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Which Amino Acids Stimulate Insulin Release

Insulin

Insulin

This article is about the insulin protein. For uses of insulin in treating diabetes, see insulin (medication). Not to be confused with Inulin. Insulin (from Latin insula, island) is a peptide hormone produced by beta cells of the pancreatic islets, and it is considered to be the main anabolic hormone of the body.[5] It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells.[6] In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both.[6] Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood.[7] Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat. Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited.[8] Their neighboring alpha cells, by taking their cues from the beta cells,[8] secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high.[6][8] Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin.[6][8] The secretion of insulin and glucagon into the Continue reading >>

Amino Acid Metabolism, Β-cell Function, And Diabetes

Amino Acid Metabolism, Β-cell Function, And Diabetes

Specific amino acids are known to acutely and chronically regulate insulin secretion from pancreatic β-cells in vivo and in vitro. Mitochondrial metabolism is crucial for the coupling of amino acid and glucose recognition to exocytosis of insulin granules. This is illustrated by in vitro and in vivo observations discussed in the present review. Mitochondria generate ATP, which is the main coupling messenger in insulin secretion, and other coupling factors, which serve as sensors for the control of the exocytotic process. Numerous studies have sought to identify the factors that mediate the key amplifying pathway over the Ca2+ signal in nutrient-stimulated insulin secretion. Predominantly, these factors are nucleotides (ATP, GTP, cAMP, and NADPH), although metabolites have also been proposed, such as long-chain acyl-CoA derivatives and glutamate. This scenario further highlights the importance of the key enzymes or transporters, e.g., glutamate dehydrogenase, the aspartate and alanine aminotransferases, and the malate-aspartate shuttle in the control of insulin secretion. In addition, after chronic exposure, amino acids may influence gene expression in the β-cell, which subsequently alters levels of insulin secretion. Therefore, amino acids may play a direct or indirect (via generation of putative messengers of mitochondrial origin) role in insulin secretion. Amino acids can, under appropriate conditions, enhance insulin secretion from primary islet cells and β-cell lines (1–5). In vivo, l-glutamine and l-alanine are quantitatively the most abundant amino acids in the blood and extracellular fluids followed closely by the branched chain amino acids (6). However, unlike glucose, individual amino acids do not provoke insulin secretion in vitro when added at physiologi Continue reading >>

3. Amino Acids Stimulate The Release Of Both Glucagon And Insulin

3. Amino Acids Stimulate The Release Of Both Glucagon And Insulin

In a person without diabetes, a rise in blood amino acid concentration (the result of protein metabolism) stimulates the secretion of both glucagon and insulin, so their blood sugar remains stable. But in people with diabetes, the release of glucagon without insulin or with impaired insulin response can cause our blood sugar to rise precipitously several hours after a meal high in protein. The insulin is secreted to stimulate protein synthesis--the uptake of amino acids into muscle cells--making them less available for gluconeogenesis. The glucagon is secreted to stimulate the uptake of amino acids into the cells of the liver for gluconeogenesis. So why are these two hormones battling for opposing uses of the same amino acids? Isn't that non-productive? Actually, the phenomenon serves an important purpose. As you probably know, insulin lowers the blood sugar, while glucagon raises it. In the non-diabetic state, the release of these two opposing hormones ensures that the amino acids are used for protein synthesis (because of the extra insulin) but the blood sugar doesn't drop to dangerously low levels, even if the meal was low in carbohydrate. As a result, blood glucose concentration remains reasonably stable during protein metabolism. The insulin and glucagon essentially cancel each other out in terms of their effect on blood glucose, while the insulin is still able to promote protein synthesis. But in people with diabetes, as I mentioned earlier, the release of glucagon without insulin or with impaired insulin response can cause our blood sugar to rise precipitously several hours after a meal high in protein. This is due not only to the glucagon's directly raising the blood sugar, but also to the fact that in the absence of insulin it increases the amount of the amino Continue reading >>

