TY - JOUR A1 - Hauffe, Robert A1 - Rath, Michaela A1 - Agyapong, Wilson A1 - Jonas, Wenke A1 - Vogel, Heike A1 - Schulz, Tim Julius A1 - Schwarz, Maria A1 - Kipp, Anna Patricia A1 - Blüher, Matthias A1 - Kleinridders, André T1 - Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling JF - Antioxidants N2 - 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. KW - selenite KW - insulin KW - adipose tissue KW - obesity KW - insulin resistance Y1 - 2022 U6 - https://doi.org/10.3390/antiox11050862 SN - 2076-3921 VL - 11 SP - 1 EP - 16 PB - MDPI CY - Basel, Schweiz ET - 5 ER - TY - JOUR A1 - Fedders, Ronja A1 - Muenzner, Matthias A1 - Weber, Pamela A1 - Sommerfeld, Manuela A1 - Knauer, Miriam A1 - Kedziora, Sarah A1 - Kast, Naomi A1 - Heidenreich, Steffi A1 - Raila, Jens A1 - Weger, Stefan A1 - Henze, Andrea A1 - Schupp, Michael T1 - Liver-secreted RBP4 does not impair glucose homeostasis in mice JF - The journal of biological chemistry N2 - Retinol-binding protein 4 (RBP4) is the major transport protein for retinol in blood. Recent evidence from genetic mouse models shows that circulating RBP4 derives exclusively from hepatocytes. Because RBP4 is elevated in obesity and associates with the development of glucose intolerance and insulin resistance, we tested whether a liver-specific overexpression of RBP4 in mice impairs glucose homeostasis. We used adeno-associated viruses (AAV) that contain a highly liver-specific promoter to drive expression of murine RBP4 in livers of adult mice. The resulting increase in serum RBP4 levels in these mice was comparable with elevated levels that were reported in obesity. Surprisingly, we found that increasing circulating RBP4 had no effect on glucose homeostasis. Also during a high-fat diet challenge, elevated levels of RBP4 in the circulation failed to aggravate the worsening of systemic parameters of glucose and energy homeostasis. These findings show that liver-secreted RBP4 does not impair glucose homeostasis. We conclude that a modest increase of its circulating levels in mice, as observed in the obese, insulin-resistant state, is unlikely to be a causative factor for impaired glucose homeostasis. KW - liver KW - retinoid-binding protein KW - glucose metabolism KW - insulin resistance KW - mouse KW - TTR Y1 - 2018 U6 - https://doi.org/10.1074/jbc.RA118.004294 SN - 1083-351X VL - 293 IS - 39 SP - 15269 EP - 15276 PB - American Society for Biochemistry and Molecular Biology CY - Bethesda ER - TY - JOUR A1 - Moehlig, M. A1 - Floeter, A. A1 - Spranger, Joachim A1 - Weickert, Martin O. A1 - Schill, T. A1 - Schloesser, H. W. A1 - Brabant, G. A1 - Pfeiffer, Andreas F. H. A1 - Selbig, Joachim A1 - Schoefl, C. T1 - Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling JF - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) N2 - 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. KW - decision tree KW - HOMA KW - impaired glucose tolerance KW - insulin KW - insulin resistance KW - polycystic ovary syndrome KW - proinsulin KW - type 2 diabetes mellitus Y1 - 2006 U6 - https://doi.org/10.1007/s00125-006-0395-0 SN - 0012-186X VL - 49 SP - 2572 EP - 2579 PB - Springer CY - Berlin ER - TY - JOUR A1 - Hocher, Berthold A1 - Heimerl, Dirk A1 - Slowinski, Torsten A1 - Godes, Michael A1 - Halle, Horst A1 - Priem, Friedrich A1 - Pfab, Thiemo T1 - Birthweight and Fetal Glycosylated Hemoglobin at Birth in Newborns Carrying the GLUT1 XbaI Gene Polymorphism JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: Low birthweight is an independent risk factor of glucose intolerance and type 2 diabetes in later life. Genetically determined insulin resistance and subsequently impaired glucose uptake might explain both reduced fetal growth and elevated blood glucose. The glucose transporter 1 (GLUT!) plays an important role for fetal glucose uptake as well as for maternal-fetal glucose transfer, and it has been associated with insulin resistance in adults. The present study hypothesized that the common fetal GLUT1 XbaI polymorphism might reduce fetal insulin sensitivity and/or glucose supply in utero, thus affecting fetal blood glucose and fetal growth. Methods: A genetic association study was conducted at the obstetrics department of the Charite University Hospital, Berlin, Germany. 