Jul 18, 2019 · Glucotoxicity and lipotoxicity due to excess caloric intake and increased nutrient availability are the hallmarks of diabetes progress and disease complications [3,4,5,6]. Sep 23, 2022 · The biggest drawback of a current diabetes therapy is the treatment of the consequences not the cause of the disease. Metformin (Met) is the recommended first-line therapeutic drug for type 2 diabetes mellitus (T2DM) and exerts protective effects on β-cell damage. Increased free fatty acid turnover causes increased myocardial oxygen consumption and accumulation of intermediates contributing to myocardial lipotoxicity. Chronic hyperglycemia and hyperlipidemia can exert deleterious effects on -cell function, respectively referred to as glucotoxicity and lipotoxicity. Feb 4, 2019 · In summary, lipotoxicity, usually combined with glucotoxicity in diabetes , damages the insulin secretory function and survival of β cells. 1889. May 28, 2015 · We developed systems to study how chronic glucotoxicity and lipotoxicity might be linked to the impairment of glucose-stimulated insulin secretion (GSIS) machinery in pancreatic β-cells. Several pathways have been implicated in the May 1, 2008 · Glucotoxicity, lipotoxicity, and glucolipotoxicity are secondary phenomena that are proposed to play a role in all forms of type 2 diabetes. In accordance with the inhibition of insulin-mediated anti-lipol … Hyperglycemia may negatively affect beta-cell mass by inducing apoptosis without a compensatory increase in beta-cell proliferation and neogenesis. Thus, the restoration of β-cell function is a long-sought goal in diabetes research. Dec 9, 2023 · The goal is to develope innovative pharmaceutical therapeutics, offering significant improvements in the clinical management of DCM. Aims/hypothesisCarbohydrate-free diet prevents hyperglycaemia and beta cell destruction in the New Zealand Obese (NZO) mouse model. Concentration-dependent toxicity (as documented by caspase-3 increase) of saturated FFAs and monounsaturated FFAs in the human EndoC-βH1 beta-cell line (A). Dimitriadis and Eleni Boutati and Sotirios A. Dec 1, 2009 · Diabetes is a metabolic disorder of glucose characterized by glucotoxicity, lipotoxicity and insulin resistance. Apr 24, 2023 · When pancreatic β cell in case of dysfunction, the synthesis and secretion of insulin are reduced. Feb 1, 2020 · The pathogenesis of diabetic kidney disease is a complex process caused by both glucotoxicity and lipotoxicity due to lipid accumulation. Jan 7, 2022 · Lipotoxicity and glucotoxicity also contribute to impairments in vascular function, cardiac contractility, calcium signalling, oxidative stress, cardiac efficiency and lipoapoptosis. We are curious about the relationship Oct 1, 2020 · Role of glucotoxicity and lipotoxicity in the pathophysiology of Type 2 diabetes mellitus and emerging treatment strategies Diabet Med , 26 ( 2009 ) , pp. Chronic hyperglycemia and hyperlipidemia can exert deleterious effects on beta-cell function, respectively referred to as glucotoxicity and lipotoxicity. Sep 7, 2009 · Glucotoxicity not only affects the secretion of pancreatic hormones but also participates in insulin resistance of insulin-sensitive tissues, which include liver, skeletal muscle, and adipose tissue. 2024 Jul 18;10(15):e34716. We treated db/db mice for one week with empagliflozin and/or bezafibrate to alleviate glucotoxicity and/or liptotoxicity, respectively. It would thus appear that the disruption of ER calcium homeostasis is a common event in both glucotoxicity and lipotoxicity, making it a central actor in β cell dysfunction (Fig. Deterioration of β-cell function in T2D patients may be caused, in part, by long-term exposure to high concentrations of glucose and/or lipids. Aug 1, 2012 · On the other hand, both glucotoxicity and lipotoxicity refer to a disorder mainly resulting from the chronic conditions, and it remains very hard to accurately define or mimic the specific process of diabetic development in regards to the chronic conditions. TG prevents lipotoxicity- and glucotoxicity-induced oxidative stress and ER stress in INS-1 cells The dietary regimen dissociates the effects of obesity (lipotoxicity) from those of hyperglycaemia (glucotoxicity) in NZO mice. Aug 1, 2016 · The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. These alterations cause a lower hormonal secretion and action (insulin resistance). Our results showed Metabolic syndrome (MetS) is a risk factor for the development of cardiovascular disease (CVD) and atherosclerosis through a mechanism that involves vascular smooth muscle cell (VSMC) proliferation, lipotoxicity and glucotoxicity. ROS induced by hyperglycemia (glucotoxicity) or hyperlipidemia (lipotoxicity) under diabetic conditions, cause activation of the JNK and Foxo 1 pathways in pancreatic β-cells. Our results showed Feb 1, 2017 · Glucotoxicity and lipotoxicity are both complications of T2D and are directly involved in the progression of this prominent disease. Circulating FFAs provide the substrate for triacylglycerol