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Showing papers by "Andreas Pfeiffer published in 2008"


Journal ArticleDOI
05 Dec 2008-Science
TL;DR: The technique relies on establishing an absolute reference point in the laboratory frame by elliptical polarization of the laser pulse, from which field-induced momentum shifts of the emergent electron can be assigned to a temporal delay on the basis of the known oscillation of the field vector.
Abstract: It is well established that electrons can escape from atoms through tunneling under the influence of strong laser fields, but the timing of the process has been controversial and far too rapid to probe in detail. We used attosecond angular streaking to place an upper limit of 34 attoseconds and an intensity-averaged upper limit of 12 attoseconds on the tunneling delay time in strong field ionization of a helium atom. The ionization field derives from 5.5-femtosecond-long near-infrared laser pulses with peak intensities ranging from 2.3 × 1014 to 3.5 × 1014 watts per square centimeter (corresponding to a Keldysh parameter variation from 1.45 to 1.17, associated with the onset of efficient tunneling). The technique relies on establishing an absolute reference point in the laboratory frame by elliptical polarization of the laser pulse, from which field-induced momentum shifts of the emergent electron can be assigned to a temporal delay on the basis of the known oscillation of the field vector.

644 citations


Journal ArticleDOI
TL;DR: DF consumption contributes to a number of unexpected metabolic effects independent from changes in body weight, which include improvement of insulin sensitivity, modulation of the secretion of certain gut hormones, and effects on various metabolic and inflammatory markers that are associated with the metabolic syndrome.
Abstract: A high dietary fiber (DF) intake is emphasized in the recommendations of most diabetes and nutritional associations. It is accepted that viscous and gel-forming properties of soluble DF inhibit macronutrient absorption, reduce postprandial glucose response, and beneficially influence certain blood lipids. Colonic fermentation of naturally available high fiber foods can also be mainly attributed to soluble DF, whereas no difference between soluble and insoluble DF consumption on the regulation of body weight has been observed. However, in prospective cohort studies, it is primarily insoluble cereal DF and whole grains, and not soluble DF, that is consistently associated with reduced diabetes risk, suggesting that further, unknown mechanisms are likely to be involved. Recent research indicates that DF consumption contributes to a number of unexpected metabolic effects independent from changes in body weight, which include improvement of insulin sensitivity, modulation of the secretion of certain gut hormones, and effects on various metabolic and inflammatory markers that are associated with the metabolic syndrome. In this review, we briefly summarize novel findings from recent interventions and prospective cohort studies. We discuss concepts and potential mechanisms that might contribute to the further understanding of the involved processes.

612 citations



Journal ArticleDOI
TL;DR: Postglucose GH-nadir values are assay, gender, age, and BMI specific, indicating the need of individual cutoff limits for each assay.
Abstract: Context: Besides the measurement of IGF-I, GH suppression during an oral glucose tolerance test is recommended to assess the biochemical status in acromegaly. However, the development of highly sensitive and specific GH assays necessitates a critical reevaluation of criteria for diagnosis and follow-up of disease activity. Objective: Our objective was to evaluate the between-method discrepancies in GH determinations by different immunoassays considering further confounders like age, gender, and body mass index (BMI). Design, Subjects, and Methods: We measured GH during a 75-g oral glucose tolerance test in 46 acromegaly patients (18 controlled, 28 uncontrolled; 19 men; 31–63 yr; BMI 26.4 ± 0.4 kg/m2) and 213 healthy subjects (66 men; 20–76 yr; BMI 30 ± 0.5 kg/m2), using three different commercially available assays [Immulite (Diagnostic Products Corp., Los Angeles, CA), Nichols (Nichols Institute Diagnostika GmbH, Bad Vilbel, Germany), and Diagnostic Systems Laboratories (Sinsheim, Germany)] that were cal...