Mechanisms Of Amino Acid-stimulated Insulin Secretion In Congenital Hyperinsulinism

Mechanisms Of Amino Acid-stimulated Insulin Secretion In Congenital Hyperinsulinism

Mechanisms of amino acid-stimulated insulin secretion in congenital hyperinsulinism Division of Endocrinology, Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA *Correspondence address. Tel: +1-215-590-5380; Fax: +1-215-590-1605; E-mail: [email protected] Author information Article notes Copyright and License information Disclaimer Received 2012 Oct 14; Accepted 2012 Nov 14. Copyright The Author 2012. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. This article has been cited by other articles in PMC. The role of amino acids in the regulation of insulin secretion in pancreatic beta-cells is highlighted in three forms of congenital hyperinsulinism (HI), namely gain-of-function mutations of glutamate dehydrogenase (GDH), loss-of-function mutations of ATP-dependent potassium channels, and a deficiency of short-chain 3-hydroxyacyl-CoA dehydrogenase. Studies on disease mouse models of HI suggest that amino acid oxidation and signaling effects are the major mechanisms of amino acid-stimulated insulin secretion. Amino acid oxidation via GDH produces ATP and triggers insulin secretion. The signaling effect of amino acids amplifies insulin release after beta-cell depolarization and elevation of cytosolic calcium. Keywords: insulin secretion, amino acid, congenital hyperinsulinism, glutamate dehydrogenase The importance of amino acid-stimulated insulin secretion (AASIS) by pancreatic islets has long been recognized [ 1 ], but its mechanisms of action remain poorly understood. Studies on perfused rat islets in the 19 Continue reading >>

Effect Of Amino Acids And Proteins On Insulin Secretion In Man

Effect Of Amino Acids And Proteins On Insulin Secretion In Man

Summary Following the demonstration that administration of leucine accentuates the hypoglycemia of some patients with “idiopathic hypoglycaemia of childhood” (1956) and of some patients with pancreatic islet cell tumours (1959) we initiated studies to explore the mechanism of leucine-induced hypoglycaemia. Sensitivity to leucine-hypoglycaemia can be induced consistently in healthy subjects after administration of sulfonylurea compounds. Increased release of pancreatic insulin is the primary mechanism by which leucine causes a fall in blood glucose in sulfonylurea-induced as well as in naturally occurring leucine hypoglycaemia. Experimentally-induced sensitivity to leucine hypoglycaemia can be used as a model for the further study of leucine hypoglycaemia. Potentiation of insulin activity has not been demonstrated to play a role in the production of leucine-induced hypoglycaemia in man. Leucine induces release of insulin and lowers blood glucose in healthy subjects without prior administration of hypoglycaemic agents, but to a quantitatively lesser extent than in sulfonylurea-induced leucine hypoglycaemia. The more pronounced sensitivity to leucine hypoglycaemia produced experimentally by administration of sulfonylureas and that observed in some patients with “idiopathic hypoglycaemia” or functioning islet cell tumours represents a great exaggeration of what appears to be a normal physiological phenomenon. To determine the effect of leucine on insulin release under physiologic circumstances, protein meals (cooked beef or chicken liver) rich in leucine were fed to healthy subjects. The increases in plasma insulin which resulted from the ingestion of the protein meals were considerably greater than those which would have been expected to have resulted from the mode Continue reading >>

Amino Acid Metabolism, Insulin Secretion And Diabetes

Amino Acid Metabolism, Insulin Secretion And Diabetes

Abstract In addition to the primary stimulus of glucose, specific amino acids may acutely and chronically regulate insulin secretion from pancreatic beta-cells in vivo and in vitro. Mitochondrial metabolism is crucial for the coupling of glucose, alanine, glutamine and glutamate recognition with exocytosis of insulin granules. This is illustrated by in vitro and in vivo observations discussed in the present review. Mitochondria generate ATP (the main coupling messenger in insulin secretion) and other factors that serve as sensors for the control of the exocytotic process. The main factors that mediate the key amplifying pathway over the Ca(2+) signal in nutrient-stimulated insulin secretion are nucleotides (ATP, GTP, cAMP and NADPH), although metabolites have also been proposed, such as long-chain acyl-CoA derivatives and glutamate. In addition, after chronic exposure, specific amino acids may influence gene expression in the beta-cell, which have an impact on insulin secretion and cellular integrity. Therefore amino acids may play a direct or indirect (via generation of putative messengers of mitochondrial origin) role in insulin secretion. Discover the world's research 14+ million members 100+ million publications 700k+ research projects Join for free Continue reading >>

