Enhanced insulin sensitivity in skeletal muscle and liver by physiological overexpression of SIRT6

Objective: Available treatment for obesity and type 2 diabetes mellitus (T2DM) is suboptimal. Thus, identifying novel molecular target(s) exerting protective effects against these metabolic imbalances is of enormous medical significance. Sirt6 loss- and gain-of-function studies have generated confounding data regarding the role of this sirtuin on energy and glucose homeostasis, leaving unclear whether activation or inhibition of SIRT6 may be beneficial for the treatment of obesity and/or T2DM. Methods: To address these issues, we developed and studied a novel mouse model designed to produce eutopic and physiological overexpression of SIRT6 (Sirt6BAC mice). These mutants and their controls underwent several metabolic analyses. These include whole-blood reverse phase high-performance liquid chromatography assay, glucose and pyruvate tolerance tests, hyperinsulinemic-euglycemic clamp assays, and assessment of basal and insulin-induced level of phosphorylated AKT (p-AKT)/AKT in gastrocnemius muscle. Results: Sirt6BAC mice physiologically overexpress functionally competent SIRT6 protein. While Sirt6BAC mice have normal body weight and adiposity, they are protected from developing high-caloric-diet (HCD)-induced hyperglycemia and glucose intolerance. Also, Sirt6BAC mice display increased circulating level of the polyamine spermidine. The ability of insulin to suppress endogenous glucose production was significantly enhanced in Sirt6BAC mice compared to wild-type controls. Insulin-stimulated glucose uptake was increased in Sirt6BAC mice in both gastrocnemius and soleus muscle, but not in brain, interscapular brown adipose, or epididymal adipose tissue. Insulin-induced p-AKT/AKT ratio was increased in gastrocnemius muscle of Sirt6BAC mice compared to wild-type controls. Conclusions: Our data indicate that moderate, physiological overexpression of SIRT6 enhances insulin sensitivity in skeletal muscle and liver, engendering protective actions against diet-induced T2DM. Hence, the present study provides support for the anti-T2DM effect of SIRT6 and suggests SIRT6 as a putative molecular target for anti-T2DM treatment

Prospects for Payments for Ecosystem Services in the Brazilian Pantanal: A Scenario Analysis

The present study investigates the prospects for a large-scale implementation of Payments for Ecosystem Services (PES) schemes in the Brazilian Pantanal wetland. Despite increasing environmental threats associated with development pressures and the growing interest of public and private organizations, no PES schemes are currently in place in the Pantanal. Through an exploratory scenario analysis, this article determines the prospects for PES in the area. The findings suggest that a large-scale implementation is unlikely, as this would require much higher levels of environmental awareness among local decision makers and low substitution rates of ecosystem services by technology. Furthermore, strong socioeconomic inequality between inhabitants of the Pantanal lowlands and wealthy farmers of the neighboring uplands means that potential suppliers of ecosystem services would face very high opportunity costs to participate in PES schemes. The research findings are also relevant to other environmentally sensitive regions experiencing rapid economic growth and weak environmental regulation. </jats:p

Towards framing the global in Global Development: prospects for development geography

This paper examines data in the public sphere on the global scope of geography’s UKRI Global Challenges Research Fund (GCRF) projects. Building on decolonial critiques of development research, I argue that geography should frame ‘the global’ of global research as a sphere of ethical choices in research design and practice. The distribution of funded projects in the UKRI Gateway data suggests geographers succeed where they extend on the more worthy aspects of the discipline’s Area Studies legacy. The discipline’s engagements with Early Career Researchers, international colleagues, and the development sector, however, have potentially been reshaped by GCRF and thus need closer examination. While the UK government has brought the GCRF programme to a close, further work on these themes should inform the next iteration of global research. The ethical choices which make research global will remain fundamental to equitable design and impact in Global Development projects, thus scholars in development geography should prepare to make their projects more transparent and accountable

Spatial and temporal variation in reproduction of a generalist crocodilian, Caiman crocodilus yacare, in a seasonally flooded wetland

We monitored the number of caiman (Caiman crocodilus yacare) nests in two ranches in the Brazilian Pantanal that cover an area of about 50.000 ha for 28 years (1987-2014). The number of nests was related to combinations of rainfall, water level, and number of days with temperature below 20°C, depending on the area. Most of the variation in number of nests could not be predicted by the environmental variables, but could be represented mathematically by a sine wave. We were not able to identify any external driver and suspect that the regular fluctuations may have resulted from an intrinsic population process. Presently, ranches are used as management units under the legislation for ranching Pantanal caimans. However, although some breeding females were recaptured in the area after periods of up to 21 years, most were not recaptured near nests or in general surveys of the area, suggesting that females are not strongly philopatric and that ranches do not represent isolated demographic units. Copyright: © 2015 Campos et al