formation in the liver, and may also be directly cytotoxic. The lipotoxicity of insulin resistance and the glucotoxicity resulting from pancreatic beta-cell failure act synergistically to effect the clinical manifestations and complications of type 2 diabetes. Over time, both contribute to the progressive deterioration of glucose homeostasis characteristic of type 2 diabetes. Shared biochemical properties of glucotoxicity and lipotoxicity in islets decrease citrate synthase activity and increase phosphofructokinase activity Diabetes . In cases of diabetic animals, lipid deposition is found in both tubular and glomerular portions of the kidneys, which are the major sites of diabetic nephropathy lesions. Pancreatic islets were prepared from wild-type and PACAP Nov 29, 2007 · Because hyperglycemia is a prerequisite for lipotoxicity to occur, the term glucolipotoxicity, rather than lipotoxicity, is more appropriate to describe deleterious effects of lipids on β-cell function. Mar 1, 2002 · Since lipotoxicity and glucotoxicity are two major components to induce b-cell dedifferentiation and apoptosis, and subsequently b-cell dysfunction (19, 20). Jul 18, 2024 · Allantoin reduces glucotoxicity and lipotoxicity in a type 2 diabetes rat model by modulating the PI3K and MAPK signaling pathways Heliyon . Over-load of pancreatic β-cells for the excessive insulin requirement by pathologic insulin resistance May 18, 2021 · The decreased beta-cell mass in T2D is, at least in part, attributed to beta-cell apoptosis that is triggered by diabetogenic situations such as amyloid deposits, lipotoxicity and glucotoxicity. Although cell metabolism is based on the same pathways in every cell type, tissue-specific cell differences must be taken into account. Therefore, protection against β-cell loss is an essential measure to prevent and treat diabetes Oct 13, 2014 · The use of insulin for both glucotoxicity and lipotoxicity is often only temporary and if used aggressively enough will work to reverse some of the damage done by the high glucose level. Previous studies have implicated pancreatic and duo- Jul 26, 2019 · Glucotoxicity or lipotoxicity leads to hyperglycemia and insulin secretion deficiency, which are important causes for the onset of type 2 diabetes mellitus (T2DM). In this review, we highlight the Aug 1, 2005 · The lipotoxicity of insulin resistance and the glucotoxicity resulting from pancreatic beta-cell failure act synergistically to effect the clinical manifestations and complications of type 2 diabetes. Where both glucotoxicity and lipotoxicity coexist, often in obesity, insulin resistance, diabetes and CVD, glucolipotoxicity often triggers synergistic adverse metabolic outcomes. In pancreatic β-cells, glucotoxicity and lipotoxicity can impact β-cell survival, as well as impair GSIS ( Kim and Yoon, 2011 , Nakata et al, 2010 ) as evidenced in this current study. Lipotoxicity is mainly associated with dysfunctional signaling and insulin resistance response in non-adipose tissue such as myocardium, pancreas, skeletal muscle, liver, and kidney. Dec 1, 2009 · Treatments that target reduction in glucotoxicity or lipotoxicity are outlined, including emerging strategies that target the role of glucagon‐like peptide 1 and sodium glucose co‐transporter 2. Some of these approaches include the effective targeting of impaired insulin signaling, cardiac stiffness, glucotoxicity, lipotoxicity, inflammation, oxidative stress, cardiac hypertrophy, and fibrosis. The mechanisms of glucotoxic … Glucotoxicity or lipotoxicity are concepts that imply exhaustion or functional interference, but not death, of β-cells and may also contribute to apparent β-cell failure. • Alpha cells are resistant to gluco and lipotoxicity unlike beta cells. Insulin resistance (IR)-associated S-nitrosylation of insulin-signaling proteins increases in obesity. Jul 1, 2023 · When pancreatic β cell in case of dysfunction, the synthesis and secretion of insulin are reduced. May 12, 2010 · Pituitary adenylate cyclase-activating polypeptide (PACAP), a potent insulinotropin, is localized in pancreatic islets. Nov 25, 2012 · Highlights Hyperglycemia exert “toxic” effects on the β-cell phenotype in type 2 diabetes. This study is to explore the effect of cordycepin (the molecular formula C 10 H 13 N 5 O 3), a natural adenosine isolated from Cordyceps militaris, on high glucose/lipid-induced glucotoxicity and lipotoxicity in INS-1 cells. However, the protective effects of Met treatment … Feb 1, 2023 · Among these factors high levels of circulating FFA and glucose that induce lipotoxicity and glucotoxicity, respectively, through a mechanism that involves ROS generation, contribute to the development of non-alcoholic fatty liver disease associated with insulin resistance (IR), type II diabetes and cardiovascular disease (Yamagishi et al. Jul 16, 2020 · Citation 20 Uncontrolled hyperglycemia and hyperlipidemia in type 2 diabetes induce glucotoxicity and lipotoxicity. Oct 23, 2012 · Aims/hypothesis Many of the effects of resveratrol are consistent with the activation of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1) and peroxisome proliferator-activated receptor (PPAR)γ co-activator 1α (PGC-1α), which play key roles in the regulation of lipid and glucose homeostasis, and in the control of oxidative stress. In this review, we discussed the molecular mechanisms involved in pancreatic beta-cell apoptosis under such diabetes-prone situations. In insulin resistance states, a higher level of insulin is needed to generate the Glucotoxicity, lipotoxicity, and glucolipotoxicity are secondary phenomena that are proposed to play a role in all forms of type 2 diabetes. 