38
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Circulating levels of irisin in middle-aged first-degree relatives of type 2 diabetes mellitus — correlation with pancreatic β-cell function

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Irisin is a novel myokine secreted in response to peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) activation through exercise. The first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM) patients bear a lifetime risk for developing T2DM, especially after 40 years old. However, the circulating irisin levels in middle-aged FDRs of T2DM is unclear. We therefore investigated the association between circulating irisin and pancreatic β-cell function in normal-glucose-tolerance (NGT) subjects.

          Methods

          In this cross-sectional study, we recruited 412 supposed healthy subjects aged 40-60 who were FDRs of T2DM patients but without previous diagnosis of T2DM. Of the 412 individuals, 254 had NGT and 60 were newly diagnosed T2DM based on the results of a 75 g oral glucose tolerance test (OGTT- World Health Organization diagnostic criteria). We measured irisin in the newly diagnosed T2DM group (n = 60) and in an age- and sex-matched NGT subgroups (n = 62). Serum irisin was quantified by ELISA, and its association with metabolic parameters was analysed by Pearson’s correlation and multiple linear regression analyses.

          Results

          There was no significant difference in serum irisin between middle-aged newly diagnosed T2DM patients and the NGT control group. Circulating irisin was correlated with haemoglobin A1c (r = 0.202, p = 0.026) and estimated glomerular filtration rate (r = 0.239, p = 0.010). Multiple linear regression revealed that only homeostasis model assessment-β (HOMA-β) was associated with irisin in NGT subjects after adjusting for confounding factors. However, similar analysis in T2DM did not reveal a significant association between circulating irisin and metabolic parameters.

          Conclusions

          There was no significant difference in serum irisin between middle-aged newly diagnosed T2DM patients and the NGT controls. Serum irisin level was closely related to HOMA-β in NGT, suggesting that irisin may play a crucial role in pancreatic β-cell function.

          Related collections

          Most cited references32

          • Record: found
          • Abstract: found
          • Article: not found

          Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.

          By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance.

            Recently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice. The objective of the study was to investigate FNDC5 gene expression in human muscle and adipose tissue and circulating irisin according to obesity, insulin sensitivity, and type 2 diabetes. Adipose tissue FNDC5 gene expression and circulating irisin (ELISA) were analyzed in 2 different cohorts (n = 125 and n = 76); muscle FNDC5 expression was also evaluated in a subcohort of 34 subjects. In vitro studies in human preadipocytes and adipocytes and in induced browning of 3T3-L1 cells (by means of retinoblastoma 1 silencing) were also performed. In both sc and visceral adipose tissue, FNDC5 gene expression decreased significantly in association with obesity and was positively associated with brown adipose tissue markers, lipogenic, insulin pathway-related, mitochondrial, and alternative macrophage gene markers and negatively associated with LEP, TNFα, and FSP27 (a known repressor of brown genes). Circulating irisin and irisin levels in adipose tissue were significantly associated with FNDC5 gene expression in adipose tissue. In muscle, the FNDC5 gene was 200-fold more expressed than in adipose tissue, and its expression was associated with body mass index, PGC1α, and other mitochondrial genes. In obese participants, FNDC5 gene expression in muscle was significantly decreased in association with type 2 diabetes. Interestingly, muscle FNDC5 gene expression was significantly associated with FNDC5 and UCP1 gene expression in visceral adipose tissue. In men, circulating irisin levels were negatively associated with obesity and insulin resistance. Irisin was secreted from human adipocytes into the media, and the induction of browning in 3T3-L1 cells led to increased secreted irisin levels. Decreased circulating irisin concentration and FNDC5 gene expression in adipose tissue and muscle from obese and type 2 diabetic subjects suggests a loss of brown-like characteristics and a potential target for therapy.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling.

              The number and activity of brown adipocytes are linked to the ability of mammals to resist body fat accumulation. In some conditions, certain white adipose tissue (WAT) depots are readily convertible to a ''brown-like'' state, which is associated with weight loss. Irisin, a newly identified hormone, is secreted by skeletal muscles into circulation and promotes WAT "browning" with unknown mechanisms. In the current study, we demonstrated in mice that recombinant irisin decreased the body weight and improved glucose homeostasis. We further showed that irisin upregulated uncoupling protein-1 (UCP-1; a regulator of thermogenic capability of brown fat) expression. This effect was possibly mediated by irisin-induced phosphorylation of the p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-related kinase (ERK) signaling pathways. Inhibition of the p38 MAPK by SB203580 and ERK by U0126 abolished the upregulatory effect of irisin on UCP-1. In addition, irisin also promoted the expression of betatrophin, another newly identified hormone that promotes pancreatic β-cell proliferation and improves glucose tolerance. In summary, our data suggest that irisin can potentially prevent obesity and associated type 2 diabetes by stimulating expression of WAT browning-specific genes via the p38 MAPK and ERK pathways.
                Bookmark

                Author and article information

                Contributors
                yangmeili51@126.com
                cph502@163.com
                jinhua_98097@126.com
                379601893@qq.com
                254570955@qq.com
                906633172@qq.com
                xuemeiyu2002@hotmail.com
                Journal
                Diabetol Metab Syndr
                Diabetol Metab Syndr
                Diabetology & Metabolic Syndrome
                BioMed Central (London )
                1758-5996
                5 December 2014
                5 December 2014
                2014
                : 6
                : 1
                : 133
                Affiliations
                [ ]Department of endocrinology and Metabolism, Fengxian Central Hospital, Shanghai, China
                [ ]Department of endocrinology and Metabolism, The First Clinical Medical College of Suzhou University, Suzhou, China
                Article
                388
                10.1186/1758-5996-6-133
                4271516
                15b6b71e-846f-4658-aa6a-f8bf0da91a1b
                © Yang et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 February 2014
                : 20 November 2014
                Categories
                Research
                Custom metadata
                © The Author(s) 2014

                Nutrition & Dietetics
                type 2 diabetes mellitus,first-degree relatives,irisin,pancreatic β-cell

                Comments

                Comment on this article