Table Of ContentINSULIN RESISTANCE
Edited by Sarika Arora
Insulin Resistance
http://dx.doi.org/10.5772/3210
Edited by Sarika Arora
Contributors
Sarika Arora, Chih-Hao Wang, Kun-Ting Chi,, Yau-Huei Wei, Evrim Komurcu-Bayrak, Pablo I.
Altieri, José M. Marcial, Nelson Escobales, María Crespo, Héctor L. Banchs, Maria Orbetzova,
Francisco L. Torres-Leal, Miriam H. Fonseca-Alaniz, Ariclécio Cunha de Oliveira, Maria Isabel C.
Alonso-Vale, Kazuko Masuo, Gavin W. Lambert, Eugene F. du Toit, Daniel G. Donner, Tamara
Alempijevic, Aleksandra Pavlovic Markovic, Aleksandra Sokic Milutinovic, Nadya Merchant,
Bobby V. Khan
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Insulin Resistance, Edited by Sarika Arora
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Contents
Preface IX
Section 1 Molecular and Genetic Basis of Insulin Resistance 1
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 Epidemiology of Insulin Resistance 73
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 Role of Obesity and Neuropeptides
in Insulin Resistance 87
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
VI Contents
Section 4 Systemic Effects of Insulin Resistance 157
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 Diagnostic and Therapeutic Aspects
in Insulin Resistance 227
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
Preface
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 low-
density 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
X Preface
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.
Preface XI
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,
India