139 citations


Journal ArticleDOI
01 Dec 2008-Diabetes
TL;DR: Existing human data showing elevated RBP4 levels in type 2 diabetic patients may be the result of moderate renal insufficiency rather than support for the suggestion thatRBP4 links obesity to type 2 diabetes.
Abstract: OBJECTIVE— It has been suggested that retinol-binding protein 4 (RBP4) links adiposity, insulin resistance, and type 2 diabetes. However, circulating RBP4 levels are also affected by kidney function. Therefore, the aim of this study was to test whether RBP4 serum levels are primarily associated with kidney function or type 2 diabetes. RESEARCH DESIGN AND METHODS— RBP4 serum concentration was determined by enzyme-linked immunosorbent assay in 126 nondiabetic and 104 type 2 diabetic subjects. The study population was divided according to estimated glomerular filtration rate (eGFR) into the following groups: eGFR >90 ml/min per 1.73 m2 (n = 53), 60–90 ml/min per 1.73 m2 (n = 90), 30–60 ml/min per 1.73 m2 (n = 38), and <30 ml/min per 1.73 m2 (n = 49). Each group was subdivided into nondiabetic and type 2 diabetic subjects. RESULTS— RBP4 serum concentration was elevated (2.65 vs. 2.01 μmol/l; P < 0.001) and eGFR was reduced (56 vs. 74 ml/min per 1.73 m2; P < 0.001) in type 2 diabetic vs. nondiabetic subjects, respectively. By stratifying for eGFR, no more differences in RBP4 serum concentration were detectable between type 2 diabetic and nondiabetic subjects. A linear regression analysis revealed an influence of eGFR (r = −0.477; P < 0.001) but not A1C (r = 0.093; P = 0.185) on RBP4 serum concentration. CONCLUSIONS— Existing human data showing elevated RBP4 levels in type 2 diabetic patients may be the result of moderate renal insufficiency rather than support for the suggestion that RBP4 links obesity to type 2 diabetes.

105 citations



Journal ArticleDOI
TL;DR: The occurrence of RBP4 isoforms is not influenced by liver function but seems to be strongly related to kidneys function and may therefore be important in investigating kidney function and related disorders.
Abstract: The levels of retinol-binding protein 4 (RBP4) – the carrier protein for Vitamin A in plasma – are tightly regulated under healthy circumstances. The kidney, the main site of RBP4 catabolism, contributes to an elevation of RBP4 levels during chronic kidney disease (CKD) whereas during chronic liver disease (CLD) RBP4 levels decrease. Little is known about RBP4 isoforms including apo-RBP4, holo-RBP4 as well as RBP4 truncated at the C-terminus (RBP4-L and RBP4-LL) except that RBP4 isoforms have been reported to be increased in hemodialysis patients. Since it is not known whether CLD influence RBP4 isoforms, we investigated RBP4 levels, apo- and holo-RBP4 as well as RBP4-L and RBP4-LL in plasma of 36 patients suffering from CKD, in 55 CLD patients and in 50 control subjects. RBP4 was determined by ELISA and apo- and holo-RBP4 by native polyacrylamide gel electrophoresis (PAGE). RBP4-L and RBP4-LL were analyzed after immunoprecipitation by mass spectrometry (MALDI-TOF-MS). RBP4 isoforms and levels were highly increased in CKD patients compared to controls (P < 0.05) whereas in CLD patients RBP4 isoforms were not different from controls. In addition, in hepatic dysfunction RBP4 levels were decreased whereas the amount of isoforms was not affected. The occurrence of RBP4 isoforms is not influenced by liver function but seems to be strongly related to kidney function and may therefore be important in investigating kidney function and related disorders.

81 citations


Journal ArticleDOI
TL;DR: GIP receptors interact with estrogens in the hypothalamic regulation of food intake in mice, and their blockade may carry promising potential for the prevention of obesity in gonadal steroid deficiency.
Abstract: Menopause and premature gonadal steroid deficiency are associated with increases in fat mass and body weight. Ovariectomized (OVX) mice also show reduced locomotor activity. Glucose-dependent-insul...

