The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.

Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Nature Medicine (Impact Factor: 28.05). 09/2001; 7(8):941-6. DOI: 10.1038/90984
Source: PubMed

ABSTRACT Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.

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    Planta Med 2014, Braga - Portugal; 08/2014
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    ABSTRACT: There are few reports on the effects of ethnicity or gender in the association between adipocytokines and insulin resistance in children of different ages. This study assessed associations between serum concentrations of adiponectin/resistin and parameters of insulin resistance in children from 4 different countries. A total of 2,290 children were analyzed in this study; each was from one of 4 different countries (Japan, Thailand, Italy and USA), and grouped according to age (8-11 years old in Group 1 and 12-15 years old in Group 2). Adioponectin was higher in female than in male children, and in Group 1 than in Group 2. Generally, adiponectin was lower in Asian as compared to Italian and American children. These tendencies remained even after adjustment for body mass index (BMI) or waist circumstance (WC). Among older children (Group 2), resistin was higher in female than in male children. Significant correlations by non-parametric univariate correlation coefficients and Spearman's rank correlation coefficients were found between adiponectin and homeostasis model assessment of insulin resistance (HOMA-IR), and fasting serum insulin levels in young Japanese, Italian, and American female children(p < 0.01, p < 0.05, p < 0.05, respectively). Correlations between serum adiponectin and HOMA-IR were also found among older male Italian, American, and Thai children (p < 0.05, p < 0.001, p < 0.001, respectively). In multiple regression analysis by forced entry method, adiponectin correlated with HOMA-IR in Italian and American male children, and in all older female children regardless of country of origin. There was no correlation between resistin and markers of insulin resistance in children from any of the countries. We conclude that serum adiponectin concentrations are lower in Asian as compared to Italian and American children, and that adiponectin but not resistin contributes to differences in markers for insulin resistance in children from different populations.
    International Journal of Pediatric Endocrinology 01/2015; 2015(1):2. DOI:10.1186/1687-9856-2015-2
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    ABSTRACT: The aim of this dissertation is to evaluate the impact of type 2 diabetes mellitus on oxidative stress and inflammation in the bone marrow and circulation, as well as investigate the relationship between these molecular alterations and long-term complications of diabetes, specifically cardiovascular disease. In addition, the role of the peptide Ang-(1-7) i as well as the receptor and second messager systems involved in reversing these molecular alterations and complications will also be determined. ❧ The research integrates multiple in vivo studies and a clinical study to provide a comprehensive picture of this disease state. Nitrite levels in the bone marrow and blood were measured using the Griess reaction. Expression and protein levels of molecular markers of oxidative stress and cytokines were determined using RT-PCR, western blot, and ELISA. Levels of oxidative stress, protein tyrosine nitration in the bone marrow, intracellular cytokine levels, and EPC counts were measured using flow cytometric methodologies. Tissue protein nitration was measured by immunohistochemistry. Murine heart function was determined in vivo using small animal echocardiography and thermodilution techniques, and histology was used to measure cardiomyocytes in stained heart sections. Culture of isolated bone marrow cells was used to determine various progenitor counts. ❧ Our in vivo and clinical data indicate that oxidative stress and systemic inflammation play a major role in both type 2 diabetes and gestational diabetes. In addition, we illustrate a potential link between these pathologies and endothelial and cardiovascular dysfunction in this disease state. Treatment of db/db mice with Ang-(1-7) for 14 days resulted in decreases in markers of oxidative stress and inflammation, increases in bone marrow-derived and circulating EPC, as well as increases in other bone marrow-derived progenitors involved in vasculogenesis and immune function. Lastly, Ang-(1-7) treatment helped to increase measures of cardiac function that were reduced in diabetic mice. ❧ While a focus on glucose control is still of the utmost importance, more attention needs to be spent on reversing the pre-existing cellular damage caused by oxidative stress and inflammation in diabetes. Ang-(1-7) may be one of multiple promising agents with the ability to work synergistically with currently FDA-approved therapies; together able to reduce plasma glucose levels, preventing further damage, and reverse oxidative stress and inflammation in type 2 diabetes. Combined, this therapeutic strategy could potentially significantly reduce the risk of some of the long-term and deadly complications of diabetes, including cardiovascular disease.
    04/2012, Degree: Ph.D., Supervisor: Stan Louie, Kathleen Rodgers, Wei-Chiang Shen, Gere diZerega, Curtis Okamoto