Open Access Medical Books



Edited by Sarika Arora .

276 pages . 
Open Access .

Insulin resistance refers to reduced insulin action in metabolic and vascular target tissues, hence higher than normal concentration of insulin is required to maintain  normoglycemia and other actions of insulin, hence it may be considered as a  euglycemic pre-diabetic state. The growing incidence of insulin resistance and type 2  diabetes is seriously threatening human health globally. The development of insulin  resistance leads to many of the metabolic abnormalities associated with this syndrome.
The syndrome includes a cluster of clinical problems such as hypertension, dyslipidemia and obesity along with insulin resistance leading to a substantial  increase in cardiovascular risk. These patients tend to have impaired fasting plasma  glucose levels, which increase the prevalence of more atherogenic, small dense lowdensity  lipoprotein (LDL) particles.
During last decade several studies have been conducted to understand the mechanisms contributing to the state of insulin resistance. Insulin signalling pathways have been dissected in different insulin responsive tissues such as skeletal muscles, adipose tissues, fibroblasts as well as ovaries to elucidate the mechanism. These studies suggest a post receptor signalling defect where metabolic action of insulin is affected. The first chapter on Molecular mechanisms in Insulin resistance describes the insulin signaling pathways and broadly describes various mechanisms capable of producing an Insulin resistant state.
Metabolic regulation in cells is largely dependent on mitochondria, which play an important role in energy homeostasis by metabolizing nutrients and producing ATP.
Imbalance between energy intake and expenditure leads to mitochondrial dysfunction, characterized by a reduced ratio of energy production (ATP production) to respiration.
Genetic and environmental factors including diet, exercise, aging, and stress affect  both mitochondrial function and insulin sensitivity. Recently, it has been shown that  mitochondrial dysfunction is associated with insulin resistance in skeletal muscle, as  well as in other tissues, including liver, fat, heart, vessels, and pancreas. Thus, insulin  resistance caused in part by mitochondrial dysfunction may contribute to a common 
pathophysiologic etiology for many chronic diseases. Notably, SIRT3, a member of  sirtuins located in mitochondria, can regulate the function of mitochondrial proteins  via reversible posttranslational modification in response to metabolic stress.
Imbalanced acetylation status of mitochondrial proteins by decreased expression and activity of SIRT3 has been demonstrated as one of the factors in the pathogenesis of  insulin resistance in mice and human. The chapter by author Wang CH et al., describes  the effect of mitochondrial dysfunction on Insulin sensitivity.
Genetic and epidemiological studies strongly suggest that insulin resistance is, at least in part, genetically determined. However, the involved genes and their effective  variants are mostly unknown. The numerous genes have been suggested as a potential  candidate gene for insulin resistance. The chapter titled ‘Impact of genetic  polymorphisms on Insulin resistance’ by author Evrim Komurcu-Bayrak provides an  update on the genetics of Insulin resistance.
The mechanisms that underlie metabolic syndrome and its cardiometabolic consequences may very well vary between ethnicities. It has been a recurring theme  that the interactions between poor nutritional status, physical inactivity, and genetic  predisposition might contribute to the disparities in the prevalence and characteristics  of MetS and its components between ethnicities and the subgroups within. The  incidence, component characteristics and complications of the metabolic syndrome in  Puerto Ricans has been described in the chapter titled ‘The Metabolic Syndrome in  Hispanics - The Role of Insulin Resistance and Inflammation’ by author Dr Altieri et al.  wherein, they have highlighted the fact that the metabolic syndrome may be milder in  Puerto Rico than in the mainland United States because it is characterized by less  aggressive coronary artery disease and a relatively normal lipid profile.
The role of white adipose tissue (WAT) as an ordinary tissue responsible for lipid energy storage has been replaced due to studies that demonstrate the  central activity of WAT in lipid and glucose metabolism and its ability to secrete  factors with endocrine, paracrine and autocrine effects. For example, recent studies  suggest that pro-inflammatory and anti-inflammatory substances produced by WAT  contribute to the development of insulin resistance. The pro-inflammatory role of  adipose tissue and association of appetite regulatory peptides with Insulin resistance  have been covered in detail in the two chapters by authors Torres-Leal et al. and  Maria Orbetzova.
The next section focuses on the systemic effects of Insulin Resistance. The chapter titled ‘Cardiovascular and renal complications in obesity and obesity-related medical  conditions’ by Prof. Masuo and Lambert GV focuses on the sympathetic nervous  system activity and insulin resistance in metabolic and their role in the
etiopathogenesis of cardiovascular and renal complications in these patients. Another  chapter in the same section focuses on the Myocardial Insulin Resistance, wherein the  authors Eugene F du Toit and Daniel G Donner have beautifully described how  myocardial insulin resistance translates to compromised intracellular insulin  signalling and reduced glucose oxidation rates and adversely affects myocardial  mechanical function and tolerance to ischemia and reperfusion. The chapter on Ultrasonographic measurement of visceral fat by author Alempijevic T et al. describes how Ultrasonography can be used as a simple and reliable method for  measuring both subcutaneous and visceral fat in clinical settings.
Furthermore, the development of insulin resistance, is associated with increased tissue renin–angiotensin system activity and increasingly appears to be a nexus between  components of the syndrome. The chapter titled ‘Anti-hypertensive agents and their  benefits beyond blood pressure control’ by authors Nadya Merchant and Bobby V  Khan describe the effect of various antihypertensive agents especially angiotensin  receptor blockers on various biomarkers of insulin resistance.
The purpose of this book is to provide contemporary factual information on Insulin resistance. The articles in this issue provide a valuable overview of insulin resistance,  by integrating the recent advances which have occurred in various seemingly  disparate fields. Thus, I have relied on the expertise of several outstanding  contributors who are recognized authorities in their respective areas. I hope that this  book will serve as a valuable resource for all clinicians in the related fields and also for  the students.