1998 Dec;47(12):1889-93. Hepatocyte apoptosis is a … Jul 16, 2018 · In addition, Wiederkehr et al. e34716. Ferroptosis, a new form of cell death, is associated with pancreatic islet injury in patients with T2DM. Jun 6, 2017 · Beta cell dysfunction in type 2 diabetes is thought to be secondary to glucotoxicity and/or lipotoxicity (Unger 1995; Poitout and Robertson 2002; Prentki et al. The present review discusses the role of glucotoxicity in beta-cell dysfunction in type 2 diabetes mellitus. Feb 1, 2002 · Glucotoxicity and lipotoxicity contribute over time to further deterioration of glucose homeostasis, hyperglycaemia and insulin deficit (Poitout & Robertson 2002, Polonsky 2012. Hyperglycemia and hyperlipidemia impair islet β-cell functions, being recognized as glucotoxicity and lipotoxicity. . The premise is that chronically elevated glucose levels are toxic to β-cells, that elevated lipid levels in the form of circulating free fatty acids (FFA) also have toxic effects, and that the combination of the two Mar 1, 2019 · In summary, lipotoxicity, usually combined with glucotoxicity in diabetes , damages the insulin secretory function and survival of β cells. Early treatment with agents that dampen both of these deleterious processes may delay or prevent th … Feb 3, 2021 · In contrast however, more recently, Dai C. However, these terms hold various potential biological processes, and it is not clear what precisely they refer to and to what extent they might be clinically relevant. (A) Effects of hypericin on the PDX1 mRNA level in INS-1 cells under Jan 30, 2023 · Glucotoxicity, lipotoxicity and glucolipotoxicity are the major detrimental factors responsible for defects in β-cells. The insulin-producing <i>β</i> cells are susceptible to elevated lipid levels and the ensuing lipotoxicity. • Lipotoxicity reduction has additive effects on glucotoxicity reduction. Previous Editor’s Note, Insulin Special Edition, October 2014 Jul 17, 2024 · Male Sprague-Dawley rats were fed a high-fat diet to induce insulin resistance, followed by streptozotocin injection to induce diabetes. Feb 1, 2004 · In this article, we will explore the views that chronic oxidative stress is a mechanism whereby glucose excess can damage β-cells and that lipotoxicity requires hyperglycemia to exert harmful effects, whereas glucose toxicity does not require concomitant hyperlipidemia to do so. 69 These include myocardial lipotoxicity and glucotoxicity, damage from glycated end products and reactive oxygen species, impaired calcium homeostasis, mitochondrial dysfunction, activation of the renin–angiotensin Jul 27, 2024 · As an important islet-enriched transcription factor, ChREBP, has been found to regulate the stress caused by both glucotoxicity and lipotoxicity in islet cells [21,22,23]. Lipotoxicity refers to the pathological accumulation of lipid intermediates which may lead to cellular dysfunction [47]. However, you can have high blood sugar without having diabetes. 1007/s00125-012-2747-2. The pathogenesis of diabetic kidney disease is a complex process caused by both glucotoxicity and lipotoxicity due to lipid accumulation. Here we address the gluco-, lipo-, and glucolipo-toxicities in β-cells by assessing the evidence both for and against each of them. Signaling pathways initiated in hepatocytes in response to lipotoxicity that are particularly relevant to the pathogenesis of nonalcoholic steatohepatitis are reviewed by Hirsova et al . A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on by glucose intolerance and insulin resistance Aug 1, 2015 · DOI: 10. A predominant ATP production from either fatty acids or glucose renders the heart at risk for so-called lipotoxicity and glucotoxicity, respectively. 2013 Jan;56(1):204-17. 2002). Here, we review t … Lipotoxicity , originally used to describe the destructive effects of excess fat accumulation on glucose metabolism, causes functional impairments in several metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. In pancreatic β-cells, glucotoxicity and lipotoxicity can impact β-cell survival, as well as impair GSIS (Kim and Yoon, 2011, Nakata et al, 2010) as evidenced in this current study. Consuming a high-energy, high-fat diet causes lipid accumulation in peripheral tissues (41, 165, 189); however, defining the contribution of dietary fatty acids versus adipose tissue-derived fatty acids to ectopic lipid accumulation has proved challenging because the majority of dietary fatty acids are initially stored in adipose Nov 24, 2008 · These together have been called myocardial glucotoxicity. 