@article{KesslerHornemannRudovichetal.2020,
  author    = {Kessler, Katharina and Hornemann, Silke and Rudovich, Natalia and Weber, Daniela and Grune, Tilman and Kramer, Achim and Pfeiffer, Andreas F. H. and Pivovarova-Ramich, Olga},
  title     = {Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers},
  series = {Nutrients},
  journal   = {Nutrients},
  number    = {2},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2072-6643},
  doi       = {10.3390/nu12020340},
  pages     = {1 -- 12},
  year      = {2020},
  abstract  = {Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies.},
  language  = {en}
}
@article{HenkelKlauderStatzetal.2021,
  author    = {Henkel, Janin and Klauder, Julia and Statz, Meike and Wohlenberg, Anne-Sophie and Kuipers, Sonja and Vahrenbrink, Madita and P{\"u}schel, Gerhard Paul},
  title     = {Enhanced Palmitate-Induced Interleukin-8 Formation in Human Macrophages by Insulin or Prostaglandin E-2},
  series = {Biomedicines},
  volume    = {9},
  journal   = {Biomedicines},
  number    = {5},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines9050449},
  pages     = {10},
  year      = {2021},
  abstract  = {Macrophages in pathologically expanded dysfunctional white adipose tissue are exposed to a mix of potential modulators of inflammatory response, including fatty acids released from insulin-resistant adipocytes, increased levels of insulin produced to compensate insulin resistance, and prostaglandin E-2 (PGE(2)) released from activated macrophages. The current study addressed the question of how palmitate might interact with insulin or PGE(2) to induce the formation of the chemotactic pro-inflammatory cytokine interleukin-8 (IL-8). Human THP-1 cells were differentiated into macrophages. In these macrophages, palmitate induced IL-8 formation. Insulin enhanced the induction of IL-8 formation by palmitate as well as the palmitate-dependent stimulation of PGE(2) synthesis. PGE(2) in turn elicited IL-8 formation on its own and enhanced the induction of IL-8 release by palmitate, most likely by activating the EP4 receptor. Since IL-8 causes insulin resistance and fosters inflammation, the increase in palmitate-induced IL-8 formation that is caused by hyperinsulinemia and locally produced PGE(2) in chronically inflamed adipose tissue might favor disease progression in a vicious feed-forward cycle.},
  language  = {en}
}
@article{AgaBarfknechtHallahanGottmannetal.2020,
  author    = {Aga-Barfknecht, Heja and Hallahan, Nicole and Gottmann, Pascal and J{\"a}hnert, Markus and Osburg, Sophie and Schulze, Gunnar and Kamitz, Anne and Arends, Danny and Brockmann, Gudrun and Schallschmidt, Tanja and Lebek, Sandra and Chadt, Alexandra and Al-Hasani, Hadi and Joost, Hans-Georg and Sch{\"u}rmann, Annette and Vogel, Heike},
  title     = {Identification of novel potential type 2 diabetes genes mediating beta-cell loss and hyperglycemia using positional cloning},
  series = {Frontiers in genetics},
  volume    = {11},
  journal   = {Frontiers in genetics},
  publisher = {Frontiers Media},
  address   = {Lausanne},
  issn      = {1664-8021},
  doi       = {10.3389/fgene.2020.567191},
  pages     = {11},
  year      = {2020},
  abstract  = {Type 2 diabetes (T2D) is a complex metabolic disease regulated by an interaction of genetic predisposition and environmental factors. To understand the genetic contribution in the development of diabetes, mice varying in their disease susceptibility were crossed with the obese and diabetes-prone New Zealand obese (NZO) mouse. Subsequent whole-genome sequence scans revealed one major quantitative trait loci (QTL),Nidd/DBAon chromosome 4, linked to elevated blood glucose and reduced plasma insulin and low levels of pancreatic insulin. Phenotypical characterization of congenic mice carrying 13.6 Mbp of the critical fragment of DBA mice displayed severe hyperglycemia and impaired glucose clearance at week 10, decreased glucose response in week 13, and loss of beta-cells and pancreatic insulin in week 16. To identify the responsible gene variant(s), further congenic mice were generated and phenotyped, which