Impaired Incretin Effects In Type 2 Diabetes

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Impaired Incretin Effects In Type 2 Diabetes

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Author : Zhanfang Kang
language : en
Publisher:
Release Date : 2012

Impaired Incretin Effects In Type 2 Diabetes written by Zhanfang Kang and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with Glucagon-like peptide 1 categories.

Incretin-based drugs, such as glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. liraglutide and exenatide) and dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. sitagliptin and vildagliptin), which inhibit degrading intact GLP-1, have been a novel therapeutics for the treatment of type 2 diabetes. Type 2 diabetes mellitus (T2DM) is associated with reduced incretin effects. The underlying mechanism, however, is not well understood.

Handbook Of Incretin Based Therapies In Type 2 Diabetes

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Author : Stephen Gough
language : en
Publisher: Springer
Release Date : 2016-06-07

Handbook Of Incretin Based Therapies In Type 2 Diabetes written by Stephen Gough and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-06-07 with Medical categories.

This concise handbook provides an overview of incretin-based therapies and guidance for incorporating them into the treatment of type 2 diabetes. Chapters include landmark clinical trials and international treatment guidelines in order to update readers with all major advances in the field. An ideal resource for medical professionals that treat patients with type 2 diabetes in hospital and clinical settings.

The Influence Of Good Glycaemic Control On The Impaired Effect And Secretion Of The Incretin Hormones In Patients With Type 2 Diabetes Mellitus

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Author : Patricia Maria Verdugo Højbjerg
language : en
Publisher:
Release Date : 2007

The Influence Of Good Glycaemic Control On The Impaired Effect And Secretion Of The Incretin Hormones In Patients With Type 2 Diabetes Mellitus written by Patricia Maria Verdugo Højbjerg and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007 with categories.

Introduction To Biological And Small Molecule Drug Research And Development

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Author : Matthew P. Coghlan
language : en
Publisher: Elsevier Inc. Chapters
Release Date : 2013-05-07

Introduction To Biological And Small Molecule Drug Research And Development written by Matthew P. Coghlan and has been published by Elsevier Inc. Chapters this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-05-07 with Science categories.

The increasing global prevalence of type 2 diabetes represents a significant burden of disease for afflicted patients and for health care systems. In the developed world poorly controlled diabetes is the leading cause of non-traumatic amputation, blindness and end-stage renal disease requiring dialysis and kidney transplant. Additionally, diabetes represents a significant risk factor for the development of cardiovascular disease with its associated morbidity and premature death. Currently available glucose lowering drugs used to treat type 2 diabetes do not impede progression of the disease. Therefore, as the disease progresses these agents rapidly lose efficacy, first as monotherapy and then in combination, resulting in poorly controlled disease. Clearly, there is a significant need for novel glucose lowering drugs for type 2 diabetes that will deliver sustained efficacy over several years by impeding disease progression. Such agents would reduce the risk of developing the microvascular complications of diabetes that ultimately result in amputation, blindness and kidney transplant. Novel glucose lowering drugs should ideally also exhibit a positive impact on the increased cardiovascular risk associated with diabetes. The incretin-based therapies first entered the market in the mid 2000’s and were heralded for their potential to impede progression of type 2 diabetes and to reduce cardiovascular risk. Through mimicking the actions of the gut incretin hormone GLP-1, these drugs had been shown to lower blood glucose in clinical trials by potentiating glucose stimulated insulin secretion from pancreatic β-cells. Moreover, data from preclinical rodent disease models and isolated human pancreatic islets suggested that these novel agents could preserve pancreatic β-cell function and thus impede disease progression. Further preclinical and clinical data supported the notion that these drugs could also aid blood glucose control by suppressing glucagon secretion, slowing gastric emptying and by suppressing appetite. The incretin-based drugs have potential to reduce cardiovascular risk through their ability to reduce body weight, blood pressure and atherogenic blood lipids. This chapter will review the incretin-based therapies and consider what impact these new drugs have made to date in the pharmacotherapy of type 2 diabetes. The incretin-based therapies are of particular relevance to this book as this class of drugs is composed of two sub-classes, injectable peptide drugs and oral small molecule drugs. The similarities and differences between these small molecule and peptide drugs are described.

Incretin Based Therapies

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Author : Sanjay Kalra
language : en
Publisher: JP Medical Ltd
Release Date : 2013-03-31

Incretin Based Therapies written by Sanjay Kalra and has been published by JP Medical Ltd this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-03-31 with Medical categories.

