11 beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle

OBJECTIVE: Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity. \ud RESEARCH DESIGN AND METHODS: Rodent and human cell cultures, whole-tissue explants, and animal models were used to determine the impact of glucocorticoids and selective 11beta-HSD1 inhibition upon insulin signaling and action. \ud RESULTS: Dexamethasone decreased insulin-stimulated glucose uptake, decreased IRS1 mRNA and protein expression, and increased inactivating pSer$^{307}$ insulin receptor substrate (IRS)-1. 11beta-HSD1 activity and expression were observed in human and rodent myotubes and muscle explants. Activity was predominantly oxo-reductase, generating active glucocorticoid. A1 (selective 11beta-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer$^{307}$ IRS1 and reduction in total IRS1 protein after treatment with 11DHC but not corticosterone. In C57Bl6/J mice, the selective 11beta-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin sensitivity. In KK mice treated with A2, skeletal muscle pSer$^{307}$ IRS1 decreased and pThr$^{308}$ Akt/PKB increased. In addition, A2 decreased both lipogenic and lipolytic gene expression.\ud CONCLUSIONS: Prereceptor facilitation of glucocorticoid action via 11beta-HSD1 increases pSer$^{307}$ IRS1 and may be crucial in mediating insulin resistance in skeletal muscle. Selective 11beta-HSD1 inhibition decreases pSer$^{307}$ IRS1, increases pThr$^{308}$ Akt/PKB, and decreases lipogenic and lipolytic gene expression that may represent an important mechanism underpinning their insulin-sensitizing action

11 beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle

OBJECTIVE: Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity. \ud RESEARCH DESIGN AND METHODS: Rodent and human cell cultures, whole-tissue explants, and animal models were used to determine the impact of glucocorticoids and selective 11beta-HSD1 inhibition upon insulin signaling and action. \ud RESULTS: Dexamethasone decreased insulin-stimulated glucose uptake, decreased IRS1 mRNA and protein expression, and increased inactivating pSer$^{307}$ insulin receptor substrate (IRS)-1. 11beta-HSD1 activity and expression were observed in human and rodent myotubes and muscle explants. Activity was predominantly oxo-reductase, generating active glucocorticoid. A1 (selective 11beta-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer$^{307}$ IRS1 and reduction in total IRS1 protein after treatment with 11DHC but not corticosterone. In C57Bl6/J mice, the selective 11beta-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin sensitivity. In KK mice treated with A2, skeletal muscle pSer$^{307}$ IRS1 decreased and pThr$^{308}$ Akt/PKB increased. In addition, A2 decreased both lipogenic and lipolytic gene expression.\ud CONCLUSIONS: Prereceptor facilitation of glucocorticoid action via 11beta-HSD1 increases pSer$^{307}$ IRS1 and may be crucial in mediating insulin resistance in skeletal muscle. Selective 11beta-HSD1 inhibition decreases pSer$^{307}$ IRS1, increases pThr$^{308}$ Akt/PKB, and decreases lipogenic and lipolytic gene expression that may represent an important mechanism underpinning their insulin-sensitizing action

Antarctic Climate Change and the Environment

The Antarctic climate system varies on timescales from orbital, through millennial to sub-annual, and is closely coupled to other parts of the global climate system. We review these variations from the perspective of the geological and glaciological records and the recent historical period from which we have instrumental data (the last 50 years). We consider their consequences for the biosphere, and show how the latest numerical models project changes into the future, taking into account human actions in the form of the release of greenhouse gases and chlorofluorocarbons into the atmosphere. In doing so, we provide an essential Southern Hemisphere companion to the Arctic Climate Impact Assessment

