701 research outputs found
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
Recommended from our members
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
Circular consumption to reduce environmental pressure:Potential of behavioural change in the Netherlands
The European Union and various individual countries strive for a more circular economy to reduce environmental pressure. The transition towards a circular economy requires a change in what and how we consume. We argue that a realistic estimation of the environmental mitigation potential depends on 1) the environmental benefit that results from a certain circular behaviour, referred to as the ātheoretical reduction potentialā (TRP), and 2) the behavioural plasticity, reflecting the share of consumers who are not yet engaging in the behaviour but would be willing to do so if circular goods and services are easily accessible and affordable. The aim of this study was to provide insight into the environmental mitigation potential of circular consumer behaviour by assessing both their TRP and behavioural plasticity. To do so, we conducted a large-scale survey in the Netherlands (n = 2542) in which we examined the current adoption rate and willingness of consumers to engage in 92 circular consumer behaviours. Furthermore, we made a rough estimate of the TRP of these behaviours in terms of greenhouse gas emissions and land use. Our results show that many behaviours with a large TRP (mainly related to consuming less and saving energy) have a rather low behavioural plasticity, either because most consumers are not willing to adopt such a behaviour or because they are already engaging in it. Behavioural plasticity is relatively high when it comes to prolonging product lifetimes and purchasing more sustainable product alternatives, but these behaviours tend to have a relatively small TRP. Our findings demonstrate that the TRP is a limited indicator of the actual environmental mitigation potential of circular consumer behaviour and suggest that behavioural plasticity is an important additional indicator to identify the types of behaviour relevant for research and policymaking.</p
Der Online-Test BULATS Deutsch - ein geeignetes Instrument zur Messung von Lernfortschritten? Erste Ergebnisse im Rahmen des Projekts "Tablet-Klasse"
- ā¦