A Signaling Role Of Glutamine In Insulin Secretion*

A Signaling Role Of Glutamine In Insulin Secretion*

Children with hypoglycemia due to recessive loss of function mutations of the -cell ATP-sensitive potassium (KATP) channel can develop hypoglycemia in response to protein feeding. We hypothesized that amino acids might stimulate insulin secretion by unknown mechanisms, because the KATP channel-dependent pathway of insulin secretion is defective. We therefore investigated the effects of amino acids on insulin secretion and intracellular calcium in islets from normal and sulfonylurea receptor 1 knockout (SUR1/) mice. Even though SUR1/ mice are euglycemic, their islets are considered a suitable model for studies of the human genetic defect. SUR1/ islets, but not normal islets, released insulin in response to an amino acid mixture ramp. This response to amino acids was decreased by 60% when glutamine was omitted. Insulin release by SUR1/ islets was also stimulated by a ramp of glutamine alone. Glutamine was more potent than leucine or dimethyl glutamate. Basal intracellular calcium was elevated in SUR1/ islets and was increased further by glutamine. In normal islets, methionine sulfoximine, a glutamine synthetase inhibitor, suppressed insulin release in response to a glucose ramp. This inhibition was reversed by glutamine or by 6-diazo-5-oxo-l-norleucine, a non-metabolizable glutamine analogue. High glucose doubled glutamine levels of islets. Methionine sulfoximine inhibition of glucose stimulated insulin secretion was associated with accumulation of glutamate and aspartate. We hypothesize that glutamine plays a critical role as a signaling molecule in amino acid- and glucose-stimulated insulin secretion, and that -cell depolarization and subsequent intracellular calcium elevation are required for this glutamine effect to occur. The study of inherited disorders of insulin Continue reading >>

Unit 3- Insulin And Glucagon

Unit 3- Insulin And Glucagon

Sort steps of biosynthesis of insulin in beta-cells 1. insulin gene expressed in nucleus of B-cells (insulin mRNA) 2. translation in cytosol, synthesis of N-terminal signal sequence directs complex to RER 3. signal sequence hydrophobic and directs to lumen of RER; preproinsulin is formed 4. in RER, preproinsulin is cleaved-->proinsulin and signal sequence; disulfide bridges between A and B chains are correctly aligned with help of PDI (protein disulfide isomerase) and a molecular chaperone protein 5. properly folded proinsulin -->cis-Golgi apparatus; cleaved into C-peptide and insulin 6. C-peptide and insulin stored in vesicles ready for secretion 7. upon arrival of signal, equimolar amounts of active insulin and C-peptide are released how beta cells detect blood glucose variations 1. glucose enters B-cells via GLUT-2 (insulin INDEPENDENT glucose transporter) *glucose transport exceeds rate of glucose utilization and is not limiting 2. glucose trapped in beta cells through phosphorylation to glucose-6-P catalyzed by glucokinase 3. G6P->glycolysis->TCA cycle->ETC to produce ATP *ATP/ADP ratio increases in cell with glucose concentration 4. elevated ratio inhibits ATP-sensitive potassium channel 5. accumulation of K+ in cytosol of B-cells = membrane depolarization 6. opening of a voltage-gated calcium channel = influx of calcium 7. increase in cytosolic calcium triggers regulated exocytosis of insulin in secretory vessels minor regulators of glucagon secretion -certain amino acids stimulate secretion *note: amino acids can stimulate both glucagon and insulin -Insulin and incretins (GLP-1) inhibit secretion Neural factors: -epinephrine- stimulates release of glucagon (regardless of glucose concentration) -neural input from CNS can stimulate secretion -cortisol and growth h Continue reading >>

