Microcirculation and Insulin Resistance


by

Nicolas WIERNSPERGER

DOI: 10.2174/97816080505741090101
eISBN: 978-1-60805-057-4, 2009
ISBN: 978-1-60805-683-5

  
  


Indexed in: Scopus

Insulin resistance is the main factor involved in the occurrence of the metabolic syndrome and later development of type2 diabetes. D...[view complete introduction]
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Table of Contents

Preface , Pp. i-ii (2)

Nicolas WIERNSPERGER, Eliete BOUSKELA and L. Guilherme KRAEMER-AGUIAR

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Contributors , Pp. iii-iv (2)

Nicolas WIERNSPERGER, Eliete BOUSKELA and L. Guilherme KRAEMER-AGUIAR

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Microcirculation: Structural and Functional Specificities , Pp. 1-13 (13)

Eliete Bouskela, Daniel Bottino and Nicolas Wiernsperger

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Techniques to Measure Microcirculatory Parameters in Insulin Resistant States in Humans , Pp. 14-30 (17)

Luiz Guilherme Kraemer-Aguiar and Eliete Bouskela

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Microvascular Dysfunction in Insulin Resistance , Pp. 31-40 (10)

Jefferson C. Frisbee and Robert W. Brock

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Microvascular Dysfunction: Potential Role in the Pathogenesis of Obesity-Associated Hypertension and Insulin Resistance , Pp. 41-54 (14)

Erik H Serne, Rick I Meijer, Michiel P de Boer, Renate T de Jongh, Richard G IJzerman, Wineke Bakker, Etto C Eringa and Etto C Eringa

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Inflammatory Responses to Obesity and Insulin Resistance , Pp. 55-69 (15)

Georg Singer and D. Neil Granger

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Oxidative Stress and Microvascular Function in Insulin- Resistant States , Pp. 70-84 (15)

P. Rosen and R. Rosen

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Microalbuminuria and Insulin Resistance , Pp. 85-90 (6)

Borje Haraldsson

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Importance of Microparticles in Microcirculation and Diseases , Pp. 91-98 (8)

Maria Carmen Martinez and Ramaroson Andriantsitohaina

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Hemorheology in Insulin Resistance , Pp. 99-106 (8)

Jean-Frederic Brun, Emmanuelle Varlet-Marie, Ikram Aloulou, Mathieu Sardinoux, Eric Raynaud de Mauverger and Jacques Mercier

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Post-Myocardial Infarction Insulin Resistance: A Sentinel Role for the Muscle Microcirculation , Pp. 107-118 (12)

David C. Poole and Timothy I. Musch

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Is Defective Microcirculation Responsible for Insulin Resistance? PART 1: Microvascular Dysfunction and Insulin Resistance are Linked: Evidences from Clinical Observations , Pp. 119-139 (21)

Nicolas Wiernsperger

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Is Defective Microcirculation Responsible for Insulin Resistance? PART 2. Insulin and Microcirculation: Physiology and Pathophysiology , Pp. 140-155 (16)

Nicolas Wiernsperger

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Is Defective Microcirculation Responsible for Insulin Resistance? PART 3. Microvascular Defects Potentially Leading to Insulin Resistance , Pp. 156-167 (12)

Nicolas Wiernsperger

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Preface

Insulin resistance (IR) is a common basis for many acute or long-term pathologies. Although it is best known in the area of cardiometabolic diseases because of the worldwide burden of obesity and diabetes, IR is observed in the vast majority of pathological situations. Very intensive research over the last 20 years has unravelled the defective mechanisms responsible for inadequate insulin receptor signaling and glucose transport and storage. However, the causal mechanisms producing IR are still elusive

Many factors are known to lead to IR which, in view of the great variety of diseases exhibiting IR, suggests that they converge toward a common point from which tissue IR is initiated. The fact that by far not all IR states worsen toward diabetes indicates that this element may be only transiently disturbed by acute pathologies and repaired. Conceivably, those patients unable to recover over a given period of time experience a delayed development of the deleterious consequences of IR such as cardiovascular diseases or metabolic syndrome or diabetes.

Since 1) the main physiological role of insulin is to supply the skeletal muscle cells with the excessive glucose in postprandial periods and 2) capillary flow is ultimately the key determinant of nutrient delivery to cells, we would like to expose and discuss a new concept stating that microcirculation and insulin sensitivity are linked such as to function both ways. In this book, we describe many puzzling observations according to which IR and microvascular dysfunction are usually found concomitantly, well before cardiometabolic diseases are clinically observable; this parallel can even be seen in normal, healthy populations within a normal range of insulin sensitivity. This means that microvascular dysfunction could be a cause of IR and thus represent the guilty element underlying IR in so many clinical disorders.

