Ras Inhibition Induces Insulin Sensitivity and Glucose Uptake

BACKGROUND: Reduced glucose uptake due to insulin resistance is a pivotal mechanism in the pathogenesis of type 2 diabetes. It is also associated with increased inflammation. Ras inhibition downregulates inflammation in various experimental models. The aim of this study was to examine the effect of Ras inhibition on insulin sensitivity and glucose uptake, as well as its influence on type 2 diabetes development. METHODS AND FINDINGS: The effect of Ras inhibition on glucose uptake was examined both in vitro and in vivo. Ras was inhibited in cells transfected with a dominant-negative form of Ras or by 5-fluoro-farnesylthiosalicylic acid (F-FTS), a small-molecule Ras inhibitor. The involvement of IκB and NF-κB in Ras-inhibited glucose uptake was investigated by immunoblotting. High fat (HF)-induced diabetic mice were treated with F-FTS to test the effect of Ras inhibition on induction of hyperglycemia. Each of the Ras-inhibitory modes resulted in increased glucose uptake, whether in insulin-resistant C2C12 myotubes in vitro or in HF-induced diabetic mice in vivo. Ras inhibition also caused increased IκB expression accompanied by decreased expression of NF-κB . In fat-induced diabetic mice treated daily with F-FTS, both the incidence of hyperglycemia and the levels of serum insulin were significantly decreased. CONCLUSIONS: Inhibition of Ras apparently induces a state of heightened insulin sensitization both in vitro and in vivo. Ras inhibition should therefore be considered as an approach worth testing for the treatment of type 2 diabetes

The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats

The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well

Can static habitat protection encompass critical areas for highly mobile marine top predators? Insights from coastal East Africa

© 2015 Pérez-Jorge et al. Along the East African coast, marine top predators are facing an increasing number of anthropogenic threats which requires the implementation of effective and urgent conservation measures to protect essential habitats. Understanding the role that habitat features play on the marine top predator' distribution and abundance is a crucial step to evaluate the suitability of an existing Marine Protected Area (MPA), originally designated for the protection of coral reefs. We developed species distribution models (SDM) on the IUCN data deficient Indo-Pacific bottlenose dolphin (Tursiops aduncus) in southern Kenya. We followed a comprehensive ecological modelling approach to study the environmental factors influencing the occurrence and abundance of dolphins while developing SDMs. Through the combination of ensemble prediction maps, we defined recurrent, occasional and unfavourable habitats for the species. Our results showed the influence of dynamic and static predictors on the dolphins' spatial ecology: dolphins may select shallow areas (5-30 m), close to the reefs (< 500 m) and oceanic fronts (< 10 km) and adjacent to the 100m isobath (< 5 km).We also predicted a significantly higher occurrence and abundance of dolphins within the MPA. Recurrent and occasional habitats were identified on large percentages on the existing MPA (47% and 57% using presence-absence and abundance models respectively). However, the MPA does not adequately encompass all occasional and recurrent areas and within this context, we propose to extend the MPA to incorporate all of them which are likely key habitats for the highly mobile species. The results from this study provide two key conservation and management tools: (i) an integrative habitat modelling approach to predict key marine habitats, and (ii) the first study evaluating the effectiveness of an existing MPA for marine mammals in the Western Indian Ocean. Copyright:ML was funded by a Juan de la Cierva postdoctoral contract (JCI-2010-07639, Spanish Ministry of Science and Innovation - http://www.idi.mineco.gob.es/) and a Ramón y Cajal postdoctoral contract (RYC-2012-09897). Funds were partially provided by a grant from the Spanish Ministry of Economy - http://www.idi.mineco.gob.es/ (CGL2013-42203-R)Peer Reviewe