Insulin And Glucagon

Insulin And Glucagon

Acrobat PDF file can be downloaded here. The islets of Langerhans The pancreatic Islets of Langerhans are the sites of production of insulin, glucagon and somatostatin. The figure below shows an immunofluorescence image in which antibodies specific for these hormones have been coupled to differing fluorescence markers. We can therefore identify those cells that produce each of these three peptide hormones. You can see that most of the tissue, around 80 %, is comprised of the insulin-secreting red-colored beta cells (ß-cells). The green cells are the α-cells (alpha cells) which produce glucagon. We see also some blue cells; these are the somatostatin secreting γ-cells (gamma cells). Note that all of these differing cells are in close proximity with one another. While they primarily produce hormones to be circulated in blood (endocrine effects), they also have marked paracrine effects. That is, the secretion products of each cell type exert actions on adjacent cells within the Islet. An Introduction to secretion of insulin and glucagon The nutrient-regulated control of the release of these hormones manages tissue metabolism and the blood levels of glucose, fatty acids, triglycerides and amino acids. They are responsible for homeostasis; the minute-to-minute regulation of the body's integrated metabolism and, thereby, stabilize our inner milieu. The mechanisms involved are extremely complex. Modern medical treatment of diabetes (rapidly becoming "public enemy number one") is based on insight into these mechanisms, some of which are not completely understood. I will attempt to give an introduction to this complicated biological picture in the following section. Somewhat deeper insight will come later. The Basics: secretion Let us begin with two extremely simplified figur Continue reading >>

Fatty Acids Stimulate Insulin Secretion From Human Pancreatic Islets At Fasting Glucose Concentrations Via Mitochondria-dependent And -independent Mechanisms

Fatty Acids Stimulate Insulin Secretion From Human Pancreatic Islets At Fasting Glucose Concentrations Via Mitochondria-dependent And -independent Mechanisms

Fatty acids stimulate insulin secretion from human pancreatic islets at fasting glucose concentrations via mitochondria-dependent and -independent mechanisms Free fatty acids (FFAs) acutely stimulate insulin secretion from pancreatic islets. Conflicting results have been presented regarding this effect at non-stimulatory glucose concentration, however. The aim of our study was to investigate how long-chain FFAs affect insulin secretion from isolated human pancreatic islets in the presence of physiologically fasting glucose concentrations and to explore the contribution of mitochondria to the effects on secretion. Insulin secretion from human pancreatic islets was measured from short-term static incubation or perfusion system at fasting glucose concentration (5.5mM) with or without 4 different FFAs (palmitate, palmitoleate, stearate, and oleate). The contribution of mitochondrial metabolism to the effects of fatty acid-stimulated insulin secretion was explored. The average increase in insulin secretion, measured from statically incubated and dynamically perifused human islets, was about 2-fold for saturated free fatty acids (SFAs) (palmitate and stearate) and 3-fold for mono-unsaturated free fatty acids (MUFAs) (palmitoleate and oleate) compared with 5.5mmol/l glucose alone. Accordingly, MUFAs induced 50% and SFAs 20% higher levels of oxygen consumption compared with islets exposed to 5.5mmol/l glucose alone. The effect was due to increased glycolysis. When glucose was omitted from the medium, addition of the FFAs did not affect oxygen consumption. However, the FFAs still stimulated insulin secretion from the islets although secretion was more than halved. The mitochondria-independent action was via fatty acid metabolism and FFAR1/GPR40 signaling. The findings suggest t Continue reading >>

Glucose And Amino Acid-stimulated Insulin Release In Vivo In The European Silver Eel (anguilla Anguilla L.)

Glucose And Amino Acid-stimulated Insulin Release In Vivo In The European Silver Eel (anguilla Anguilla L.)