4 Lipotoxicity and glucotoxicity. In cases of diabetic animals, lipid deposition is found in both tubular and glomerular portions of the kidneys, which are the major sites of diabetic nephropathy … We also observe reticular calcium depletion associated with lipotoxicity that could contribute to it. INS-1 cells were treated with high (33 mM) glucose, 200 nM hypericin or a combination of the two for 72 h. A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on by glucose intolerance and insulin resistance Aug 20, 2018 · Glucotoxicity is caused by long-term high blood sugar, which is a very common symptom of diabetes. Key words:Apoptosis, Endoplasmic reticulum stress, Oxidative stress, Glucotoxicity Nov 27, 2015 · These findings suggest that alleviation of glucotoxicity and lipotoxicity for one week contributes to enhancement of β-cell proliferation and reduction in β-cell apoptosis, respectively, and could lead to the preservation of β-cell mass in db/db mice. This review focuses on recent work on how glucose homeostasis is profoundly altered by distressed adipose tissue. Manipulation of these mechanisms is protective in vitro and in Mar 27, 2019 · The mechanisms contributing to the development of diabetic cardiomyopathy have been extensively explored in animal models. Excess circulating fat, glucose, or both act on diverse cells and tissues to counteract insulin-mediated glucose uptake, hepatic regulation of glucose output, and insulin secretion. Feb 1, 2002 · Chronic hyperglycemia and hyperlipidemia can exert deleterious effects on β-cell function, respectively referred to as glucotoxicity and lipotoxicity. ROS, UPR and loss of differentiation play major roles in β-cell glucotoxicity. However, under in vivo conditions, due to a series of physiological and metabolic communications associated with different tissues under the influence of dietary and When pancreatic β cell in case of dysfunction, the synthesis and secretion of insulin are reduced. Unger and colleagues discovered that elevated plasma free fatty acid levels and triglyceride accumulation in pancreatic islets preceded impairment of glucose-induced insulin secretion and systemic hyperglycemia in the Zucker The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. 1185 - 1192 Crossref View in Scopus Google Scholar It is proposed that chronic hyperglycemia, independent of hyperlipidemia, is toxic for beta-cell function, whereas chronic hyper Lipotoxicity is deleterious only in the context of concomitant hyper glycemia. Lastly, changes in protein acetylation, protein methylation and DNA methylation contribute to a myriad of gene expression and protein activity changes. We developed systems to study how chronic glucotoxicity and lipotoxicity might be linked to the impairment of glucose-stimulated insulin secretion (GSIS) machinery in pancreatic β-cells. The underlying concept is that once the primary pathogenesis of diabetes is established, probably involving both genetic and environmental forces, hyperglycemia and very commonly hyperlipidemia ensue and Jun 1, 2004 · Recent evidence points toward decreased oxidative capacity and mitochondrial aberrations as a major contributor to the development of insulin resistance and type 2 diabetes. et al. However, you can have high blood Feb 29, 2016 · The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. 2024. 05. Protein-mediated signaling clearly plays important roles in these metabolic stress responses, and metabolic stress–induced changes in gene expression have been Mar 1, 2022 · Lipotoxicity is relatively well understood in the organs mentioned above, while there are very few comprehensive descriptions of the effects of lipotoxicity on cell metabolism. Several molecules found to be increased in MetS, including free fatty … The mechanisms of glucotoxicity involve several transcription factors and are, at least in part, mediated by generation of chronic oxidative stress. Over time, both contribute to the Feb 1, 2017 · Glucotoxicity and lipotoxicity are both complications of T2D and are directly involved in the progression of this prominent disease. (A) Effects of hypericin on the PDX1 mRNA level in INS-1 cells under glucotoxicity. A decrease in islet β-cell mass is closely associated with the development and progression of diabetes. heliyon. Glucose toxicity refers to the structural and functional damage in the beta cells and target tissues of insulin, caused by chronic hyperglycemia. 12. 