Dr. Sarika Arora

Lady Hardinge Medical College,


Section 1 of the textbook : Molecular and Genetic Basis of Insulin Resistance 

Chapter 1 Molecular Basis of Insulin Resistance 
and Its Relation to Metabolic Syndrome 3 Sarika Arora

Chapter 2 Mitochondrial Dysfunction in Insulin Insensitivity 
and Type 2 Diabetes and New Insights for Their Prevention and Management 27 Chih-Hao Wang, Kun-Ting Chi, and Yau-Huei Wei

Chapter 3 Impact of Genetic Polymorphisms 
on Insulin Resistance 49 Evrim Komurcu-Bayrak

Section 2 of the textbook : Epidemiology of Insulin Resistance 

Chapter 4 The Metabolic Syndrome in Hispanics – 
The Role of Insulin Resistance and Inflammation 75 Pablo I. Altieri, José M. Marcial, Nelson Escobales, María Crespo and Héctor L. Banchs

Section 3 of the textbook : Role of Obesity and Neuropeptides in Insulin Resistance 

Chapter 5 Appetite Regulatory Peptides 
and Insulin Resistance 89 Maria Orbetzova

Chapter 6 Adipose Tissue Inflammation 
and Insulin Resistance 137 Francisco L. Torres-Leal, Miriam H. Fonseca-Alaniz, Ariclécio Cunha de Oliveira and Maria Isabel C. Alonso-Vale

Section 4 of the textbook : Systemic Effects of Insulin Resistance 

Chapter 7 Cardiovascular and Renal Complications in Obesity and 
Obesity-Related Medical Conditions: Role of Sympathetic Nervous Activity and Insulin Resistance 159 Kazuko Masuo and Gavin W. Lambert

Chapter 8 Myocardial Insulin Resistance: An Overview 
of Its Causes, Effects, and Potential Therapy 189 Eugene F. du Toit and Daniel G. Donner

Section 5 of the textbook : Diagnostic and Therapeutic Aspects in Insulin Resistance 

Chapter 9 Ultrasonographic Measurement of Visceral Fat 229 
Tamara Alempijevic, Aleksandra Pavlovic Markovic and Aleksandra Sokic Milutinovic

Chapter 10 The Effects of Antihypertensive Agents in Metabolic 
Syndrome – Benefits Beyond Blood Pressure Control 237 Nadya Merchant and Bobby V. Khan .

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Published by: younes younes - Friday, February 1, 2013


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