Genetic Analysis of Insulin and Insulin-like Growth Factor-1 Signaling in the Central Nervous System

Much of our understanding about insulin has been gained from murine knockouts of the insulin receptor (IR) gene in the whole body or restricted to individual tissues. Here, two novel inducible mouse models with IR inactivation in all tissues including brain (IRwb) or restricted to peripheral tissues (IRper) are described. Crucially, mouse models with inducible deletion later in life allow for the distinction between developmental and acute effects of insulin resistance. Compared to IRper mice, body wide deletion of IR has a more pronounced effect on reducing white adipose tissue mass (WAT), despite a similar reduction in IR expression in WAT of both models. The more pronounced lipodystrophy in IRwb mice points to a novel regulatory function of central insulin receptor signaling in control of lipogenesis which is substantiated by the ability of intracerebroventricularly applied insulin in C57BL/6 mice to slightly increase adipocyte size, fat mass and white adipose tissue lipoprotein lipase expression. Moreover, loss of insulin receptor signaling in adipocytes results in an increase in leptin secretion from the adipose tissue, indicating that insulin inhibits adipocyte-autonomous leptin secretion. In addition to the increase in leptin secretion, both strains display a dramatic upregulation of hepatic leptin receptor expression, while only IRper mice exhibit increased Stat-3 phosphorylation and IL-6 expression. IRwb mice, on the other hand, display a higher degree of impaired peripheral glucose metabolism, which is ameliorated by leptin administration along with Stat-3 phosphorylation. Furthermore, despite exhibiting largely reduced IR expression in pancreas, IRper mice still secrete insulin in response to an acute glucose challenge, whereas glucose-stimulated insulin secretion is abrogated in IRwb mice, but both mouse models respond to hyperglycemia with a significant increase in beta cell mass. In conclusion, these findings define CNS insulin action as a pivotal determinant of energy homeostasis and peripheral glucose metabolism in the adult mouse and support recent findings on the regulation of hepatic IL-6 mRNA by central insulin. Nevertheless, leptin-activated Stat-3 phosphorylation in liver may alternatively lead to improved glucose metabolism in IRwb mice. Furthermore, deletion of the insulin-like growth factor (IGF-) 1 receptor in the central nervous system reveals a significant role for IGF-1 receptor signaling in hippocampal learning and spatial memory acquisition and defines IGF-1R as a potential new therapeutic target in the treatment of conditions linked to anxiety-like behavior

Population Studies of Ulmus Crassifolia in Flood-Plain Forests of Denton County, Texas

The problem with which this investigation was concerned was the comparison of cedar elm populations in different stands along creeks in Denton County, Texas, and the relationship of certain population parameters to various substrates present at stand sites, Parameters investigated eluded average basal area, basal-area density, transect-segment density, intertree distance, lateral distance, frequency, diameter breast-high, diameter breast-high size-class distribution, and immature-tree density. Variations among populations of Ulmus crassifolia Nutt were noted and analyzed in terms of soil particle size and existing community conditions

CMC Materials for Aircraft Brakes

Übersucht zur Herstellung von C/C-SiC und dessen Werkstoffeigenschaften. Entwicklung von Reibbelägen für Airbus A 400M. Neue Preformtechniken und Sandwichsrukturen für Bremsscheiben

Der Online-Test BULATS Deutsch - ein geeignetes Instrument zur Messung von Lernfortschritten? Erste Ergebnisse im Rahmen des Projekts "Tablet-Klasse"

Im Herbst/Winter 2013 wurde an drei Goethe-Instituten in der Region Nordwesteuropa der Einsatz von Tablets im Fremdsprachenunterricht pilotiert und innerhalb eines Forschungsprojekts wissenschaftlich begleitet und evaluiert. Es wurde analysiert, ob Tablets (hier iPads) für das Fremdsprachenlernen Potentiale bieten, besonders bei der Förderung des Hörverstehens und des Sprechens. Die Lernenden wurden für die Untersuchung in zwei Gruppen aufgeteilt: Eine Gruppe arbeitete mit Tablets im Unterricht (N=27), die andere ohne (N=21). Die Veränderungen im Bereich Hörverstehen wurde in beiden Gruppen durch einen Vor- und Nachtest mit dem BULATS Online-Test Deutsch gemessen. Die Testergebnisse wurden anschließend miteinander verglichen. Es blieb zunächst offen, ob die Tablets tatsächlich zu einer Verbesserung in bestimmten Bereichen des Fremdsprachenlernens führen oder ob eventuell durch den Fokus auf die Technik mit weniger Lernfortschritt oder einer Verschlechterung zu rechnen ist. Im Verlauf des Projekts zeigte sich, dass die Testgruppe (Tablet-Gruppe) erkennbar bessere Werte im BULATS-Test erzielte als die Kontrollgruppe

RESVERATROL ATTENUATES EXERCISE-INDUCED ADAPTIVE RESPONSES IN RATS SELECTIVELY BRED FOR LOW RUNNING PERFORMANCE

Low capacity runner (LCR) rats have been developed by divergent artificial selection for treadmill endurance capacity to explore an aerobic biology-disease connection. The beneficial effects of resveratrol supplementation have been demonstrated in endurance running. In this study it was examined whether 12 weeks of treadmill exercise training and/or resveratrol can retrieve the low running performance of the LCR and impact mitochondrial biogenesis and quality control. Resveratrol regressed running performance in trained LCR (p\u3c0.05). Surprisingly, exercise and resveratrol treatments significantly decreased pAMPK/AMPK, SIRT1, SIRT4, forkhead transcription factor 1 (FOXO1) and mitochondrial transcription factor A (TFAM) levels in these animals (p\u3c0.05). Mitochondrial fusion protein, HSP78 and polynucleotide phosphorylase were significantly induced in LCR-trained, LCR-resveratrol treated, LCR-trained and resveratol treated groups compared to LCR-controls. The data indicate that the AMPK-SIRT1-NAMPTFOXO1 axis could be important to the limited aerobic endurance capacity of low running capacity rats. Resveratrol supplementation was not beneficial in terms of aerobic endurance performance, mitochondrial biogenesis, or quality control