The Antarctic Peninsula Under a 1.5 degrees C Global Warming Scenario

Warming of the Antarctic Peninsula in the latter half of the twentieth century was greater than any other terrestrial environment in the Southern Hemisphere, and clear cryospheric and biological consequences have been observed. Under a global 1.5°C scenario, warming in the Antarctic Peninsula is likely to increase the number of days above 0°C, with up to 130 of such days each year in the northern Peninsula. Ocean turbulence will increase, making the circumpolar deep water (CDW) both warmer and shallower, delivering heat to the sea surface and to coastal margins. Thinning and recession of marine margins of glaciers and ice caps is expected to accelerate to terrestrial limits, increasing iceberg production, after which glacier retreat may slow on land. Ice shelves will experience continued increase in meltwater production and consequent structural change, but not imminent regional collapses. Marine biota can respond in multiple ways to climatic changes, with effects complicated by past resource extraction activities. Southward distribution shifts have been observed in multiple taxa during the last century and these are likely to continue. Exposed (ice free) terrestrial areas will expand, providing new habitats for native and non-native organisms, but with a potential loss of genetic diversity. While native terrestrial biota are likely to benefit from modest warming, the greatest threat to native biodiversity is from non-native terrestrial species

Slogging and Stumbling Toward Social Justice in a Private Elementary School: The Complicated Case of St. Malachy

This case study examines St. Malachy, an urban Catholic elementary school primarily serving children traditionally marginalized by race, class, linguistic heritage, and disability. As a private school, St. Malachy serves the public good by recruiting and retaining such traditionally marginalized students. As empirical studies involving Catholic schools frequently juxtapose them with public schools, the author presents this examination from a different tack. Neither vilifying nor glorifying Catholic schooling, this study critically examines the pursuit of social justice in this school context. Data gathered through a 1-year study show that formal and informal leaders in St. Malachy adapted their governance, aggressively sought community resources, and focused their professional development to build the capacity to serve their increasingly pluralistic student population. The analysis confirms the deepening realization that striving toward social justice is a messy, contradictory, and complicated pursuit, and that schools in both public and private sectors are allies in this pursuit

Filosofía ambiental de campo: Educación e investigación para la valoración ecológica y ética de los insectos dulceacuícolas (Field environmental philosophy: education and research for the ecological and ethical appreciation of freshwater insects)

In a rapidly changing world, to confront biodiversity losses and the lack of appreciation for and knowledge about the most diverse groups of organisms, it is urgently necessary to stimulate cultural shifts that transcend purely scientific and technological domains. This paper addresses this problem by focusing on one of the least known groups of organisms, and in one of the most remote regions of the planet: freshwater insects in the sub-Antarctic Magellanic ecoregion. The work of this thesis included scientific-ecological and environmental philosophical research that was integrated into formal and non-formal environmental education practices that value freshwater insects, particularly as indicators of climate change. The integration of science and philosophy was done adapting the Field Environmental Philosophy methodology that includes a four-step cycle. Transdisciplinary research on freshwater insects and their sub-Antarctic ecosystems served as a basis for the composition of metaphors and educational activities with schoolchildren, other members of the local community and visitors to Omora Park, in Puerto Williams, Chile. Based on this work, new outdoor educational activities were designed with the objective of awakening the interest of citizens for insects, and nurturing their perceptions about these organisms, their habitats and life habits. In this way, at a local scale this work aims to contribute to greater knowledge, appreciation and conservation of this unique sub-Antarctic biodiversity, and at a global scale it aims to contribute overcoming the under-appreciation for the most diverse group of organisms: the insects

Cross-Disciplinarity in the Advance of Antarctic Ecosystem Research

The biodiversity, ecosystem services and climate variability of the Antarctic continent, and the Southern Ocean are major components of the whole Earth system. Antarctic ecosystems are driven more strongly by the physical environment than many other marine and terrestrial ecosystems. As a consequence, to understand ecological functioning, cross-disciplinary studies are especially important in Antarctic research. The conceptual study presented here is based on a workshop initiated by the Research Programme Antarctic Thresholds - Ecosystem Resilience and Adaption of the Scientific Committee on Antarctic Research, which focused on challenges in identifying and applying cross-disciplinary approaches in the Antarctic. Novel ideas, and first steps in their implementation, were clustered into eight themes, ranging from scale problems, risk maps, organism and ecosystem responses to multiple environmental changes, to evolutionary processes. Scaling models and data across different spatial and temporal scales were identified as an overarching challenge. Approaches to bridge gaps in the research programmes included multi-disciplinary monitoring, linking biomolecular findings and simulated physical environments, as well as integrative ecological modelling. New strategies in academic education are proposed. The results of advanced cross-disciplinary approaches can contribute significantly to our knowledge of ecosystem functioning, the consequences of climate change, and to global assessments that ultimately benefit humankind