119.1 white women were included after delivery, and all newborns were genotyped for the GLUT1 XbaI polymorphism. Total glycosylated hemoglobin was quantified, serving as a surrogate of glycemia during the last weeks of pregnancy. Results: The analysis of this large population showed no significant differences in fetal glycosylated hemoglobin or birthweight for the different fetal GLUT1 XbaI genotypes. Only newborns carrying the mutated allele show the previously published inverse association between birthweight and glycosylated hemoglobin. Conclusions: The results suggest that there is no prenatal effect of the fetal GLUT1 XbaI polymorphism on fetal insulin sensitivity, intrauterine fetal glucose supply or fetal growth. However, the polymorphism seems to modulate the inverse interaction between birthweight and fetal glycemia. KW - GLUT1 XbaI gene polymorphism KW - birthweight KW - total glycosylated hemoglobin KW - insulin resistance KW - fetal programming Y1 - 2011 SN - 1433-6510 VL - 57 IS - 9-10 SP - 651 EP - 657 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Li, Jian A1 - Wang, Zi-Neng A1 - Schlemm, Ludwig A1 - Pfab, Thiemo A1 - Xiao, Xiao-Min A1 - Chen, You-Peng A1 - Hocher, Berthold T1 - Low birth weight and elevated head-to-abdominal circumference ratio are associated with elevated fetal glycated serum protein concentrations JF - Journal of hypertension N2 - Objective To analyze the association between low birth weight, head-to-abdominal circumference ratio, and insulin resistance in early life. Method and results Glycated serum proteins (GSPs) were quantified at delivery in 612 Chinese mother/child pairs serving as a surrogate of maternal and fetal glycemia. Differential ultrasound examination of the fetal's body (head circumference, biparietal diameter, pectoral diameter, abdominal circumference, and femur length) was done in average 1 week prior to delivery. Multivariable regression analysis considering gestational age at delivery, the child's sex, maternal BMI, maternal age at delivery, maternal body weight, and pregnancyinduced hypertension revealed that fetal GSP was inversely associated with birth weight (R(2) = 0.416; P < 0.001). Fetal GSP was furthermore positively associated with the head-to-abdominal circumference ratio, whereas the maternal GSP was negatively correlated with the offspring's head-to-abdominal circumference ratio (R(2) = 0.285; P = 0.010 and R(2) = 0.261; P = 0.020, respectively). The increased head-to-abdominal circumference ratio in newborns with higher fetal GSP is mainly due to a reduced abdominal circumference rather than reduced growth of the brain. Conclusion The disproportional intrauterine growth is in line with the concept of so-called brain sparing, a mechanism maintaining the intrauterine growth of the brain at the expense of trunk growth. Our data suggest that the low birth weight phenotype, linked to cardiovascular diseases like hypertension in later life, might be a phenotype of disproportional intrauterine growth retardation and early life insulin resistance. KW - disproportional intrauterine growth retardation KW - insulin resistance KW - low birth weight KW - ultrasound Y1 - 2011 U6 - https://doi.org/10.1097/HJH.0b013e328349a2e6 SN - 0263-6352 VL - 29 IS - 9 SP - 1712 EP - 1718 PB - Lippincott Williams & Wilkins CY - Philadelphia ER -