12 13 If glucotoxicity and/or lipotoxicity develop in intestinal L-cells that secrete GLP-1, insulin secretion would also be decreased, and it becomes difficult to reduce hyperglycemia. • This may contribute to the observed GLP-1 abnormalities in type 2 diabetes. yexcr. Jun 2, 2019 · Hypericin protects INS-1 cells from glucotoxicity and lipotoxicity via Erk signaling and maintianing PDX1 expression. DOI: 10. Here, we review the current evidence supporting the role of pancreatic β-cell lipo- and glucolipotoxicity in type 2 diabetes, including lipid-based interventions in humans, prospective epidemiological studies and human genetic findings. β-Cell “glucotoxicity” involves complex cellular and molecular mechanisms. Remarkably, in most circumstances, early failure of insulin secretion is manifest by impairment of the first-phase response to intravenous glucose. The terms glucotoxicity, lipotoxicity, and glucolipotoxicity are used to describe potentially responsible processes. Lipid initiated signaling also activates enzymes and mitochondrial metabolism of excess lipid substrates, both of which produce reactive oxygen species (ROS Apr 2, 2010 · Lipotoxicity is a major cause of insulin resistance and impaired beta cell function in type 2 diabetes mellitus and plays a central role in the accelerated CVD. Mar 1, 2021 · Reduction of β-cell mass and function is central to the pathogenesis of type 2 diabetes. Lipid toxicity refers to the damage caused by persistently high free f … Nov 26, 2021 · In fact, high concentrations of glucose and lipids have negative impacts on β-cell function and mass, phenomena referred to as glucotoxicity and lipotoxicity, respectively. Obese NZO mice are unable to compensate for the carbohydrate challenge by increasing insulin secretion or synthesising adequate amounts of insulin. The effect of oral treatment of allantoin (200, 400 and 800 mg/kg/day) for 8 weeks was evaluated by calculating the alteration in metabolic parameters, biochemical indicators, the oral glucose tolerance tests (OGTT) and hyperinsulinemic-euglycemic clamp tests Affiliation 1 Department of Geraeology, The First Affiliated Hospital, China Medical University, Shenyang 110001, China. Jan 30, 2009 · Thus alpha cells are resistant to gluco- and lipotoxicity, partly reflecting higher expression of genes involved in antioxidant defence. Regardless of the diabetes type, preservation and recovery of functional pancreatic beta cells stands as the biggest challenge in the Intense research has identified a number of genetic variants that may predispose to impaired B-cell function, but such predisposition can be precipitated and worsened by toxic effects of hyperglycaemia (glucotoxicity) and elevated levels of free fatty acids (lipotoxicity). , 2001 Enlarged fat cells in obese adipose tissue diminish capacity to store fat and are resistant to the anti-lipolytic effect of insulin. At 48 hours, neither lipotoxicity nor glucotoxicity had any effect on mtDNA and its transcription, but glucolipotoxicity significantly damaged mtDNA and decreased cytochrome b transcripts, and at 96 hours, glucotoxicity and glucolipotoxicity produced similar detrimental effects on mitochondrial damage. 47. Thus, the restoration of b-cell function is a long-sought goal in diabetes research. Dec 28, 2021 · Over the last decades, lipotoxicity and glucotoxicity emerged as established mechanisms participating in the pathophysiology of obesity-related type 2 diabetes in general, and in the loss of β-cell function in particular. In this review, we will focus on recent advances and current bottlenecks in the field of Feb 4, 2019 · Obesity and diabetes are often associated with lipotoxic conditions in multiple tissues. Apr 10, 2020 · Lipotoxicity is characterized by the ectopic accumulation of lipids in organs different from adipose tissue. There is an emerging role of AGEs and hypoxia in β-cell glucotoxicity. 7 mmol/l) for 48 h should also raise cytosolic LC-CoA. Lipo- and glucolipotoxicity have been studied for over 25 years. A number of hypotheses have been proposed to explain how these conditions induce beta cell dysfunction. Deciphering these molecular mechanisms of β-cell glucotoxicity is a mandatory first step toward the development of therapeutic strategies to protect β-cells and improve the functional β-cell mass in type 2 diabetes. 2337/diabetes. 1016/B978-84-8174-892-5. Although the detailed mechanisms underlying glucolipotoxicity remain unclear, they appear to be mediated by several intracellular metabolites affecting different Nov 24, 2009 · Intense research has identified a number of genetic variants that may predispose to impaired B-cell function, but such predisposition can be precipitated and worsened by toxic effects of hyperglycaemia (glucotoxicity) and elevated levels of free fatty acids (lipotoxicity). Nov 24, 2009 · Intense research has identified a number of genetic variants that may predispose to impaired B-cell function, but such predisposition can be precipitated and worsened by toxic effects of hyperglycaemia (glucotoxicity) and elevated levels of free fatty acids (lipotoxicity). Diabet Med , 26 : 1185-1192 [ PubMed ] [ Google Scholar ] [3] Dedoussis GV,Kaliora AC,Panagiotakos DB (2007). The result is the release of a host of inflammatory adipokines and excessive amounts of free fatty acids that promote ectopic fat deposition and lipotoxicity in muscle, liver, and pancreatic beta cells. 