Bouskela et al. present a concise but complete overview of the multiple specificities of micro-vs macrocirculation. It is shown how closely structure and regulation of microvessels correlate with the functions of individual typical segments of the microvascular tree (arterioles, capillaries, venules). In a complementary chapter, Kraemer-Aguiar and Bouskela detail and critically review the various techniques used to measure endothelial function and microvascular reactivity in humans. Indeed, most information is only partly or not at all derived from the microvasculature. These informations are of utmost importance for sorting the plethoric amount of published data in this field, as also thoroughly discussed in the first part of the last book chapter. Frisbee and Brock review data on microcirculation and IR by comparing IR in the presence vs absence of obesity in rodents. They give detailed information on the impact of IR on dilator and constrictor responses as well as capillary perfusion, and highlight the integrated way microcirculation functions. The clinical aspect of IR and microvascular dysfunction is the subject of the chapter by Serné et al, focusing on obesity and hypertension, two major components of the metabolic syndrome. In a very in-depth analysis of a broad series of consequent investigations, they delineate how microvascular and metabolic factors are linked and they particularly shed light on the links between adipose tissue and the microvasculature. Some selected mechanistic aspects are more specifically developed in a series of chapters because of their recognized importance for microcirculation in pathological circumstances. Adipose tissue being a major source of inflammatory factors, Singer and Granger deal with the impact cytokines may have on the microvasculature and how the subsequent defects underlie cardiovascular pathologies affecting obese patients. Low-grade inflammation is doubtless one main common denominator between the vast majority of diseases characterized by IR. The endothelium, playing such prominent roles in vasomotricity and nutrient transfer, is damaged by inflammation as well as by oxidative stress. Rösen and Rösen provide an overview on the origins, mechanisms and consequences of oxidative stress in microvessels. One typical defect characterizing endothelial damage is microalbuminuria; as developed by Haraldsson, microalbuminuria is not only a local renal phenomenon but reveals a more generalized endothelial dysfunction throughout the body, making this parameter an interesting early marker in clinical settings. Martinez and Andriantsitohaina present a very innovative aspect of microcirculation, namely the recently discovered existence of circulating microparticles. They have different origins and can induce deleterious as well as beneficial effects; although still relatively little is known about microparticles, we felt that this exciting new player was worth being developed in the present analysis. A cardinal feature in capillary perfusion is evidently the flow behaviour of blood, i.e. hemorheology. Hemorheology deals with aspects which have a major, but mostly very local importance, i.e. the physical properties of flowing blood such as viscosity (whole blood, plasma) and erythrocyte deformability/aggregation. While it is easily comprehensible that disturbed red blood cell behavior impairs flow through tiny capillaries, it is less recognized that whole blood or plasma viscosity have major consequences too and, interestingly, they are also very early seen in these IR pathologies as exposed by Brun et al.

In the last chapter, divided in three distinct parts, Wiernsperger first critically describe the multiple confounding factors in epidemiological, hemodynamic and metabolic investigations which are likely to severely bias data interpretation; subsequently a broad description is given of the many different diseases characterized by microvascular defects. Of paramount interest are the many studies on healthy first degree relatives of parents with diabetes or cardiovascular diseases, as well as even normal healthy subjects in which the very early appearance of microvascular disturbances strongly suggests that they can be inherited. Part 2 addresses the specific emodynamic effects of insulin itself in the microcirculation and discusses the data under consideration of their physiological pertinence. In particular it is shown that very small increments in plasma insulin such as they occur at the very beginning of meals may be crucial to maximize opening of the microvascular bed in skeletal muscle for supply and storage of excess prandial glucose. Part 3 deals with an analysis of possible mechanisms whereby very early microvascular defects in life might impair proper microflow and thus interfere with the normal handling of glucose by insulin, i.e. induce IR.

This book is consciously prospective and proposes a concept based on physiological reasoning and established clinical and pathophysiological observations; by no means does this concept claim to be unique and valid for all situations. We are, however, convinced that there is sufficient available argumentation to deserve further fundamental and clinical research in order to definitively confirm or deny the correctness of what we believe is actually a “solid hypothesis”, namely that microvascular dysfunction can trigger insulin resistance.

