Dataset Information

Body iron stores and glucose intolerance in premenopausal women: role of hyperandrogenism, insulin resistance, and genomic variants related to inflammation, oxidative stress, and iron metabolism.

ABSTRACT: OBJECTIVE Increased serum ferritin levels and iron stores may be involved in the development of abnormal glucose tolerance in women presenting with obesity and/or polycystic ovary syndrome (PCOS). We aimed to study the determinants of serum ferritin levels in premenopausal women among indexes of insulin resistance, adiposity, hyperandrogenism, and genotypes pertaining to inflammation, oxidative stress, and iron metabolism. RESEARCH DESIGN AND METHODS A total of 257 premenopausal women, classified depending on the presence or absence of PCOS, obesity, and/or abnormal glucose tolerance, underwent a complete metabolic evaluation, serum ferritin, haptoglobin, and C-reactive protein (CRP) measurements, and genotyping for proinflammatory and prooxidant variants and mutations in the HFE gene. RESULTS Serum ferritin concentrations were increased in women presenting with PCOS and/or abnormal glucose tolerance, independent of obesity. A stepwise multivariate linear regression analysis (R(2) = 0.18, P < 0.0001) retained menstrual dysfunction (beta = 0.14, P = 0.035), free testosterone (beta = 0.14, P = 0.052), insulin sensitivity index (beta = -0.12, P = 0.012), the His63Asp variant in HFE (beta = 0.16, P = 0.008), and abnormal glucose tolerance (beta = 0.15, P = 0.015) as significant predictors of the logarithm of ferritin levels, whereas CRP, haptoglobin, waist-to-hip ratio, or variants in the TNFalpha, TNFRSF1B, IL6, IL6ST, IL6Ralpha, PON1, and HFE Cys282Tyr mutation exerted no influence. CONCLUSIONS Androgen excess (partly because of hyperandrogenemia and partly because of menstrual dysfunction), insulin resistance, abnormal glucose tolerance, and the HFE His63Asp variant correlate with ferritin levels in premenopausal women.

SUBMITTER: Martinez-Garcia MA

PROVIDER: S-EPMC2713652 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Body iron stores and glucose intolerance in premenopausal women: role of hyperandrogenism, insulin resistance, and genomic variants related to inflammation, oxidative stress, and iron metabolism.

Martínez-García M Angeles MA Luque-Ramírez Manuel M San-Millán José L JL Escobar-Morreale Héctor F HF

Diabetes care 20090428 8

OBJECTIVE Increased serum ferritin levels and iron stores may be involved in the development of abnormal glucose tolerance in women presenting with obesity and/or polycystic ovary syndrome (PCOS). We aimed to study the determinants of serum ferritin levels in premenopausal women among indexes of insulin resistance, adiposity, hyperandrogenism, and genotypes pertaining to inflammation, oxidative stress, and iron metabolism. RESEARCH DESIGN AND METHODS A total of 257 premenopausal women, classifie ...[more]

PMID: 19401444

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Project description:The pro-inflammatory cytokine, Interleukin-6 (IL-6), has been proposed to be one of the mediators that link chronic inflammation to glucose intolerance and insulin resistance. Many studies have demonstrated the effects of IL-6 on insulin action in the skeletal muscle. However, few studies have investigated the effect of long-term treatment of IL-6, leading to glucose intolerance and insulin resistance. In the present study, we observed protective effects of alantolactone, a sesquiterpene lactone isolated from Inula helenium against glucose intolerance and insulin resistance induced by prolonged exposure of IL-6. Alantolactone has been reported to have anti-inflammatory and anti-cancer effects through IL-6-induced signal transducer and activator of transcription 3 (STAT3) signaling pathway. The relationship between IL-6 exposure and expression of toll-like receptor 4 (TLR4), involved in inflammation in the skeletal muscle, and the underlying mechanisms were investigated. We observed maximum dysregulation of glucose uptake after 40 ng/ml IL-6 induction for 24 h in L6 myotubes. Prolonged IL-6 exposure suppressed glucose uptake regulating alpha serine/threonine-protein kinase (AKT) phosphorylation; however, pretreatment with alantolactone activated AKT phosphorylation and improved glucose uptake. Alantolactone also attenuated IL-6-stimulated STAT3 phosphorylation, followed by an increase in expression of negative regulator suppressor of cytokine signaling 3 (SOCS3). Furthermore, IL-6-induced expression of pathogen recognition receptor, TLR4, was also suppressed by alantolactone pretreatment. Post-silencing of STAT3 using siRNA approach, IL-6-stimulated siRNA-STAT3 improved glucose uptake and suppressed TLR4 gene expression. Taken together, we propose that, as a STAT3 inhibitor, alantolactone, improves glucose regulation in the skeletal muscle by inhibiting IL-6-induced STAT3-SOCS3 signaling followed by inhibition of the TLR4 gene expression. Therefore, alantolactone can be a promising candidate for the treatment of inflammation-associated glucose intolerance and insulin resistance.

Dataset Information

Body iron stores and glucose intolerance in premenopausal women: role of hyperandrogenism, insulin resistance, and genomic variants related to inflammation, oxidative stress, and iron metabolism.

Publications

Body iron stores and glucose intolerance in premenopausal women: role of hyperandrogenism, insulin resistance, and genomic variants related to inflammation, oxidative stress, and iron metabolism.

Similar Datasets

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