Uncoupling Protein 2 (UCP2): the Possible Missing Link in the Alteration of Glucose-induced Insulin Secretion by Fatty Acids PDF Download

Author: Nathalie Lameloise
Publisher:
ISBN:
Category :
Languages : en
Pages : 252

View

Book Description
Pour comprendre le mécanisme par lequel l'exposition long terme à des acides gras diminue la sécrétion d'insuline en réponse au glucose, nous avons cultivé des cellules INS-1 en présence d'oléate pendant 72 h. Nous avons démontré que les acides gras n'interféraient pas avec le métabolisme du glucose, mais qu'ils induisaient d'une part, une augmentation de l'expression de la protéine découplante, et d'autre part, qu'ils découplaient partiellement la mitochondrie. Les acides gras peuvent engendrer de nombreux effets dans ces cellules. C'est pourquoi nous avons surexprimé UCP2 au moyen d 'un système inductible qui a permis de mimer l'effet des acides gras sur la sécrétion d'insuline, mais pas sur le découplage de la mitochondrie.

Author: Narudee Kashemsant
Publisher:
ISBN:
Category :
Languages : en
Pages :

View

Book Description
The present study showed that UCP2 reduced ATP content without altering ATP synthase, thereby impairing GSIS. UCP2 increased insulin gene transcription but reduced proinsulin processing in the UCP2 overexpression model. Free fatty acid exposure of beta cells also caused impaired insulin processing, but this could not be directly attributed to UCP2 gene expression or correlated with reductions in ATP production. Lastly, high fat diet in wildtype mice was sufficient to impair GSIS and proinsulin processing but did not significantly increase UCP2 expression, or reduce intracellular ATP. From the UCP2 overexpression studies we conclude that induction of UCP2 can influence proinsulin processing, presumably by reducing intracellular ATP concentrations. Whether fatty acids influence proinsulin processing via their effects on UCP2 expression or activity was inconclusive. The five week dietary regime was sufficient to induce changes in glucose-stimulated insulin secretion and proinsulin processing but was insufficient to affect UCP2. This suggests that early changes in insulin secretion are not attributable to UCP2 expression, although effects on activity cannot be ruled out.

Author: Jamie W. (Jamie William) Joseph
Publisher: Library and Archives Canada = Bibliothèque et Archives Canada
ISBN: 9780612944947
Category :
Languages : en
Pages : 560

View

Book Description
A key event in insulin secretion from the pancreatic P-cell is glucose-stimulated mitochondrial production of adenosine triphosphate (ATP). Uncoupling protein-2 (UCP2) is localized to the inner mitochondrial membrane and plays a role as a "typical" uncoupler that modulates the efficiency of ATP production by catalyzing the translocation of protons across the mitochondrial membrane. This uncoupling reduces the protonmotive force that drives ATP synthase activity and thus reduces the ability of the beta-cell to increase ATP levels in response to glucose. The work presented here focuses on the role of UCP2 in the pancreatic beta-cell and the involvement of UCP2 in free fatty acid (FFA) induced beta-cell defects leading to type 2 diabetes. UCP2 was found to negatively regulate glucose-stimulated insulin secretion (GSIS). UCP2 expression is increased by FFAs suggesting a possible causal link between UCP2 and beta-cell defects associated with elevated FFA. Mice fed a high fat diet (HFD) have elevated UCP2 protein levels and blunted GSIS with no compensatory increase in beta-cell mass. Mice lacking UCP2 are resistant to the effects of a HFD on beta-cell function. HFD fed UCP2 ( -/- ) mice show no loss in GSIS and have an increase beta-cell mass. In order to assess the mechanism of enhanced beta-cell insulin secretion in mice lacking UCP2 an in vitro model was developed where isolated islets were exposed to 0.4 mM palmitate for 48 hours. The most proximal consequence of palmitate induced UCP2 levels appears to decrease glucose-stimulated changes in the mitochondrial membrane potential and this diminishes the downstream glucose-stimulated increase in both the ATP/ADP ratio and cytosolic Ca 2+. This leads to an attenuation of GSIS. UCP2 ( -/- ) mice have no loss in beta-cell glucose-stimulated hyperpolarization of the mitochondrial membrane potential and maintain their ability to secrete insulin in a glucose-dependent fashion. Therefore HFD fed mice or palmitate exposed islets lose their glucose sensitivity by a mechanism that likely involves increased UCP2. In addition, UCP2 may also modulate the oscillatory pattern of ATP production and thus oscillations in KATP channel activity, plasma membrane potential and insulin secretion. UCP2 is an important regulator of glucose sensing in the pancreatic beta-cell and upregulation of UCP2 in the pre-diabetic state could contribute to the loss of glucose responsiveness observed in obesity-related type 2 diabetes.

Author: Jonathan L Sessler
Publisher: Royal Society of Chemistry
ISBN: 1847552471
Category : Science
Languages : en
Pages : 431

View

Book Description
Anion recognition plays a critical role in a range of biological processes, and a variety of receptors and carriers can be found throughout the natural world. Chemists working in the area of supramolecular chemistry have created a range of anion receptors, drawing inspiration from nature as well as their own inventive processes. This book traces the origins of anion recognition chemistry as a unique sub-field in supramolecular chemistry while illustrating the basic approaches currently being used to effect receptor design. The combination of biological overview and summary of current synthetic approaches provides a coverage that is both comprehensive and comprehensible. First, the authors detail the key design motifs that have been used to generate synthetic receptors and which are likely to provide the basis for further developments. They also highlight briefly some of the features that are present in naturally occurring anion recognition and transport systems and summarise the applications of anion recognition chemistry. Providing as it does a detailed review for practitioners in the field and a concise introduction to the topic for newcomers, Anion Receptor Chemistry reflects the current state of the art. Fully referenced and illustrated in colour, it is a welcome addition to the literature.