Volume 31, Issue 2 , February 1977, Pages 249-256 Glucose and amino acid-stimulated insulin release in vivo in the European silver eel (Anguilla anguilla L.) Author links open overlay panel Bernard W.Ince AlanThorpe Get rights and content Glucose and amino acid-stimulated insulin release was studied in vivo in cannulated European silver eels (Anguilla anguilla). Glucose-stimulated insulin release was dose dependent over a range of glucose loads (10100 mg/kg) while higher doses (300 and 500 mg/kg) produced no greater increments than 100 mg/kg. Arginine and lysine injections of 10, 25 and 100 mg/kg caused greater significant increases in plasma insulin levels than glucose at the same dose levels. Histidine (10 and 25 mg/kg) caused a small but significant reduction in the plasma insulin level. Simultaneous injection of arginine (100 mg/kg) and glucose (100 mg/kg) caused an increase in plasma insulin which was sustained for 60 min and remained significantly above the controls over the 360 min sampling period. Total insulin secretion appeared to be significantly greater over the entire sampling period than when arginine and glucose were injected alone. Continue reading >>

Secretion Of Insulin In Response To Diet And Hormones

Secretion Of Insulin In Response To Diet And Hormones

1. The Dual Nature of the Pancreas The pancreas is a complex gland active in digestion and metabolism through secretion of digestive enzymes from the exocrine portion and hormones from the endocrine portion. The exocrine pancreas, which accounts for more than 95% of the pancreas mass, is structurally comprised of lobules, with acinar cells surrounding a duct system. The endocrine pancreas makes up only 2% of the pancreatic mass and is organized into the islets of Langerhans— small semi-spherical clusters of about 1500 cells (55) dispersed throughout the pancreatic parenchyme— which produce and secrete hormones critical for glucose homeostasis. The existence of islets was first described by Paul Langerhans in the 1890s, and the functional role of islets in glucose homeostasis was first demonstrated in 1890 when Joseph von Mering and colleagues showed that dogs developed diabetes mellitus following pancreatectomy (17). Though islet mass may vary between individuals—an example is the increase in the setting of adult obesity (64)— the average adult human pancreas is estimated to contain one to two million islets (24, 73). In the human pancreas, the concentration of islets is up to two times higher in the tail compared to the head and neck. However, the cellular composition and architectural organization of cell types within the islets is preserved throughout the pancreas (82). Each pancreatic islet is composed of α, β, δ, ε and PP cells; these are primarily endocrine (hormone-secreting) cells, containing numerous secretory granules with stored hormone molecules, ready for release upon receipt of the appropriate stimulus. Insulin-producing b cells are the most common cell type, making up 50-70% of islet mass, with small islets containing a greater percentage of b Continue reading >>

Comparative Effects Of Amino Acids And Glucose On Insulin Secretion From Isolated Rat Or Mouse Islets

Comparative Effects Of Amino Acids And Glucose On Insulin Secretion From Isolated Rat Or Mouse Islets

Comparative effects of amino acids and glucose on insulin secretion from isolated rat or mouse islets Yale University School of Nursing, 100 Church Street South, New Haven, Connecticut 06536-0740, USA 1Yale University School of Medicine, Department of Internal Medicine, Fitkin 1, PO Box 208020, 333 Cedar Street, New Haven, Connecticut 06520-8020, USA (Requests for offprints should be addressed to W S Zawalich; Email: Walter.Zawalich{at}Yale.Edu) Glucose and the combination of leucine and glutamine were used to stimulate insulin secretion from rat islets during a dynamic perifusion and the responses obtained were compared with those elicited from mouse islets under identical conditions. In rat islets, glucose (15 mM) or the amino acid combination of 10 mM glutamine plus 20 mM leucine were most efficacious and peak second-phase insulin release responses were 20- to 30-fold above prestimulatory rates. In contrast to rat islet responses, sustained second-phase insulin secretory responses to the same agonists were minimally increased 1- to 2-fold from mouse islets. Parallel studies demonstrated that phospholipase C (PLC) was markedly activated in rat, but not mouse, islets by both high glucose concentrations and the amino acid combination. Additional studies documented that glucose and amino acid responses of both rat and mouse islets were amplified by carbachol or forskolin. However, wortmannin, a phosphatidylinositol 3-kinase inhibitor, amplified only the responses to glucose leaving the responses to the amino acid mixture unaltered. These observations support the concept that mitochondrial metabolism alone is minimally effective in stimulating insulin secretion from islets. The activation of the supplementary second messenger systems (PLC and/or cAMP) appears essential f Continue reading >>