52 citations


Journal ArticleDOI
TL;DR: The mechanism of iv lipid and heparin infusion-induced elevation of circulating androgens described here might contribute to the development of hyperandrogenism in women with PCOS and suggests that lowering of hyperlipidemia might be a potential therapeutic target in patients with PCos to treat hyperandrogensemia.
Abstract: Background: The polycystic ovarian syndrome (PCOS) is characterized by hyperandrogenism and associated with obesity and impaired glucose metabolism. Despite the high prevalence of PCOS and the considerable clinical impact, the precise interplay between metabolism and hyperandrogenemia is not entirely clear. Objective: The objective of the study was to analyze the effects of iv lipid and heparin infusion on circulating androgen levels in healthy women. Design: This was a randomized, controlled, crossover trial. Setting: The study was conducted at an endocrinology center. Patients: Patients included 12 healthy young women during the early follicular phase of two subsequent cycles. Intervention: After an overnight fast, a 20% lipid/heparin or a saline/heparin infusion was administered in random order for 330 min. Main Outcome Measures: A detailed characterization of androgen metabolism was performed. Results: Elevations in free fatty acids and triglycerides, induced by lipid/heparin infusion, elevates the le...

47 citations


Journal ArticleDOI
TL;DR: In PCOS, RBP4 has a small independent impact on IR and is not correlated with hyperandrogenemia, 17beta-estradiol, other adrenal steroids, or with markers of adiposity in general.
Abstract: Objective: Adiposity, insulin resistance (IR), and hyperandrogenism are features of polycystic ovary syndrome (PCOS). Retinol-binding protein 4 (RBP4) secreted from adipose and liver tissues has been linked to IR. The impact of RBP4 on IR in PCOS and its usability to identify women with metabolic syndrome (MS) or impaired glucose tolerance ((IGT) or diabetes) were investigated. Design: Plasma RBP4 was determined in 115 consecutive PCOS women. Associations with IR, body composition, and hyperandrogenemia were investigated by correlation and multiple linear regression analyses in 110 non-diabetics. Receiver operating characteristic curve analysis was used to evaluate RBP4 as a parameter for identifying MS and IGT or diabetes. Results: RBP4 increased over tertiles of IR (PZ0.009). RBP4 correlated with HOMA %S (RZK0.286, PZ 0.002), waist-to-hip ratio (WHR) (RZ0.233, PZ0.034), and dual energy X-ray absorptiometry (DEXA)-lean body mass (RZ0.282, PZ0.016) but not with body mass index (BMI), DEXA-total or trunk fat mass, hsCRP, free testosterone, DHEAS, androstenedione, and 17b-estradiol. Adjusted for age, BMI, smoking, and IGT, the association between RBP4 and HOMA %S remained significant (PZ0.032). RBP4 explained 4.6% of the variation in HOMA %S. RBP4 was higher in MS and IGT or diabetes, but its ability to identify these women was low (area under the curve, AUCZ0.631, PZ0.041 or AUCZ0.660, PZ0.016). Conclusions: In PCOS, RBP4 has a small independent impact on IR. It is not correlated with hyperandrogenemia, 17b-estradiol, other adrenal steroids, or with markers of adiposity in general. Furthermore, RBP4 does not appear suitable for screening MS or impaired glucose metabolism (IGT or diabetes).

30 citations


Journal ArticleDOI
04 Dec 2008-PLOS ONE
TL;DR: There is no strong effect of the common genetic variation within the SOCS3 gene on the development of type 2 diabetes, and no evidence for interaction with BMI or sex was found.
Abstract: Background The suppressor of cytokine signalling 3 (SOCS3) provides a link between cytokine action and their negative consequences on insulin signalling. Thus SOCS3 is a potential candidate gene for type 2 diabetes (T2DM).