Nicolas WIERNSPERGER, Ph.D.
Editor

Eliete BOUSKELA, M.D., Ph.D
L.Guilherme KRAEMER-AGUIAR, M.D
Co-Editors

List of Contributors

Editor(s):
Nicolas WIERNSPERGER
INSERM U870, INSA Lyon
France




Co-Editor(s):
Eliete Bouskela
State University of Rio de Janeiro
Brazil


Luiz Guilherme Kraemer-Aguiar
State University of Rio de Janeiro
Brazil




Contributor(s):
Ramaroson Andriantsitohaina Ph.D.

Faculté de Médecine, Université d’Angers
INSERM U771, CNRS UMR
France


Wineke Bakker Ph.D.
Laboratory for Physiology
Institute for cardiovascular research, VU medical Centre
Amsterdam
The Netherlands


Daniel Bottino Ph.D.
Laboratorio de Pesquisas em Microcirculaçao
Centro Biomedico, Uniersidade do Estado do
Rio de Janeiro
Brazil


Eliete Bouskela M.D., Ph.D.
Professor, Laboratorio de Pesquisas em Microcirculaçao
Centro Biomedico, Universidade do Estado do Rio de Janeiro
Rio de Janeiro
Brazil


Robert W. Brock Ph.D.
Dept of Physiology and Pharmacology
Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center
Morgantown
WV
USA


Jean-Frederic Brun Ph.D.
INSERM ERI25 Muscle et Pathologies
Service Central de Physiologie Clinique, CERAMM, CHU Lapeyronie
Montpellier
France


Michiel P. de Boer M.D.
Dept of Internal Medicine
Institute for Cardiovascular Research, VU Medical Centre
Amsterdam
The Netherlands


Renate T. de Jongh M.D., Ph.D.
Dept of Internal Medicine
Institute for Cardiovascular Research, VU Medical Centre
Amsterdam
The Netherlands


Etto C. Eringa Ph.D.
Laboratory for Physiology
Institute for cardiovascular research, VU medical Centre,
Amsterdam
The Netherlands


Jefferson Frisbee
Dept of Physiology and Pharmacology, Center for Cardiovascular and Respiratory Sciences
West Virginia University Health Sciences Center
Morgantown
WV
USA


D. Neil Granger Ph.D.
Dept of Molecular and Cellular Physiology
LSU Health Sciences Center
Shreveport
LA
USA


Börje Haraldsson Ph.D.
Dept of Molecular and Clinical Medicine,Nephrology
Institute of Medicine , University of Gothenburg
Gothenburg
Sweden


Richard G IJzerman M.D., Ph.D.
Dept of Internal Medicine
Institute for Cardiovascular Research, VU Medical Centre
Amsterdam
The Netherlands


L. Guilherme Kraemer-Aguiar M.D., Ph.D.
Laboratorio de Pesquisas em Microcirculaçao, Centro Biomedico
Universidade do Estado do Rio de Janeiro
Rio de Janeiro
Brazil


Maria Carmen Martinez Ph.D.
Faculté de Médecine, Université d’Angers
INSERM U771, CNRS UMR 6214
France


Rick I. Meijer M.D.
Dept of Internal Medicine
Institute for Cardiovascular Research, VU Medical Centre
Amsterdam
The Netherlands


Jacques Mercier M.D., Ph.D.
INSERM ERI25 Muscle et Pathologies
Service Central de Physiologie Clinique, CERAMM, CHU Lapeyronie
Montpellier
France


Timothy I Musch Ph.D.
Depts of Kinesiology, Anatomy and Physiology
Manhattan
Kansas
USA


David C. Poole Ph.D.
Depts of Kinesiology, Anatomy and Physiology
Manhattan
Kansas
USA


Eric Raynaud de Mauverger Ph.D.
INSERM ERI25 Muscle et Pathologies
Service Central de Physiologie Clinique, CERAMM, CHU Lapeyronie
Montpellier
France


Peter Rösen Ph.D.
German Diabetes Research Center,
Dusseldorf
Germany


Renate Rösen Ph.D.
Institute of Pharmacology, University of Cologne
Germany


Mathieu Sardinoux Ph.D.
INSERM ERI25 Muscle et Pathologies
Service Central de Physiologie Clinique, CERAMM, CHU Lapeyronie
Montpellier
France


Eric H. Serné M.D., Ph.D.
Dept of Internal Medicine
Institute for Cardiovascular Research, VU Medical Centre
Amsterdam
The Netherlands


Georg Singer M.D.
Dept of Pediatric Surgery
Medical University of Graz
Graz
Austria


Emmanuelle Varlet-Marie Ph.D.
Laboratoire de Biophysique et Bioanalyses
Faculté de Pharmacie, Université de Montpellier I
Montpellier
France


Nicolas F. Wiernsperger Ph.D.
NSERM U870, INSA Lyon
Villeurbanne
France




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