50016-4 Corpus ID: 82456560; The Lipotoxicity and Glucotoxicity Hypothesis in the Metabolic Syndrome and Type 2 Diabetes @inproceedings{Dimitriadis2005TheLA, title={The Lipotoxicity and Glucotoxicity Hypothesis in the Metabolic Syndrome and Type 2 Diabetes}, author={George D. Dec 1, 1998 · Culturing islets with high doses of glucose (16. Aug 22, 2019 · Glucotoxicity and lipotoxicity due to excess caloric intake and increased nutrient availability are the hallmarks of diabetes progress and disease complications [3,4,5,6]. Ceramides, ROS, inflammation, and ER stress signaling are intracellular mediators of β cell failure in this context. Type 2 diabetes mellitus is a disease characterized by persistent and progressive deterioration of glucose tolerance. 5. The preservation of <i>β</i> cell mass and function is one of the main goals of diabetes management und … At 48 hours, neither lipotoxicity nor glucotoxicity had any effect on mtDNA and its transcription, but glucolipotoxicity significantly damaged mtDNA and decreased cytochrome b transcripts, and at 96 hours, glucotoxicity and glucolipotoxicity produced similar detrimental effects on mitochondrial damage. These metabolic disturbances are a Chronic exposure to hyperlipidemia results in lipotoxicity in pancreatic β-cells, which contributes to progressive deterioration in β-cell function and mass and ultimately aggravation of type 2 Feb 24, 2021 · Until now, insulin-secreting β-cells have been thought to be directly affected by glucolipotoxicity. The premise is that chronically elevated glucose levels are toxic to β-cells, that elevated li … Jan 1, 2009 · Interventions that may prevent lipotoxicity in different target tissues, but in particularpancreatic beta-cell lipotoxicity, such as exercise, weight loss, and/or pharmacological therapies such as thiazolidinediones, hold the key to prevent diabetes in subjects genetically predisposed to T2DM and tackle the looming epidemic of the coming century. Effect of decreased glucotoxicity and/or lipotoxicity on β-cell function of isolated Nov 27, 2015 · In this study, we aimed to elucidate how the expression alterations of key β-cell factors are altered by the short-term selective alleviation of glucotoxicity or lipotoxicity. , 2001 Oct 11, 2018 · Persistent hyperglycemia presents glucotoxicity whereas continuous exposure to harmful FAs presents lipotoxicity. Our review describes the apoptosis of beta-cells induced by hyperglycemia, hyperlipidemia and both. Nonalcoholic fatty liver disease (NAFLD) is characterized by insulin resistance, which results in elevated serum concentration of free fatty acids (FFAs). demonstrated that inhibition of mitochondrial networking augments sensitivity to lipotoxicity . 2015. The underlying concept is that once the primary pathogenesis of diabetes is established, probably involving both genetic and environmental forces, hyperglycemi … Sep 13, 2020 · The premise is that chronically elevated glucose levels are toxic to β-cells, that elevated lipid levels in the form of circulating free fatty acids (FFA) also have toxic effects, and that the combination of the two, glucolipotoxicity, is particularly harmful. Nov 26, 2021 · In fact, high concentrations of glucose and lipids have negative impacts on β-cell function and mass, phenomena referred to as glucotoxicity and lipotoxicity, respectively. • Selective glucotoxicity reduction improves β-cell factors over pretreatment levels. Cette stratégie permettrait d’éviter ou retarder la perte structurelle et fonctionnelle progressive qui aboutit à un effondrement inéluctable de l’insulinosécrétion et, donc, à un échappement du contrôle glycémique. Both insulin resistance and impaired insulin secretion contribute to Jan 2, 2016 · Role of glucotoxicity and lipotoxicity in the pathophysiology of Type 2 diabetes mellitus and emerging treatment strategies. The detrimental effect of excessive glucose concentrations is referred to as 'glucotoxicity'. Lipotoxicity and glucotoxicity may both be implicated in the pathogenesis of type 2 diabetes. Raptis}, year={2005}, url={https://api Sep 11, 2020 · Taken together, all of these results provided direct evidence showing that TG could prevent the down-regulation of PDX1 expression and islet β-cells apoptosis induced by lipotoxicity and glucotoxicity by activating ERK signaling. The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. These results indicated that mitochondrial morphodynamics such as fusion and fission are involved in lipotoxicity in beta-cells and in the pathophysiology of type 2 diabetes. A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on … Aug 1, 2015 · Thus alpha cells are resistant to gluco- and lipotoxicity, partly reflecting higher expression of genes involved in antioxidant defence. mechanisms like glucotoxicity, lipotoxicity and glucolipotoxicity which include endoplasmic reticulum stress, mitochondrial dysfunction and oxidative stress. Resveratrol prevents renal lipotoxicity and inhibits mesangial cell glucotoxicity in a manner dependent on the AMPK-SIRT1-PGC1α axis in db/db mice