resulted in a fragment of 3.3 Mbp that was sufficient to induce hyperglycemia. By combining transcriptome analysis and haplotype mapping, the number of putative responsible variant(s) was narrowed from initial 284 to 18 genes, including gene models and non-coding RNAs. Consideration of haplotype blocks reduced the number of candidate genes to four (Kti12,Osbpl9,Ttc39a, andCalr4) as potential T2D candidates as they display a differential expression in pancreatic islets and/or sequence variation. In conclusion, the integration of comparative analysis of multiple inbred populations such as haplotype mapping, transcriptomics, and sequence data substantially improved the mapping resolution of the diabetes QTLNidd/DBA. Future studies are necessary to understand the exact role of the different candidates in beta-cell function and their contribution in maintaining glycemic control.},
  language  = {en}
}
@article{HauffeRathAgyapongetal.2022,
  author    = {Hauffe, Robert and Rath, Michaela and Agyapong, Wilson and Jonas, Wenke and Vogel, Heike and Schulz, Tim Julius and Schwarz, Maria and Kipp, Anna Patricia and Bl{\"u}her, Matthias and Kleinridders, Andr{\´e}},
  title     = {Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling},
  series = {Antioxidants},
  volume    = {11},
  journal   = {Antioxidants},
  edition   = {5},
  publisher = {MDPI},
  address   = {Basel, Schweiz},
  issn      = {2076-3921},
  doi       = {10.3390/antiox11050862},
  pages     = {1 -- 16},
  year      = {2022},
  abstract  = {The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.},
  language  = {en}
}
@article{HenkelOberlaenderKlauderStatzetal.2021,
  author    = {Henkel-Oberl{\"a}nder, Janin and Klauder, Julia and Statz, Meike and Wohlenberg, Anne-Sophie and Kuipers, Sonja and Vahrenbrink, Madita and P{\"u}schel, Gerhard},
  title     = {Enhanced Palmitate-Induced Interleukin-8 Formation in Human Macrophages by Insulin or Prostaglandin E₂},
  series = {Biomedicines : open access journal},
  volume    = {9},
  journal   = {Biomedicines : open access journal},
  number    = {5},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines9050449},
  pages     = {10},
  year      = {2021},
  abstract  = {Macrophages in pathologically expanded dysfunctional white adipose tissue are exposed to a mix of potential modulators of inflammatory response, including fatty acids released from insulin-resistant adipocytes, increased levels of insulin produced to compensate insulin resistance, and prostaglandin E₂ (PGE₂) released from activated macrophages. The current study addressed the question of how palmitate might interact with insulin or PGE₂ to induce the formation of the chemotactic pro-inflammatory cytokine interleukin-8 (IL-8). Human THP-1 cells were differentiated into macrophages. In these macrophages, palmitate induced IL-8 formation. Insulin enhanced the induction of IL-8 formation by palmitate as well as the palmitate-dependent stimulation of PGE₂ synthesis. PGE₂ in turn elicited IL-8 formation on its own and enhanced the induction of IL-8 release by palmitate, most likely by activating the EP4 receptor. Since IL-8 causes insulin resistance and fosters inflammation, the increase in palmitate-induced IL-8 formation that is caused by hyperinsulinemia and locally produced PGE₂ in chronically inflamed adipose tissue might favor disease progression in a vicious feed-forward cycle.},
  language  = {en}
}
@article{MoehligFloeterSprangeretal.2006,
  author    = {Moehlig, M. and Floeter, A. and Spranger, Joachim and Weickert, Martin O. and Schill, T. and Schloesser, H. W. and Brabant, G. and Pfeiffer, Andreas F. H. and Selbig, Joachim and Schoefl, C.},
  title     = {Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling},
  series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  volume    = {49},
  journal   = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  publisher = {Springer},
  address   = {Berlin},
  issn      = {0012-186X},
  doi       = {10.1007/s00125-006-0395-0},
  pages     = {2572 -- 2579},
  year      = {2006},