Amino Acid-stimulated Insulin Secretion: The Role Of The Glutamine-glutamate-alpha-ketoglutarate Axis

Amino Acid-stimulated Insulin Secretion: The Role Of The Glutamine-glutamate-alpha-ketoglutarate Axis

Monogenic Hyperinsulinemic Hypoglycemia Disorders Amino Acid-Stimulated Insulin Secretion: The Role of the Glutamine-Glutamate-Alpha-Ketoglutarate Axis Li C.a Matschinsky F.M.b Stanley C.A.a aDivision of Endocrinology/Diabetes, The Children's Hospital of Philadelphia, and bInstitute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pa., USA Stanley CA, De Len DD (eds): Monogenic Hyperinsulinemic Hypoglycemia Disorders. Front Diabetes. Basel, Karger, 2012, vol 21, pp 112-124 I have read the Karger Terms and Conditions and agree. I have read the Karger Terms and Conditions and agree. Buy a Karger Article Bundle (KAB) and profit from a discount! If you would like to redeem your KAB credit, please log in . Save over 20% compared to the individual article price. Buy Cloud Access for unlimited viewing via different devices Immediate access to all parts of this book * The final prices may differ from the prices shown due to specifics of VAT rules. The role of amino acids in the regulation of insulin secretion has received relatively little attention because of the clinical and basic science focus on glucose and, more recently, on fatty acids as the essential determinants of this process. However, early clinical observation in 1950s and recent genetic studies of protein-sensitive hypoglycemia in children with congenital hyperinsulinism have highlighted the important role of amino acids in pancreatic beta-cell physiology and pathophysiology. Mouse models of three of these disorders have been investigated to elucidate the mechanisms of amino acid-stimulated insulin secretion (AASIS), including activating mutations of glutamate dehydrogenase (GDH), inactivating mutations of the ATP-sensitive potassium channel [sulfonylurea receptor Continue reading >>

Interaction Of Ingested Leucine With Glycine On Insulin And Glucose Concentrations

Interaction Of Ingested Leucine With Glycine On Insulin And Glucose Concentrations

Interaction of Ingested Leucine with Glycine on Insulin and Glucose Concentrations 1Endocrinology, Metabolism, and Nutrition Section, Minneapolis VA Health Care System, One Veterans Drive, Minneapolis, MN 55417, USA 2Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA 3Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55108, USA Received 18 April 2014; Accepted 14 June 2014; Published 10 July 2014 Copyright 2014 Jennifer F. Iverson et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The majority of individual amino acids increase insulin and attenuate the plasma glucose response when ingested with glucose. Objective. To determine whether ingestion of two amino acids simultaneously, with glucose, would result in an additive effect. Leucine (Leu) and glycine (Gly) were chosen because they were two of the most potent glucose-lowering amino acids when given individually. Materials and Methods. Nine subjects received test items on four separate days. The first was a water control, then 25 g glucose, or Leu + Gly (1 mmol/kg fat-free mass each) 25 g glucose, in random order. Glucose, insulin, and glucagon were measured frequently for 2.5 hours. Net areas were calculated. Results. The glucose area response decreased by 66%. The insulin area response increased by 24% after ingestion of Leu + Gly + glucose compared to ingestion of glucose alone. The decrease in glucose response was not additive; the increase in insulin response was far less than additive when compared to previously published individual amino acid results. The glucagon concentration remained Continue reading >>

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