Journal ArticleDOI
TL;DR: In this article, the authors examined small-scale precipitation patterns in a north-Alpine region, and their dependence on the freezing level and on the crest-level wind direction and speed.
Abstract: This study examines small-scale precipitation patterns in a north-Alpine region, and their dependence on the freezing level and on the crest-level (700 hPa) wind direction and speed On the one hand, measurements from a uniquely dense operational rain-gauge network are analyzed for a period of 15 years (1991--2005) Information on the ambient atmospheric fields was extracted from climate-mode MM5 simulations driven with ECMWF (re-analysis data On the other hand, high-resolution semi-idealized MM5 simulations have been conducted, combining realistic topography with idealized atmospheric fields The atmospheric flow parameters have been chosen to be representative of those used to classify the observational data, focusing on atmospheric conditions conducive to stratiform, orographically enhanced precipitation in the region under consideration The results of the data analysis indicate a pronounced tendency for local precipitation maxima in the lee of individual mountain ridges, whereas the variability between stations in the centre of wider valleys and stations on the windward foot of individual ridges is comparatively small This points towards a strong contribution of local precipitation enhancement due to the seeder--feeder mechanism, combined with downstream advection of the precipitating hydrometeors by the ambient winds The data analysis also reveals that strong winds and high temperatures tend to shift the precipitation field towards the interior of the Alps, whereas low temperatures and weak winds favour precipitation maxima near the northern edge of the Alps The semi-idealized simulations are consistent with these findings, but their quantitative agreement with the observed precipitation patterns depends on the ambient flow conditions The closest agreement is found for atmospheric conditions conducive to strong orographic lifting, for which our present idealized flow fields were designed Lower skill is obtained for conditions not dominated by orographic lifting, which implies that future work should include a generalization of the idealized flow fields Nevertheless, precipitation patterns generated with semi-idealized simulations seem to be very promising to support the spatial interpolation of point measurements (such as are needed for precipitation climatologies), which currently is usually based on statistical methods rather than physically motivated structures Copyright © 2008 Royal Meteorological Society

Journal ArticleDOI
TL;DR: The effect of KCNJ11 E23K on diabetes risk within a prospective case-cohort study of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort and the association between polymorphism and disposition index was investigated.
Abstract: Various cross-sectional studies suggest that a polymorphism (E23K) within the ATP-sensitive K+ channel KCNJ11 gene is associated with type 2 diabetes (1). However, only two prospective studies have addressed the relation between KCNJ11 E23K and type 2 diabetes, and these studies were intervention trials based on individuals with impaired fasting glucose and impaired glucose tolerance (2–4). With respect to functional effects, recent studies have been inconsistent regarding demonstration of a relation of the polymorphism with markers of insulin secretion (3,5,6), although in vitro studies clearly suggested a defect in insulin secretion (7–9). One study proposed a relation to glucagon response, while insulin secretion itself was not affected (10). However, the relation between polymorphism and insulin secretion might have been masked in some of those studies by differences of insulin sensitivity, and detailed analysis might thus require consideration of insulin sensitivity of the study participants, such as that given in the disposition index (11). We investigated the effect of KCNJ11 E23K on diabetes risk within a prospective case-cohort study ( n = 2,945) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. We additionally tested the association with diabetes in a second independent cross-sectional study, the Metabolic Syndrome Berlin Potsdam (MeSyBePo) cohort, from the same geographical region ( n = 1,891). Within this second study, the association between polymorphism and disposition index was additionally investigated. We designed a case-cohort study within the EPIC-Potsdam study, a prospective cohort involving 27,548 Caucasian volunteers, mainly aged 35–65 years, from the general population (12–14). A total of 2,263 individuals were randomly selected for a subcohort. Because the …

Journal ArticleDOI
TL;DR: Moderate hyperinsulinemic and hyper Insulinemic-hyperlipidemic clamp conditions differentially modulated circulating total ghrelin and acylghrelin in humans.
Abstract: Ghrelin is a powerful orexigenic gut hormone. Circulating concentrations of total ghrelin are downregulated by food intake in both acute and chronic hyperinsulinemic states. However, in blood des-acylated (des-acyl) ghrelin is the predominant form that has no orexigenic effects in humans. Circulating acyl-ghrelin has been shown to be suppressed post-prandially and by pharmacological hyperinsulinemia. However, up to now responses of circulating acyl-ghrelin to moderate hyperinsulinemic and hyperinsulinemic-hyperlipidemic clamp conditions have not been reported. Fourteen healthy subjects were investigated using two-stepped euglycemic-hyperinsulinemic clamps (40 mU insulin/m2/min; mean 148±7 min till steady state, followed by 300 min lipid/heparin infusion). Responses of total ghrelin and acyl-ghrelin were measured at timed intervals throughout the clamps. Des-acyl-ghrelin concentrations were calculated by subtraction. Total ghrelin significantly decreased vs baseline concentrations (819±92 vs 564±58 pg/ml, p<0.001), thereby confirming previous observations. Des-acyl ghrelin closely followed total ghrelin concentrations and significantly decreased vs baseline (772±92 vs 517±56 pg/ml, p<0.001). In contrast, neither euglycemic-hyperinsulinemia nor euglycemic-hyperinsulinemic-hyperlipidemia suppressed acyl-ghrelin below baseline concentrations throughout the clamps (46±3 vs 47±8 pg/ml, p=0.90). In conclusion, moderate hyperinsulinemic and hyperinsulinemic-hyperlipidemic clamp conditions differentially modulated circulating total ghrelin and acylghrelin in humans. Factors other than changes in insulin and lipid concentrations are likely to contribute to the previously reported post-prandial reduction of circulating acyl-ghrelin.

