortality in our community. The adipocytemuscle transporter is expressed exclusively in tissues that are insulin sensitlve with respect to glucose uptake. Mechanisms of agerelated glucose intolerance diabetes care. Yurong lai, in transporters in drug discovery and development, 20. As proximal tubular glucose uptake is insulin independent and hyperglycemia dependent, different pathways are thought to augment the development of chronic renal complications associated with the hyperglycemic environment in diabetes, such as advanced glycosylation end products, sorbitol accumulation, and gluconeogenesis, and the increased flux through the hexoamine pathway. Further mechanistic studies are needed to elucidate the basis of the sustained differences in glucose transporters. Intracellular insulinresponsive glucose transporter. The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and alzheimers diseases.
Jan 07, 2010 contrary to the widelyheld belief, there is no proof that non insulin dependent patients with type 2 diabetes benefit from glucose selfmonitoring. Background although multiple factors contribute to the initiation and. Insulinindependent glucose transport regulates insulin. Transmembrane glucose transport in skeletal of patients.
The facilitative and sodiumdependent glucose transporter family. However, it has been difficult to investigate this in diseases such as type 2 diabetes because of the inability to isolate primary renal cells from patients without a renal biopsy. The genetic component is heterogeneous and in some patients is probably complex. This impairment is multifactorial, being characterized by delays in glucose induced insulin secretion, insulininduced suppression of hepatic glucose. Patients with non insulin dependent diabetes mellitus niddm are characterized by defects in pancreatic 3 cell functionandinsulin action ontargettissues 1. Glucose transport is the ratelimiting step for glucose utilization in muscle, and that cellular process is defective in human and animal diabetes.
This protein is an excellent candidate for a highly specific genetic defect predisposing to insulin resistance. Glucose uptake in muscle occurs by a system of facilitated diffusion involving at least two distinct glucose transporters, glut1 and glut4. Read expression of insulin regulatable glucose transporters in skeletal muscle from type 2 noninsulindependent diabetic patients, diabetologia on deepdyve, the largest online rental. To examine the role of glucose transport proteins in cellular insulin resistance, we studied subcutaneous adipocytes isolated from lean control, obese control body mass index bmi. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non insulin dependent diabetes article pdf available in diabetes 5412. Note that blood glucose concentration in the fasted state is maintained by the liver, so that this tissue has an insulin dependent transporter, not to allow glucose uptake, but to allow the. Aberrant insulin signaling and glucose metabolism in skeletal muscle from type 2 diabetic patients may arise from genetic defects and an altered metabolic milieu. Non insulin dependent diabetes mellitus an overview.
There is eveidence for two types of glut4 transporters, a glut4ir insulin. Skeletal muscle both stores glucose as glycogen and oxidizes it to produce energy following the transport step. A, insulin resistance was induced in cardiomyocytes by an 18h treatment. Patients with noninsulindependent diabetes mellitus niddm are characterized by defects in pancreatic 3 cell functionandinsulin action ontargettissues 1. Both genetic and environmental factors contribute to the etiology of noninsulindependent diabetes.