Insulin resistance can be regarded to be a cause, a consequence, a sustainer or a marker of the wider neuroendocrine dysfunction within which it occurs. In the final part of our series of reviews, we examine the systemic influences which operate within the metabolic syndrome: the endocrine system, the central nervous system and the immune system. We discuss strategies for integrating the array of information that is being gathered, in particular the need for computer simulation. We also advocate the need to move beyond the linear paradigm of ‘cause and effect’ and use causal networks to think about this system. We also discuss the need to understand the temperospatial organisation of the factors being studied. Finally, we draw together the data, concepts and hypotheses we have reviewed over the course of these four articles.
Keywords: Metabolic syndrome, hypertension, obesity, insulin resistance, epidemiology, cortisol, hypothalamo-pituitaryadrenal axis, insulin, insulin signalling, hyperinsulinemia
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