Diabetologia . In his landmark 1994 paper, Roger Unger first recognized that lipid overload of pancreatic islets caused “lipotoxic” inhibition of pancreatic β-cell function (1). Feb 13, 2020 · The terms glucotoxicity, lipotoxicity, and glucolipotoxicity have been widely used, but there is some confusion as to what they mean precisely and which is most appropriate for a given situation. In this article we will provide an integrative view on the interrelation between decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations in type 2 diabetes. To overcome these difficulties, novel research methods and systems need to be established. Mar 3, 2020 · Lipo- and glucolipotoxicity have been studied for over 25 years. ROS and the activated JNK pathway stimulate the Foxo 1 induced nucleocytoplasmic translocation of PDX1, which leads to the reduction of PDX1 activity resulting in Aug 1, 2016 · The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. Insulin resistance has been shown to be present before the onset of chronic hyperglycemia, although the latter may contribute to aggravation of Sep 13, 2020 · The terms glucotoxicity, lipotoxicity, and glucolipotoxicity are used to describe potentially responsible processes. • Intestinal L cells undergo apoptosis under gluco/lipotoxicity like beta cells. Over time, both contribute to the Glucotoxicity or lipotoxicity leads to hyperglycemia and insulin secretion deﬁciency, which are important causes for the onset of type 2 diabetes mel-litus (T2DM). doi: 10. Nov 27, 2015 · Selective glucotoxicity reduction increases key pancreatic β-cell factors expression. In contrast, intestinal L cells, like beta cells, are prone to gluco- and lipotoxicity, possibly contributing to abnormalities of GLP-1 secretion in type 2 diabetes. Glucotoxicity and lipotoxicity are the forerunners of myocardial contractile dysfunction. 3. 6. 022 Corpus ID: 19278981; Differential molecular and cellular responses of GLP-1 secreting L-cells and pancreatic alpha cells to glucotoxicity and lipotoxicity. Feb 7, 2024 · Lipotoxicity of various long- and very long-chain saturated or unsaturated FFAs in human EndoC-βH1 beta-cells. Apr 23, 2023 · Cordycepin protects islet β-cells against glucotoxicity and lipotoxicity via modulating related proteins of ROS/JNK signaling pathway April 2023 Biomedicine & Pharmacotherapy 163:114776 Feb 6, 2019 · Dietary Lipids Contribute to the Development of Lipotoxicity. As predicted, citrate synthase Vmax was lowered and PFK Vmax was increased, both in a triacsin C-reversible fashion. However, under in vivo conditions, due to a series of physiological and metabolic communications associated with different tissues under the influence of dietary and 5. • Selective glucotoxicity reduction turns β-cell mass toward increase. Dec 1, 2015 · Corpus ID: 21438752; Glucotoxicity and lipotoxicity induced beta-cell apoptosis in type 2 diabetes mellitus @inproceedings{Kupsal2015GlucotoxicityAL, title={Glucotoxicity and lipotoxicity induced beta-cell apoptosis in type 2 diabetes mellitus}, author={Keerthi Kupsal and Saraswati Mudigonda and Kishore Kumar Gundapaneni and Mohini Aiyengar Tupurani and Rajesh Kumar Galimudi and Surekha Rani Mar 6, 2020 · The deleterious effects of chronically elevated free fatty acid (FFA) levels on glucose homeostasis are referred to as lipotoxicity, and the concurrent exposure to high glucose may cause synergistic glucolipotoxicity. Here we have used a sequential Jun 18, 2010 · Pancreatic β-cell lipotoxicity has also been proposed and shown under different experimental conditions to require the presence of hyperglycemia and that β-cell failure in T2DM is more closely related to glucotoxicity (ie, hyperglycemia being toxic to β cells and stimulating a downward spiral of insulin deficiency and worsening glucotoxicity Jun 2, 2019 · Then, we further demonstrated that hypericin elicited its protective effects against glucotoxicity and lipotoxicity in INS-1 cells by attenuating the reduction in pancreatic duodenal homeobox-1 (PDX1) expression and Erk activity. Dec 28, 2021 · These results revealed that, in the β-cell, lipotoxicity depends on glucotoxicity and that the cooperative effects of both, namely, glucolipotoxicity, relies on the fatty acid nature. Mar 3, 2020 · The concurrent exposure to high glucose (glucotoxicity) after the development of impaired glucose tolerance is considered to exert synergistic toxic effects with FFAs, which led to the concept of glucolipotoxicity as first proposed by Prentki and Corkey . Our results showed Hypericin showed preventive and therapeutic effects against HFHS-induced onset of type II diabetes in mice, and possesses great potential for development as an anti-diabetes drug in the future. We investigated whether Nov 24, 2010 · The dietary regimen dissociates the effects of obesity (lipot toxicity) from those of hyperglycaemia (glucotoxicity) in NZO mice and leads to reduced levels of beta cell-specific transcription factors and to apoptosis of the cells. Intense research has identified a number