Author: Ayse Basak Engin
Publisher: Springer
ISBN: 331948382X
Category : Science
Languages : en
Pages : 618

View

Book Description
Due to the resultant health consequences and considerable increase in prevalence, obesity has become a major worldwide health problem. “Obesity and Lipotoxicity” is a comprehensive review of the recent researches to provide a better understanding of the lipotoxicity-related mechanisms of obesity and the potential for the development of new treatment strategies. This book overviews the biochemical pathways leading to obesity-related metabolic disorders that occur subsequent to lipotoxicity. Chapters examine the deleterious effects of nutrient excess at molecular level including the cellular and molecular aspects of breast cancer, resistance to leptin, insulin, adiponectin, and interconnection between the circadian clock and metabolic pathways during high-fat feeding. “Lipotoxicity and Obesity” will be a useful resource for clinicians and basic science researchers, such as biochemists, toxicologists, immunologists, nutritionists, adult and pediatric endocrinologists, cardiologists, as well as students who are thought in this field.

Author: Helena Lenasi
Publisher: BoD – Books on Demand
ISBN: 1789842530
Category : Medical
Languages : en
Pages : 432

View

Book Description
The endothelium enables communication between blood and tissues and is actively involved in cardiovascular homeostasis. Endothelial dysfunction has been recognized as an early step in the development of cardiovascular diseases: respectively, endothelium represents a potential therapeutic niche with multiple targets. The purpose of the book is to point out some recent findings of endothelial physiology and pathophysiology emphasizing various aspects of endothelial dysfunction connected to the body's internal and external environment. While basic features of the endothelium are presented in an introductory chapter, the authors of the following 17 chapters have provided extensive insight into some selected topics of endothelial (dys)function. The book would hopefully be useful for anyone interested in recapitulating endothelial (patho)physiology and expanding knowledge of molecular mechanisms involved in endothelial dysfunction, relevant also for further clinical investigations.

Author: Omorogieva Ojo
Publisher: MDPI
ISBN: 3039217046
Category : Medical
Languages : en
Pages : 322

View

Book Description
The prevalence of diabetes is on the increase in the UK and worldwide, partly due to changes in lifestyle which predispose individuals to overweight and obesity. It is estimated that about 90% of the currently diagnosed adults have type 2 diabetes, and based on the World Health Organisation (WHO) report, about 422 million adults were living with diabetes in 2014 compared with 108 million in 1980; this condition caused about 1.5 million deaths in 2012. In the United States of America, it is estimated that about 30.3 million adults are living with diabetes, with a further 1.5 million new diabetes cases diagnosed every year, representing an increasing prevalence of this condition. Diabetes represents a major public health challenge, despite advances in technology and the pharmaceutical industry. These problems may be in the form of acute or long-term complications. Therefore, in order to attenuate the problems of diabetes, management strategies usually include lifestyle changes such as increased physical activity and dietary interventions. Studies which evaluate the role of nutrition in the management of type 2 diabetes often involve human and animal models as these approaches enable us to have a broader and more in-depth understanding of the condition. In some cases, diabetes may co-exist with other conditions, such as stroke, and these may present unique challenges with regard to nutritional interventions. This Special Issue aims to evaluate the risk factors associated with type 2 diabetes and the role of the diet in the management of people with this condition. This evidence is drawn from both human and animal studies.

Author: Sajal Chakraborti
Publisher: Springer Nature
ISBN: 9811382735
Category : Science
Languages : en
Pages : 596

View

Book Description
This book bridges the gap between fundamental and translational research in the area of heart disease. It describes a multidisciplinary approach, and demonstrates biochemical mechanisms associated with dysregulation of redox signaling, which leads heart disease. Presenting recent studies on improved forms of ROS scavenging enzymes; specific inhibitors for different ROS generating enzymes; and oxidant induced signaling pathways and their antagonists that allow subtle modulation of redox signaling, it also discusses the spatial and temporal aspects of oxidative stress in the cardiovascular system, which are of vital importance in developing better strategies for treating heart disease. Each chapter offers researchers valuable insights into identifying targets for drug development for different types of heart disease.

Author: Lawrence H. Lash
Publisher: Elsevier
ISBN: 1483218619
Category : Science
Languages : en
Pages : 527

View

Book Description
Methods in Toxicology, Volume 2: Mitochondrial Dysfunction provides a source of methods, techniques, and experimental approaches for studying the role of abnormal mitochondrial function in cell injury. The book discusses the methods for the preparation and basic functional assessment of mitochondria from liver, kidney, muscle, and brain; the methods for assessing mitochondrial dysfunction in vivo and in intact organs; and the structural aspects of mitochondrial dysfunction are addressed. The text also describes chemical detoxification and metabolism as well as specific metabolic reactions that are especially important targets or indicators of damage. The methods for measurement of alterations in fatty acid and phospholipid metabolism and for the analysis and manipulation of oxidative injury and antioxidant systems are also considered. The book further tackles additional methods on mitochondrial energetics and transport processes; approaches for assessing impaired function of mitochondria; and genetic and developmental aspects of mitochondrial disease and toxicology. The text also looks into mitochondrial DNA synthesis, covalent binding to mitochondrial DNA, DNA repair, and mitochondrial dysfunction in the context of developing individuals and cellular differentiation. Microbiologists, toxicologists, biochemists, and molecular pharmacologists will find the book invaluable.

Author: Thorsten Cramer
Publisher: Springer
ISBN: 3319421182
Category : Medical
Languages : en
Pages : 272

View

Book Description
This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications. Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.