Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders

Identifying rare human metabolic disorders that result from a single-gene defect has not only enabled improved diagnostic and clinical management of such patients, but also has resulted in key biological insights into the pathophysiology of the increasingly prevalent metabolic syndrome. Insulin res...

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Main Authors: Rinki Murphy, Richard W. Carroll, Jeremy D. Krebs
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/920214
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author Rinki Murphy
Richard W. Carroll
Jeremy D. Krebs
author_facet Rinki Murphy
Richard W. Carroll
Jeremy D. Krebs
author_sort Rinki Murphy
collection DOAJ
description Identifying rare human metabolic disorders that result from a single-gene defect has not only enabled improved diagnostic and clinical management of such patients, but also has resulted in key biological insights into the pathophysiology of the increasingly prevalent metabolic syndrome. Insulin resistance and type 2 diabetes are linked to obesity and driven by excess caloric intake and reduced physical activity. However, key events in the causation of the metabolic syndrome are difficult to disentangle from compensatory effects and epiphenomena. This review provides an overview of three types of human monogenic disorders that result in (1) severe, non-syndromic obesity, (2) pancreatic beta cell forms of early-onset diabetes, and (3) severe insulin resistance. In these patients with single-gene defects causing their exaggerated metabolic disorder, the primary defect is known. The lessons they provide for current understanding of the molecular pathogenesis of the common metabolic syndrome are highlighted.
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spelling doaj-art-8c413e599374473d80ac1f32ac899c492025-08-20T02:09:13ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/920214920214Pathogenesis of the Metabolic Syndrome: Insights from Monogenic DisordersRinki Murphy0Richard W. Carroll1Jeremy D. Krebs2Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New ZealandEndocrine, Diabetes and Research Centre, Wellington Regional Hospital, Private Bag 7902, Newtown, Wellington 6021, New ZealandEndocrine, Diabetes and Research Centre, Wellington Regional Hospital, Private Bag 7902, Newtown, Wellington 6021, New ZealandIdentifying rare human metabolic disorders that result from a single-gene defect has not only enabled improved diagnostic and clinical management of such patients, but also has resulted in key biological insights into the pathophysiology of the increasingly prevalent metabolic syndrome. Insulin resistance and type 2 diabetes are linked to obesity and driven by excess caloric intake and reduced physical activity. However, key events in the causation of the metabolic syndrome are difficult to disentangle from compensatory effects and epiphenomena. This review provides an overview of three types of human monogenic disorders that result in (1) severe, non-syndromic obesity, (2) pancreatic beta cell forms of early-onset diabetes, and (3) severe insulin resistance. In these patients with single-gene defects causing their exaggerated metabolic disorder, the primary defect is known. The lessons they provide for current understanding of the molecular pathogenesis of the common metabolic syndrome are highlighted.http://dx.doi.org/10.1155/2013/920214
spellingShingle Rinki Murphy
Richard W. Carroll
Jeremy D. Krebs
Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders
Mediators of Inflammation
title Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders
title_full Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders
title_fullStr Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders
title_full_unstemmed Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders
title_short Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders
title_sort pathogenesis of the metabolic syndrome insights from monogenic disorders
url http://dx.doi.org/10.1155/2013/920214
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AT jeremydkrebs pathogenesisofthemetabolicsyndromeinsightsfrommonogenicdisorders