of genetic variants that may predispose to impaired B-cell function, but such predisposition can be precipitated and worsened by toxic effects of hyperglycaemia (glucotoxicity) and elevated levels of free fatty acids (lipotoxicity). Lipotoxicity is probably mediated by accumulation of a cytosolic signal derived from the fatty acid esterification pathway. Since hyperglycemia and hyperlipidemia commonly coexist in T2D and synergistically induce β-cell dysfunction and death, the term glucolipotoxicity is often preferred. Aug 15, 2024 · Allantoin reduces glucotoxicity and lipotoxicity in a type 2 diabetes rat model by modulating the PI3K and MAPK signaling pathways Author links open overlay panel Yao Zhao a , Ming Qiao b c , Xiaomei Wang a , Xinjie Luo a , Jianhua Yang b c , Junping Hu a c It is proposed that chronic hyperglycemia, independent of hyperlipidemia, is toxic for -cell function, whereas chronic hyper Lipotoxicity is deleterious only in the context of concomitant hyper glycemia. 47 While short-term exposure of β-cells to increased glucose concentration induces β-cell proliferation, long-term exposure suppresses β-cells, decreases glucose-stimulated insulin secretion (GSIS), and induces β-cell Feb 1, 2023 · Among these factors high levels of circulating FFA and glucose that induce lipotoxicity and glucotoxicity, respectively, through a mechanism that involves ROS generation, contribute to the development of non-alcoholic fatty liver disease associated with insulin resistance (IR), type II diabetes and cardiovascular disease (Yamagishi et al. Oct 1, 2020 · Un des objectifs majeurs, par ailleurs difficile à atteindre, dans la prise en charge du diabète de type 2 est de protéger la cellule β. Interventions that mobilise fat out of tissues (restriction of energy intake, thiazolidinediones, glucagon-like peptide-1 analogues) are likely to produce a durable reduction in Mar 6, 2020 · The concurrent exposure to high glucose (glucotoxicity) after the development of impaired glucose tolerance is considered to exert synergistic toxic effects with FFAs, which led to the concept of glucolipotoxicity as first proposed by Prentki and Corkey [4]. demonstrated that the adaptive UPR response was not activated in human β cells under chronic hyperglycemia and hyperlipidemia, suggesting that prolonged glucotoxicity and lipotoxicity may cause defective adaptive UPR response to resolve ER Stress . Lipotoxicity has roles in insulin re … Jan 1, 2005 · Lipotoxicity and glucotoxicity may play an important role in the pathogenesis of hyperglycemia and dyslipidemia in the Metabolic Syndrome and type 2 diabetes. 1016/j. Nov 25, 2012 · Finally, our recent evidence suggests that hypoxia may also be a new mechanism of β-cell glucotoxicity. A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on by glucose intolerance and insulin resistance Feb 1, 2011 · Glucotoxicity and lipotoxicity are important initiators of cardiovascular disease, abnormal energy metabolism, impaired contractile function, endothelial cell death, coronary heart disease and heart failure [20], [26]. In Mar 1, 2003 · For the purposes of this article, glucose toxicity of the islet is defined as nonphysiological and potentially irreversible β-cell damage caused by chronic exposure to supraphysiological glucose concentrations. Aug 1, 2015 · Knowledge on intestinal L cell susceptibility to gluco and lipotoxicity is limited. These results show shared selected functional and biochemical properties in beta-cells of so-called glucotoxicity and Aug 14, 2021 · Glucotoxicity or lipotoxicity leads to hyperglycemia and insulin secretion deficiency, which are important causes for the onset of type 2 diabetes mellitus (T2DM). Sep 29, 2015 · The characterized hyperglycemia of diabetic condition is also causing glucotoxicity and lipotoxicity along with insulin resistance which further resulted in apoptosis of β-cells (Kupsal et al Jun 12, 2016 · Glucotoxicity, lipotoxicity, and glucolipotoxicity engage endoplasmic reticulum stress and oxidative stress pathways that cause organ dysfunction and, in some cases, cell death . A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on by glucose intolerance and insulin resistance in tissues. Citation 1 Multiple factors are believed to be responsible for the progressive decline of the residual β-cell function. Jun 30, 2015 · PREVIEW. 2). In this study, we examined whether endogenous PACAP protects islet β-cells against the toxicities. INS-1 Aug 1, 2015 · Knowledge on intestinal L cell susceptibility to gluco and lipotoxicity is limited. In this review, we will focus on recent advances and current bottlenecks in the field Sep 25, 2020 · Hepatic lipotoxicity, due to massive FFAs flux from peripheral tissues or enhanced de novo lipogenesis, has been associated to NAFLD severity and comprises a variety of processes such as ER and Jul 15, 2018 · In addition, Wiederkehr et al. wncvxx gyavx psxr pzkg fio sybj mpdzeb ntvomm pnsmwykk ktvd

Glucotoxicity and lipotoxicity. live/y4s6/paladins-switch-control-settings.