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      Insulin and the Lung: Connecting Asthma and Metabolic Syndrome

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          Abstract

          Obesity, metabolic syndrome, and asthma are all rapidly increasing globally. Substantial emerging evidence suggests that these three conditions are epidemiologically and mechanistically linked. Since the link between obesity and asthma appears to extend beyond mechanical pulmonary disadvantage, molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin signaling provide mechanistic insight into the clinical evidence for the links between obesity, metabolic syndrome, and airway diseases, setting the stage for novel therapeutic avenues targeting these conditions.

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          Most cited references90

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          Convergence of Wnt, beta-catenin, and cadherin pathways.

          W Nelson (2004)
          The specification and proper arrangements of new cell types during tissue differentiation require the coordinated regulation of gene expression and precise interactions between neighboring cells. Of the many growth factors involved in these events, Wnts are particularly interesting regulators, because a key component of their signaling pathway, beta-catenin, also functions as a component of the cadherin complex, which controls cell-cell adhesion and influences cell migration. Here, we assemble evidence of possible interrelations between Wnt and other growth factor signaling, beta-catenin functions, and cadherin-mediated adhesion.
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            Obesity, metabolic syndrome, and cardiovascular disease.

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              Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies.

              Although obesity has been implicated as an asthma risk factor, there is heterogeneity in the published literature regarding its role in asthma incidence, particularly in men. To quantify the relationship between categories of body mass index (BMI) and incident asthma in adults and to evaluate the impact of sex on this relationship. Online bibliographic databases were searched for prospective studies evaluating BMI and incident asthma in adults. Independent observers extracted data regarding annualized asthma incidence from studies meeting predetermined criteria, within defined categories of normal weight (BMI or= 30). Data were analyzed by inverse-variance-weighted, random-effects meta-analysis. Stratified analysis between BMI categories and within sex was performed. Seven studies (n=333,102 subjects) met inclusion criteria. Compared with normal weight, overweight and obesity (BMI >or= 25) conferred increased odds of incident asthma, with an odds ratio (OR) of 1.51 (95% confidence interval [CI], 1.27-1.80). A dose-response effect of elevated BMI on asthma incidence was observed; the OR for incident asthma for normal-weight versus overweight subjects was 1.38 (95% CI, 1.17-1.62) and was further elevated for normal weight versus obesity (OR, 1.92; 95% CI, 1.43-2.59; p<0.0001 for the trend). A similar increase in the OR of incident asthma due to overweight and obesity was observed in men (OR, 1.46; 95% CI, 1.05-2.02) and women (OR, 1.68; 95% CI, 1.45-1.94; p=0.232 for the comparison). Overweight and obesity are associated with a dose-dependent increase in the odds of incident asthma in men and women, suggesting asthma incidence could be reduced by interventions targeting overweight and obesity.
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                Author and article information

                Journal
                J Allergy (Cairo)
                J Allergy (Cairo)
                JA
                Journal of Allergy
                Hindawi Publishing Corporation
                1687-9783
                1687-9791
                2013
                24 September 2013
                : 2013
                : 627384
                Affiliations
                1Center of Excellence for Translational Research in Asthma & Lung Disease, CSIR-Institute of Genomics and Integrative Biology, New Delhi 110007, India
                2Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA
                3Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
                4Research Center for Prevention and Health, Glostrup University Hospital, Glostrup 2600, Denmark
                Author notes
                *Anurag Agrawal: a.agrawal@ 123456igib.in

                Academic Editor: Balaram Ghosh

                Author information
                http://orcid.org/0000-0002-0340-5252
                Article
                10.1155/2013/627384
                3800560
                24204385
                d9d2806e-c31c-43ff-aef0-bb8b9be22955
                Copyright © 2013 Suchita Singh et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 March 2013
                : 8 August 2013
                : 21 August 2013
                Funding
                Funded by: http://dx.doi.org/10.13039/100000002 National Institutes of Health
                Award ID: HL088029
                Funded by: http://dx.doi.org/10.13039/100000002 National Institutes of Health
                Award ID: HL056470
                Categories
                Review Article

                Immunology
                Immunology

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