Journal ArticleDOI
TL;DR: It is demonstrated that uPAR expression in human monocytes/macrophages is differentially stimulated by FFA, and these effects are partially mediated by the p38 MAP-kinase signaling pathway.

Journal ArticleDOI
TL;DR: The results suggest that the -546 polymorphism in the PKCbeta promoter reduces promoter activity, which leads to a decreased expression of PKC beta2 and subsequently is associated with decreased peripheral insulin-dependent glucose uptake.

Journal ArticleDOI
TL;DR: The radial drift time projection chamber (TPC) as discussed by the authors was built and installed at the CERES/NA45 experiment at CERN SPS in the late nineties, with the objective to improve the momentum resolution of the spectrometer.
Abstract: The design, calibration, and performance of the first radial drift Time Projection Chamber (TPC) are presented. The TPC was built and installed at the CERES/NA45 experiment at the CERN SPS in the late nineties, with the objective to improve the momentum resolution of the spectrometer. The upgraded experiment took data twice, in 1999 and in 2000. After a detailed study of residual distortions a spatial resolution of 340 μ m in the azimuthal and 640 μ m in the radial direction was achieved, corresponding to a momentum resolution of Δ p / p = ( 1 % · p / GeV ) 2 + ( 2 % ) 2 .

Journal ArticleDOI
TL;DR: Novel findings are reported showing that circulating CCK markedly increased in the euglycemic-hyperinsulinemic state, possibly as a result of near-complete suppression of circulating free fatty acids.
Abstract: Aims: Functions of the gut hormone cholecystokinin (CCK) include an important role in the regulation of gastric emptying, postprandial glucose homeostasis, and postmeal satiety. Postprandial CCK responses are significantly blunted in type 2 diabetic patients by unknown mechanisms. We hypothesized that hyperinsulinemia and lipid infusion influence circulating levels of biologically active CCK. Methods: Eleven healthy subjects were studied in a cross-over design after 10-h overnight fasts, using euglycemic-hyperinsulinemic clamps for 443 min, with an additional infusion of lipid-heparin (1.25 ml·min−1) or saline (1.25 ml·min−1) for the last 300 min after constant plasma glucose levels were achieved. Results: Euglycemic-hyperinsulinemia resulted in a sustained, up to 5-fold increase of plasma CCK (P < 0.001). When adding lipid infusion instead of saline, CCK concentrations rapidly declined and returned to baseline levels (CCK300 min 1.1 ± 0.2 vs. 3.3 ± 0.3 pmol/liter, P < 0.001). Partial intraclass correlati...

Journal Article
TL;DR: The waist baseline (cm) 99.4±1.895.3±2.897.8±1-1.698.5 Waist baseline after LCD 36.2± 1.539.0±3.340.5 Body fat after LCD (%) 36.8 ±1.634.5±3,000.
Abstract: 39.6±1.540.0±1.439.4±1.340.2±1.539.3±1.5 Body fat after LCD (%) 36.8±1.634.2±1.835.3±1.435.6±1.735.7±1.5 Waist baseline (cm) 99.4±1.898.4±1.698.8±1.897.3±2.1100.6±1.8 Waist after LCD (cm) 96.6±1.695.1±1.697.4±1.895.9±1.897.9±1.9 RESULTS