Diabetes & its Complications

Abstract

The Jiggly-Signal and Wiggly-Receptor Hypothesis: A Novel Perspective towards Pathogenesis and Aetiology of Metabolic Syndrome

Tavakolian Arjmand A

The galloping incidence and alarming prevalence of Metabolic Syndrome has put the human life on the edge of a public health catastrophe. Despite the full-blown epidemic and the daily growing list of clinical and biochemical manifestations of the syndrome, not much has been logically addressed with regard to a comprehensive pathogenesis and an integrated aetiology. What, currently, is discussed about metabolic syndrome is exactly the case of examining a huge elephant in the dark. We would like to shed a faint beam of light onto this perplexing issue, and puzzle out the neglected pieces inside the genuine picture of metabolic syndrome and carry the current concept one big step further. We believe that, the present health tsunamy is not merely a metabolic disorder, but also a real chaos at the level of molecular biology and inter-cellular dialogue; a state of metabolo-proteo-genomic disorder presenting itself as a host of metabolic derangements in addition to a generalized cellular dysapoptosis, causing cell senescence, cell swelling, derailed tissue remodeling and eventually a state of chronic oxidative stress. Opposite to dominant concept of over-feeding and related obesity as the initiating factor of metabolic syndrome, we believe that a worldwide ubiquitous environmental insult has led to a state of profound signal-receptor mal-engagement and misunderstanding with a strange pattern of acquired insulin resistance state, emerging explosively in late 1980s. We would like to suggest that, the centripetal obesity, as the stigma of metabolic syndrome, is the result of this newly emerged insulin resistance and the related compensatory hyperinsulinemia, not rather simplistically the cause of insulin resistance syndrome. In effect, one develops metabolic syndrome first, then becomes centrally obese, not the other way round. As a matter of easily understandable fact, in metabolic syndrome, a powerful lipolytic pairhormone which is GH/IGF-1, is taken over by an obsessed lipogenic substance, that is insulin. Comparable to blowing appearance of metabolic syndrome, we must look for a concurrent, concordant, eruptive and worldwide environmental intruder as the major aetiologic factor, an issue that will be addressed later on.

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