An expert-driven framework for applying eDNA tools to improve biosecurity in the Antarctic

Signatories to the Antarctic Treaty System’s Environmental Protocol are committed to preventing incursions of non-native species into Antarctica, but systematic surveillance is rare. Environmental DNA (eDNA) methods provide new opportunities for enhancing detection of non-native species and biosecurity monitoring. To be effective for Antarctic biosecurity, eDNA tests must have appropriate sensitivity and specificity to distinguish non-native from native Antarctic species, and be fit-for-purpose. This requires knowledge of the priority risk species or taxonomic groups for which eDNA surveillance will be informative, validated eDNA assays for those species or groups, and reference DNA sequences for both target non-native and related native Antarctic species. Here, we used an expert elicitation process and decision-by-consensus approach to identify and assess priority biosecurity risks for the Australian Antarctic Program (AAP) in East Antarctica, including identifying high priority non-native species and their potential transport pathways. We determined that the priority targets for biosecurity monitoring were not individual species, but rather broader taxonomic groups such as mussels (Mytilus species), tunicates (Ascidiacea), springtails (Collembola), and grasses (Poaceae). These groups each include multiple species with high risks of introduction to and/or establishment in Antarctica. The most appropriate eDNA methods for the AAP must be capable of detecting a range of species within these high-risk groups (e.g., eDNA metabarcoding). We conclude that the most beneficial Antarctic eDNA biosecurity applications include surveillance of marine species in nearshore environments, terrestrial invertebrates, and biofouling species on vessels visiting Antarctica. An urgent need exists to identify suitable genetic markers for detecting priority species groups, establish baseline terrestrial and marine biodiversity for Antarctic stations, and develop eDNA sampling methods for detecting biofouling organisms

An expert-driven framework for applying eDNA tools to improve biosecurity in the Antarctic

Signatories to the Antarctic Treaty System’s Environmental Protocol are committed to preventing incursions of non-native species into Antarctica, but systematic surveillance is rare. Environmental DNA (eDNA) methods provide new opportunities for enhancing detection of non-native species and biosecurity monitoring. To be effective for Antarctic biosecurity, eDNA tests must have appropriate sensitivity and specificity to distinguish non-native from native Antarctic species, and be fit-for-purpose. This requires knowledge of the priority risk species or taxonomic groups for which eDNA surveillance will be informative, validated eDNA assays for those species or groups, and reference DNA sequences for both target non-native and related native Antarctic species. Here, we used an expert elicitation process and decision-by-consensus approach to identify and assess priority biosecurity risks for the Australian Antarctic Program (AAP) in East Antarctica, including identifying high priority non-native species and their potential transport pathways. We determined that the priority targets for biosecurity monitoring were not individual species, but rather broader taxonomic groups such as mussels (Mytilus species), tunicates (Ascidiacea), springtails (Collembola), and grasses (Poaceae). These groups each include multiple species with high risks of introduction to and/or establishment in Antarctica. The most appropriate eDNA methods for the AAP must be capable of detecting a range of species within these high-risk groups (e.g., eDNA metabarcoding). We conclude that the most beneficial Antarctic eDNA biosecurity applications include surveillance of marine species in nearshore environments, terrestrial invertebrates, and biofouling species on vessels visiting Antarctica. An urgent need exists to identify suitable genetic markers for detecting priority species groups, establish baseline terrestrial and marine biodiversity for Antarctic stations, and develop eDNA sampling methods for detecting biofouling organisms.This work was supported as a Science Innovation Project by the Department of Agriculture, Water and the Environment’s Science Innovation Program funding 2021–22 (project team: A.J.M., L.J.C., D.M.B., C.K.K., J.S.S. and L.S.). Support was also provided (to J.D.S, E.L.J., S.A.R., J.S.S., M.I.S., J.M.S., N.G.W.) from Australian Research Council SRIEAS grant SR200100005. P.C. and K.A.H. are supported by NERC core funding to the BAS Biodiversity, Evolution and Adaptation Team and Environment Office, respectively. L.R.P. and M.G. are supported by Biodiversa ASICS funding