Incretins are a group of gastrointestinal hormones that cause an increase in the amount of insulin released from cells in the pancreas after eating. Incretin based drugs are used to control blood sugar levels in the management of diabetes. This book is a concise guide to incretin based therapy. Beginning with an introduction to the history and physiology of incretins, the following sections examine the clinical pharmacology of GLP-1 Analogues and DPP-4 Inhibitors, the pleiotrophic effects of incretins and comparative pharmacology. Each section integrates science with practical therapeutic guidance for clinicians involved in the management of diabetes. The final chapter discusses the future of incretin therapies, including non-diabetic usage and combination therapy. Key Features Concise overview of incretin based therapy for the management of diabetes Guides clinicians step by step through the history and pharmacology of various molecules Integrates science with practical therapeutic guidance Includes chapter on the future of incretin therapy

The Entero Insular Axis

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Author : Werner Creutzfeldt
language : en
Publisher: S. Karger AG (Switzerland)
Release Date : 1980

The Entero Insular Axis written by Werner Creutzfeldt and has been published by S. Karger AG (Switzerland) this book supported file pdf, txt, epub, kindle and other format this book has been release on 1980 with Medical categories.

Type 2 Diabetes Mellitus

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Author : M. Serrano Ríos
language : en
Publisher: Elsevier España
Release Date :

Type 2 Diabetes Mellitus written by M. Serrano Ríos and has been published by Elsevier España this book supported file pdf, txt, epub, kindle and other format this book has been release on with categories.

1: Classification of Diabetes Mellitus: Criteria for Diagnosis. -- 2: The General Epidemiology of Type 2 Diabetes Mellitus. --New Insights on Prediabetes. -- 3: Vascular Reactivity in Diabetes Mellitus. -- 4: The Molecular and Genetic Basis of Type 2 Diabetes Mellitus. -- 5: Gene-Environment Interactions Predisposing to Type 2 Diabetes Mellitus. -- 6: Regulation of homeostasis: Glucose and other Substrates. -- 7: From Insulin Action to hormonal Resistance. --Old to Recent Molecular Mechanisms. -- 8: Type 2 Diabetes: Insulin Resistance vs. --Beta-Cell Defect. -- 9: Natural history of Type 2 Diabetes and Macrovascular Disease. -- 10: Microvascular Complications in Type 2 Diabetes. -- 11: Diabetic Neuropathy and Foot Disease. -- 12: Hypertension in Type 2 Diabetes Mellitus. -- 13: Dyslipidemia in Type 2 Diabetes Mellitus. -- 14: Diabetes Mellitus Prevention. -- 15: Present Recommendations in Type 2 Diabetes Mellitus Treatment. -- 16: New Pharmacological Approaches in Type 2 Diabetes Mellitus. -- 17: Relevant Outcomes in Type 2 Diabetes.

Developmental Biology Of Gastrointestinal Hormones

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Author : M. Wabitsch
language : en
Publisher: Karger Medical and Scientific Publishers
Release Date : 2017-08-16

Developmental Biology Of Gastrointestinal Hormones written by M. Wabitsch and has been published by Karger Medical and Scientific Publishers this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-08-16 with Medical categories.

The gut not only represents the largest endocrine organ of the human body but is also profoundly involved in the control of metabolism through peptide hormones. Therefore, gastrointestinal hormones are acting via autocrine, paracrine, and classical endocrine pathways and regulate e.g. digestion, hunger, and satiety. Furthermore, they are important regulators of body weight, growth, and glucose metabolism, as well as of mood and behavior. Physicians and scientists in the field of pediatric endocrinology and diabetes, as well as in pediatric gastroenterology, require an extensive understanding of the origin of enteroendocrine cells, factors controlling their differentiation, hormone gene expression, secretion, function and, finally, the complex interaction with other organs, especially the central nervous system. In order to meet these needs, experts in the field have written up-to-date, comprehensive, and illustrated reviews presenting the current knowledge in the field of gastrointestinal endocrinology with a pediatric view. Those reviews comprise this latest volume of Endocrine Development.

Novel Incretin Based Therapies For Type 2 Diabetes And Obesity

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Author : Barry Kerr
language : en
Publisher:
Release Date : 2011

Novel Incretin Based Therapies For Type 2 Diabetes And Obesity written by Barry Kerr and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.

