TY - JOUR A1 - Manowsky, Julia A1 - Camargo, Rodolfo Gonzalez A1 - Kipp, Anna Patricia A1 - Henkel, Janin A1 - Püschel, Gerhard Paul T1 - Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes JF - American journal of physiology : Endocrinology and metabolism N2 - Overweight and obesity are associated with hyperinsulinemia, insulin resistance, and a low-grade inflammation. Although hyperinsulinemia is generally thought to result from an attempt of the beta-cell to compensate for insulin resistance, there is evidence that hyperinsulinaemia itself may contribute to the development of insulin resistance and possibly the low-grade inflammation. To test this hypothesis, U937 macrophages were exposed to insulin. In these cells, insulin induced expression of the proinflammatory cytokines IL-1 beta, IL-8, CCL2, and OSM. The insulin-elicited induction of IL-1 beta was independent of the presence of endotoxin and most likely mediated by an insulin-dependent activation of NF-kappa B. Supernatants of the insulin-treated U937 macrophages rendered primary cultures of rat hepatocytes insulin resistant; they attenuated the insulin-dependent induction of glucokinase by 50%. The cytokines contained in the supernatants of insulin-treated U937 macrophages activated ERK1/2 and IKK beta, resulting in an inhibitory serine phosphorylation of the insulin receptor substrate. In addition, STAT3 was activated and SOCS3 induced, further contributing to the interruption of the insulin receptor signal chain in hepatocytes. These results indicate that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues. KW - metabolic syndrome KW - type 2 diabetes KW - inflammation KW - macrophage KW - insulin KW - cytokines Y1 - 2016 U6 - https://doi.org/10.1152/ajpendo.00427.2015 SN - 0193-1849 SN - 1522-1555 VL - 310 SP - E938 EP - E946 PB - American Chemical Society CY - Bethesda ER - TY - JOUR A1 - Karuwanarint, Piyaporn A1 - Phonrat, Benjaluck A1 - Tungtrongchitr, Anchalee A1 - Suriyaprom, Kanjana A1 - Chuengsamarn, Somlak A1 - Schweigert, Florian J. A1 - Tungtrongchitr, Rungsunn T1 - Vitamin D-binding protein and its polymorphisms as a predictor for metabolic syndrome JF - Biomarkers in medicine N2 - Aim: To investigate the relationship of vitamin D-binding protein (GC) and genetic variation of GC (rs4588, rs7041 and rs2282679) with metabolic syndrome (MetS) in the Thai population. Materials & methods: GCglobulin concentrations were measured by quantitative western blot analysis in 401 adults. All participants were genotyped using TaqMan allelic discrimination assays. Results: GC-globulin levels were significatly lower in MetS subjects than in control subjects, in which significant negative correlations of GC-globulin levels with systolic blood pressure, glucose and age were found. Male participants who carried the GT genotype for rs4588 showed an increased risk of MetS compared with the GG wild-type (odds ratio: 3.25; p = 0.004). Conclusion: GC-globulin concentrations and variation in GC rs4588 were supported as a risk factor for MetS in Thais. KW - GC gene KW - GC-globulin KW - metabolic syndrome KW - polymorphism KW - Thai population KW - vitamin D-binding protein Y1 - 2018 U6 - https://doi.org/10.2217/bmm-2018-0029 SN - 1752-0363 SN - 1752-0371 VL - 12 IS - 5 SP - 465 EP - 473 PB - Future Medicine CY - London ER - TY - JOUR A1 - Osei, Francis A1 - Block, Andrea A1 - Wippert, Pia-Maria T1 - Association of primary allostatic load mediators and metabolic syndrome (MetS): A systematic review JF - Frontiers in Endocrinology N2 - Allostatic load (AL) exposure may cause detrimental effects on the neuroendocrine system, leading to metabolic syndrome (MetS). The primary mediators of AL involve serum dehydroepiandrosterone sulfate (DHEAS; a functional HPA axis antagonist); further, cortisol, urinary norepinephrine (NE), and epinephrine (EPI) excretion levels (assessed within 12-h urine as a golden standard for the evaluation of the HPA axis activity and sympathetic nervous system activity). However, the evidence of an association between the primary mediators of AL and MetS is limited. This systematic review aimed to critically examine the association between the primary mediators of AL and MetS. PubMed and Web of Science were searched for articles from January 2010 to December 2021, published in English. The search strategy focused on cross-sectional and case–control studies comprising adult participants with MetS, obesity, overweight, and without chronic diseases. The STROBE checklist was used to assess study quality control. Of 770 studies, twenty-one studies with a total sample size (n = 10,666) met the eligibility criteria. Eighteen studies were cross-sectional, and three were case–control studies. The included studies had a completeness of reporting score of COR % = 87.0 ± 6.4%. It is to be noted, that cortisol as a primary mediator of AL showed an association with MetS in 50% (urinary cortisol), 40% (serum cortisol), 60% (salivary cortisol), and 100% (hair cortisol) of the studies. For DHEAS, it is to conclude that 60% of the studies showed an association with MetS. In contrast, urinary EPI and urinary NE had 100% no association with MetS. In summary, there is a tendency for the association between higher serum cortisol, salivary cortisol, urinary cortisol, hair cortisol, and lower levels of DHEAS with MetS. Future studies focusing on longitudinal data are warranted for clarification and understanding of the association between the primary mediators of AL and MetS. KW - allostatic load KW - cortisol KW - dehydroepiandrosterone sulfate KW - epinephrine KW - norepinephrine KW - metabolic syndrome KW - primary marker Y1 - 2022 U6 - https://doi.org/10.3389/fendo.2022.946740 SN - 1664-2392 VL - 13 PB - Frontiers CY - Lausanne, Schweiz ER -