Erwin Schleicher - Academia.edu (original) (raw)

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Papers by Erwin Schleicher

Biotechnology Advances, 2019

Journal of nephrology

In a number of experimental models of nephropathy, heparin is renoprotective because it inhibits ... more In a number of experimental models of nephropathy, heparin is renoprotective because it inhibits mesangial matrix synthesis and cell proliferation; in most of these models, glomerular macrophage infiltration has a pathogenic role. We investigated the hypothesis that heparin might also be renoprotective by modulating the macrophages in various ways in the chronic puromycin glomerulosclerosis model. We studied the effect of a 3 month course, two different dosages of a non-anticoagulant heparin by immunohistochemical evaluation of the number of macrophages (ED-1 positive cells) in glomeruli, as well as the expression and deposition of TGF-beta and latent TGF-beta binding protein in foam cells and mesangial matrix. The renoprotective effect of heparin in this model was confirmed by our observation of lower urine protein and albumin excretion, and a reduced glomerular sclerosis score. These effects were associated with the prevention of macrophage glomerular infiltration, and the inhibit...

Encyclopedia of Molecular Mechanisms of Disease, 2009

Molecular Endocrinology, 2008

Transduction of the insulin signal is mediated by multisite Tyr and Ser/Thr phosphorylation of th... more Transduction of the insulin signal is mediated by multisite Tyr and Ser/Thr phosphorylation of the insulin receptor substrates (IRSs). Previous studies on the function of single-site phosphorylation, particularly phosphorylation of Ser-302, -307, and -318 of IRS-1, showed attenuating as well as enhancing effects on insulin action. In this study we investigated a possible cross talk of these opposedly acting serine residues in insulin-stimulated skeletal muscle cells by monitoring phosphorylation kinetics, and applying loss of function, gain of function, and combination mutants of IRS-1. The phosphorylation at Ser-302 was rapid and transient, followed first by Ser-318 phosphorylation and later by phosphorylation of Ser-307, which remained elevated for 120 min. Mutation of Ser-302 to alanine clearly reduced the subsequent protein kinase C-ζ-mediated Ser-318 phosphorylation. The Ser-307 phosphorylation was independent of Ser-302 and/or Ser-318 phosphorylation status. The functional con...

Journal of Biological Chemistry, 2004

Journal of Biological Chemistry, 2008

$Research paper thumbnail of Fatty Liver Is Independently Associated With Alterations in Circulating HDL2 and HDL3 Subfractions$

Diabetes Care, 2013

OBJECTIVE Nonalcoholic fatty liver (NAFL) is thought to contribute to insulin resistance and its ... more OBJECTIVE Nonalcoholic fatty liver (NAFL) is thought to contribute to insulin resistance and its metabolic complications. However, some individuals with NAFL remain insulin sensitive. Mechanisms involved in the susceptibility to develop insulin resistance in humans with NAFL are largely unknown. We investigated circulating markers and mechanisms of a metabolically benign and malignant NAFL by applying a metabolomic approach. RESEARCH DESIGN AND METHODS A total of 265 metabolites were analyzed before and after a 9-month lifestyle intervention in plasma from 20 insulin-sensitive and 20 insulin-resistant subjects with NAFL. The relevant plasma metabolites were then tested for relationships with insulin sensitivity in 17 subjects without NAFL and in plasma from 29 subjects with liver tissue samples. RESULTS The best separation of the insulin-sensitive from the insulin-resistant NAFL group was achieved by a metabolite pattern including the branched-chain amino acids leucine and isoleucin...

Diabetes Care, 2009

OBJECTIVE We investigated whether palmitoleate, which prevents insulin resistance in mice, predic... more OBJECTIVE We investigated whether palmitoleate, which prevents insulin resistance in mice, predicts insulin sensitivity in humans. RESEARCH DESIGN AND METHODS The fasting fatty acid pattern in the plasma free fatty acid (FFA) fraction was determined in 100 subjects at increased risk for type 2 diabetes. Insulin sensitivity was estimated during an oral glucose tolerance test (OGTT) at baseline and after 9 months of lifestyle intervention and measured during the euglycemic-hyperinsulinemic clamp (n = 79). RESULTS Circulating palmitoleate (OGTT:F ratio = 8.2, P = 0.005; clamp:F ratio = 7.8, P = 0.007) but not total FFAs (OGTT:F ratio = 0.6, P = 0.42; clamp:F ratio = 0.7, P = 0.40) correlated positively with insulin sensitivity, independently of age, sex, and adiposity. High baseline palmitoleate predicted a larger increase in insulin sensitivity. For 1-SD increase in palmitoleate, the odds ratio for being in the highest versus the lowest tertile of adjusted change in insulin sensitivit...

Diabetes Care, 2009

Clinical Chemistry and Laboratory Medicine, 1999

The prosclerotic transforming growth factor beta1 (TGF-beta1) is a key factor in the induction an... more The prosclerotic transforming growth factor beta1 (TGF-beta1) is a key factor in the induction and maintenance of fibrosis in different organs. To assess relative changes in TGF-beta1 mRNA levels, the comparative kinetic reverse transcription-polymerase chain reaction strategy was used. In this method, cellular mRNA levels of the target and a house-keeping gene are reverse transcribed, amplified by the polymerase chain reaction (PCR) and the kinetics of PCR amplification are compared. Since the current determination of the PCR products, using electrophoretic separation in polyacrylamide gel, staining and scanning of the gel, is time-consuming (&amp;gt; or = 5 hours) and inaccurate, we have developed a method using capillary gel electrophoresis (CGE) in combination with laser-induced fluorescence (LIF) detection for quantification of PCR-products. Using the CGE-LIF method, a minute aliquot of the PCR reaction mixture is separated and quantified within 10 min. Comparison of the values with those obtained by polyacrylamide gel electrophoresis demonstrates the improved sensitivity (&amp;gt; 1000 fold) and accuracy of the proposed method. The CGE-LIF procedure offers a convenient way of automated, comparative analysis of low levels of mRNA via reverse transcription PCR in low cell numbers or small amounts of tissue samples.

American Journal of Physiology-Endocrinology and Metabolism, 2010

The identity of specific serine phosphorylation residues of insulin receptor substrate (IRS)-2 an... more The identity of specific serine phosphorylation residues of insulin receptor substrate (IRS)-2 and their impact on insulin signal transduction are largely unknown. Ser675and Ser907of mouse IRS-2 are adjacent to PI 3-kinase or Grb2 binding domains, respectively. Using monoclonal phosphosite-specific antibodies, we demonstrated the phosphorylation of both serines after stimulation of Fao hepatoma cells with insulin, anisomycin, or phorbol esters. Phosphorylation of both sites was a late and prolonged event during insulin treatment and was also detected in liver tissue of insulin-treated as well as refed mice. Inhibition and siRNA-mediated knockdown of ERK1/2 indicated that the insulin-induced phosphorylation of Ser907was ERK dependent. Phosphorylation of Ser907did not prevent the insulin-induced association of IRS-2 with Grb2, but phosphorylation of the adjacent Tyr911was proved to be crucial in HEK 293 cells expressing IRS-2 Ala mutants. The insulin-induced phosphorylation of Ser675w...