Gut peptides including glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-l (GLP-I), and oxyntomodulin (Oxm) act to regulate glucose homeostasis, insulin secretion, bodyweight and satiety. However, clinical development has been hindered by rapid enzymatic degradation followed by renal clearance. This thesis evaluates the biological activities of these peptides, and exploits various chemical modifications / approaches to generate novel mimetics with therapeutic potential for type 2 diabetes and obesity. Acylation of Lys37 in GIP with C-14 fatty acid (myristate) afforded dipeptidylpeptidase-IV (DPP-IV) resistance and significantly enhanced in vitro cAMP production and insulin secretion. Furthermore, administration of N- AcGIP(Lys37 MYR) resulted in markedly improved glucose homeostasis and insulin-release in obese diabetic (ob/ob) mice. Once-daily administration of the DPP- IV resistant GIP analogue, GIP[mPEG], decreased non-fasting plasma glucose concentrations, increased insulin concentrations and improved glycaemic and insulin responses to a glucose load in mice with age-related glucose intolerance. These data clearly demonstrate the utility of stable analogues of GIP for treatment of obesity- diabetes. The GLP-l mimetic, Liraglutide, lacking the y-glutamyl linker (Lira-yGlu) demonstrated equi-potent DPP-IV resistance, cAMP production and insulin secretion compared with Liraglutide. In vivo, Lira-yGlu and Liraglutide significantly lowered plasma glucose in fasted mice. Twice-daily administration of either GLP-l analogue decreased food intake and plasma glucose concentrations, whilst increasing plasma insulin, and improving glucose tolerance and insulin sensitivity. These data indicate lack of requirement of y-glutamyl linker together with acylation for generation of long-acting incretin mimetics. Evaluating the effects of a an overnight preparation of Liraglutide and N- AcGIP(Lys37Myr) (Lira-AcGIP - mixed together and incubated for 12h) revealed improved acute glucose tolerance and insulin responses compared to a simple combination (immediate mixture). Furthermore, daily administration of the Lira- AcGIP preparation lowered bodyweight, decreased food intake, plasma glucose and insulin concentrations in ob/ob mice, as well as enhancing glucose tolerance, insulin response to glucose and insulin content. These data indicate the possibility of using combination therapy with stable GLP-l and GIP mimetics for treatment of type 2 diabetes. Oxm analogues, (0-Ser2)Oxm and (0-Ser2)Oxm[mPEG-PAL] exhibited DPP- IV stability, with equi-potent in vitro cAMP production and insulin secretion. In the presence of specific antagonists, cAMP production was reduced in GLP-l and glucagon receptor transfected cells, consistent with actions of dual receptor agonism. In acute studies, (0-Ser2)Oxm and (0-Ser2)Oxm[mPEG-PAL] exhibited glucoregulatory and anorexigenic properties with (0-Ser2)Oxm[mPEG-PAL] demonstrating more potent actions. Once-daily administration of (0- Ser2)Oxm[mPEG-PAL] decreased food intake, bodyweight and plasma glucose concentrations and increased insulin concentrations in ob/ob mice whilst improving glucose tolerance, insulin response to glucose and plasma lipid profiles. The N-terminal domain of GIP plays an important role in regulating its biological activity. Examining several novel N-terminally truncated forms of GIP revealed that GIP(8-42) exhibited reduced cAMP levels compared to native hormone whilst inhibiting GIP-induced cAMP production. In ob/ob mice, GIP(8-42) increased plasma glucose concentrations compared to the glucose-lowering action of native GIP. When GIP(8-42) was co-administered with GIP it countered the ability of the native hormone to lower plasma glucose and increase insulin concentrations. These data demonstrate the importance of the N-terminal of GIP in regulating bioactivity. Collectively, these data illustrate chemical modifications / approaches to improve the biological efficacy of GIP, GLP-l and Oxm. The use of smaller moieties to offset enzymatic degradation and renal clearance offer improved efficacy potentially due to reduced steric hindrance compared to currently available incretin therapies. In addition, incretin preparations and the dual role of Oxm may offer targeted 'smart therapy' for both obesity and type 2 diabetes. Hopefully this thesis will aid the development of pharmaceutical agents and subsequent clinical studies that will ultimately improve the lives of people suffering from type 2 diabetes and obesity.

Diabetes Epidemiology Genetics Pathogenesis Diagnosis Prevention And Treatment

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Author : Enzo Bonora
language : en
Publisher: Springer
Release Date : 2018-10-23

Diabetes Epidemiology Genetics Pathogenesis Diagnosis Prevention And Treatment written by Enzo Bonora and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-10-23 with Medical categories.

This book provides the reader with comprehensive information on the epidemiology, etiology, pathogenesis, pathophysiology, clinical features, prevention, and treatment of diabetes with the aim of empowering health care providers in their daily battle against the disease. Diabetes has been identified by WHO and the United Nations as a medical emergency because of the increase in its global prevalence, which may reach one billion in three to four decades if the trend remains unchanged. Despite improved care that is helping to prolong life, diabetes impacts substantially on the quality of life of those affected and kills or disables several million people each year. The disease is systemic because all organs, tissues, and cells suffer in the presence of hyperglycemia and are damaged by the diabetic milieu. Unfortunately, most patients with diabetes will consequently experience chronic diabetic complications. This book, combining basic science with a practical clinical orientation, will be of value for all physicians and nurses who care for patients with diabetes.