  abstract  = {Aims/hypothesis Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. Materials and methods Consecutive PCOS patients (n=118) with fasting glucose < 6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value >= 7.8 mmol/l) from those with NGT. Results According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone:follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100\% sensitivity, 74\% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100\% sensitivity, 57\% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100\% sensitivity, 29\% specificity to detect IGM). The validity of both trees was tested by a leave-10\%-out cross-validation. Conclusions/interpretation Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced.},
  language  = {en}
}
@article{ManowskyCamargoKippetal.2016,
  author    = {Manowsky, Julia and Camargo, Rodolfo Gonzalez and Kipp, Anna Patricia and Henkel, Janin and P{\"u}schel, Gerhard Paul},
  title     = {Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes},
  series = {American journal of physiology : Endocrinology and metabolism},
  volume    = {310},
  journal   = {American journal of physiology : Endocrinology and metabolism},
  publisher = {American Chemical Society},
  address   = {Bethesda},
  issn      = {0193-1849},
  doi       = {10.1152/ajpendo.00427.2015},
  pages     = {E938 -- E946},
  year      = {2016},
  abstract  = {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.},
  language  = {en}
}
@article{FruscalzoLonderoDriuletal.2015,
  author    = {Fruscalzo, Arrigo and Londero, Ambrogio P. and Driul, Lorenza and Henze, Andrea and Tonutti, Laura and Ceraudo, Maria and Zanotti, Giuseppe and Berni, Rodolfo and Schweigert, Florian J. and Raila, Jens},
  title     = {First trimester concentrations of the TTR-RBP4-retinol complex components as early markers of insulin-treated gestational diabetes mellitus},
  series = {Clinical chemistry and laboratory medicine : journal of the Forum of the European Societies of Clinical Chemistry - the European Branch of the International Federation of Clinical Chemistry and Laboratory Medicine},
  volume    = {53},
  journal   = {Clinical chemistry and laboratory medicine : journal of the Forum of the European Societies of Clinical Chemistry - the European Branch of the International Federation of Clinical Chemistry and Laboratory Medicine},
  number    = {10},
  publisher = {De Gruyter},
  address   = {Berlin},
  issn      = {1434-6621},
  doi       = {10.1515/cclm-2014-0929},
  pages     = {1643 -- 1651},
  year      = {2015},
  abstract  = {Background: The objective of the study was to investigate the relationship between first trimester maternal serum levels of the TTR-RBP4-ROH complex components and the later insurgence of an altered glucose metabolism during pregnancy. Methods: Retrospective case control study including 96 patients between the 12th and 14th week of gestation, 32 that developed gestational diabetes mellitus (GDM), respectively, 21 non-insulin-treated (dGDM) and 11 insulin-treated (iGDM), 20 large for gestational age fetuses (LGA) without GDM and 44 patients with normal outcome as control. Serum concentrations of RBP4 and TTR were assessed by ELISA; serum concentration of ROH by reverse-phase high performance liquid chromatography (rpHPLC). The molecular heterogeneity of TTR and RBP4 was analyzed after immunoprecipitation by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Results: iGDM patients were characterized by reduced TTR, RBP4 and ROH compared to controls (respectively, iGDM vs. controls, mean +/- SD: TTR 3.96 +/- 0.89 mu mol/L vs. 4.68 +/- 1.21 mu mol/L, RBP4 1.13 +/- 0.25 mu mol/L vs. 1.33 +/- 0.38 mu mol/L and ROH 1.33 +/- 0.17 mu mol/L vs. 1.62 +/- 0.29 mu mol/L, p < 0.05). TTR containing Gly10 in place of Cys10 was lower in the iGDM group (p < 0.05) compared to controls. In the final logistic regression model ROH significantly predicted the diagnosis of iGDM (OR 0.93, 95\% CI 0.87-0.98, p < 0.05). Conclusions: First trimester maternal serum ROH, RBP4 and TTR represent potential biomarkers associated with the development of iGDM.},
  language  = {en}
}