Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat

Aims/hypothesis: In vitro studies point to a toxic effect of high glucose and non-esterified fatty acids on beta cells. Whether elevated levels of glucose and lipids induce beta cell loss in vivo is less clear. The domestic cat has recently been proposed as a valuable animal model for human type 2 diabetes because feline diabetes shows several similarities with diabetes in humans, including obesity-induced insulin resistance, impaired beta cell function, decreased number of beta cells and pancreatic amyloid deposition. Methods: We infused healthy cats with glucose or lipids for 10days to clamp their blood concentrations at the approximate level found in untreated feline diabetes (glucose: 25-30mmol/l; triacylglycerols: 3-7mmol/l). Results: Glucose and lipid levels were adequately targeted. Plasma non-esterified fatty acids were increased by lipid infusion 1.7-fold. A dramatic and progressive decline of plasma insulin levels was observed in glucose-infused cats beginning after 2days of hyperglycaemic clamp. In contrast, plasma insulin concentration and glucose tolerance test were not affected by hyperlipidaemia. Compared with controls, glucose-infused cats had a 50% decrease in beta cells per pancreatic area. Apoptotic islet cells and cleaved caspase-3-positive beta cells were observed in glucose-infused cats only. Conclusions/interpretation: Sustained hyperglycaemia but not hyperlipidaemia induces early and severe beta cell dysfunction in cats, and excess glucose causes beta cell loss via apoptosis in vivo. Hyperglycaemic clamps in cats may provide a good model to study the pathogenesis of glucose toxicity in beta cell

Comparison of a continuous glucose monitoring system with a portable blood glucose meter to determine insulin dose in cats with diabetes mellitus.

Background:The continuous glucose monitoring system (CGMS) Guardian REAL‐Time® allows the generation of very detailed glucose profiles in cats. The performance of CGMS to generate short‐term glucose profiles to evaluate treatment response has not been yet evaluated in diabetic cats.Hypothesis:Analysis of glucose profiles generated using the CGMS produces insulin dose recommendations that differ from those of profiles generated using the portable blood glucose meter (PBGM) in diabetic cats.Animals:Thirteen client‐owned diabetic cats.Methods:Prospective, observational study. Simultaneous glucose profiles were generated over an 8‐10 hour period using the CGMS, blood glucose concentration was measured every 2 hours with the PBGM. Profiles were submitted to three internal medicine specialists who used them to determine the insulin dose. Differences between insulin doses deduced from paired profiles were compared. Percentages of nadirs recorded with the CGMS that were lower, higher, or equal to those derived with the PBGM were calculated.Results:Twenty‐one paired glucose profiles were obtained. There was no difference of insulin doses based on CGMS and PBGM profiles (median 0 U; range: −1 to +0.5). Treatment decisions did not differ among investigators. Compared with the observed PBGM nadir, the CGMS nadir was lower, higher, or equal in 17, 2, and 2 of 21 cases, respectively.Conclusions and Clinical Importance:Adjustments in insulin dose based on glucose profiles generated with the CGMS are similar to those based on the PBGM. The common occurrence of lower nadirs recorded with the CGMS suggests that this device detects hypoglycemic periods that are not identified with the PBGM

Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat

AIMS/HYPOTHESIS: In vitro studies point to a toxic effect of high glucose and non-esterified fatty acids on beta cells. Whether elevated levels of glucose and lipids induce beta cell loss in vivo is less clear. The domestic cat has recently been proposed as a valuable animal model for human type 2 diabetes because feline diabetes shows several similarities with diabetes in humans, including obesity-induced insulin resistance, impaired beta cell function, decreased number of beta cells and pancreatic amyloid deposition. METHODS: We infused healthy cats with glucose or lipids for 10 days to clamp their blood concentrations at the approximate level found in untreated feline diabetes (glucose: 25-30 mmol/l; triacylglycerols: 3-7 mmol/l). RESULTS: Glucose and lipid levels were adequately targeted. Plasma non-esterified fatty acids were increased by lipid infusion 1.7-fold. A dramatic and progressive decline of plasma insulin levels was observed in glucose-infused cats beginning after 2 days of hyperglycaemic clamp. In contrast, plasma insulin concentration and glucose tolerance test were not affected by hyperlipidaemia. Compared with controls, glucose-infused cats had a 50% decrease in beta cells per pancreatic area. Apoptotic islet cells and cleaved caspase-3-positive beta cells were observed in glucose-infused cats only. CONCLUSIONS/INTERPRETATION: Sustained hyperglycaemia but not hyperlipidaemia induces early and severe beta cell dysfunction in cats, and excess glucose causes beta cell loss via apoptosis in vivo. Hyperglycaemic clamps in cats may provide a good model to study the pathogenesis of glucose toxicity in beta cells

Diabetic cats have decreased gut microbial diversity and a lack of butyrate producing bacteria

none11noneKieler, Ida Nordang*; Osto, Melania; Hugentobler, Leoni; Puetz, Lara; Gilbert, M. Thomas P.; Hansen, Torben; Pedersen, Oluf; Reusch, Claudia E.; Zini, Eric; Lutz, Thomas A.; Bjørnvad, Charlotte ReinhardKieler, Ida Nordang; Osto, Melania; Hugentobler, Leoni; Puetz, Lara; Gilbert, M. Thomas P.; Hansen, Torben; Pedersen, Oluf; Reusch, Claudia E.; Zini, Eric; Lutz, Thomas A.; Bjørnvad, Charlotte Reinhar

Endothelial dysfunction in COVID-19: a position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science

The COVID-19 pandemic is an unprecedented healthcare emergency causing mortality and illness across the world. Although primarily affecting the lungs, the SARS-CoV-2 virus also affects the cardiovascular system. In addition to cardiac effects, e.g. myocarditis, arrhythmias, and myocardial damage, the vasculature is affected in COVID-19, both directly by the SARS-CoV-2 virus, and indirectly as a result of a systemic inflammatory cytokine storm. This includes the role of the vascular endothelium in the recruitment of inflammatory leucocytes where they contribute to tissue damage and cytokine release, which are key drivers of acute respiratory distress syndrome (ARDS), in disseminated intravascular coagulation, and cardiovascular complications in COVID-19. There is also evidence linking endothelial cells (ECs) to SARS-CoV-2 infection including: (i) the expression and function of its receptor angiotensin-converting enzyme 2 (ACE2) in the vasculature; (ii) the prevalence of a Kawasaki disease-like syndrome (vasculitis) in COVID-19; and (iii) evidence of EC infection with SARS-CoV-2 in patients with fatal COVID-19. Here, the Working Group on Atherosclerosis and Vascular Biology together with the Council of Basic Cardiovascular Science of the European Society of Cardiology provide a Position Statement on the importance of the endothelium in the underlying pathophysiology behind the clinical presentation in COVID-19 and identify key questions for future research to address. We propose that endothelial biomarkers and tests of function (e.g. flow-mediated dilatation) should be evaluated for their usefulness in the risk stratification of COVID-19 patients. A better understanding of the effects of SARS-CoV-2 on endothelial biology in both the micro- and macrovasculature is required, and endothelial function testing should be considered in the follow-up of convalescent COVID-19 patients for early detection of long-term cardiovascular complications

Melt pond biogeochemistry in central Arctic: first insights from MOSAiC campaign

We undertook a melt pond survey during the international drift campaign MOSAiC Leg 5 (from 22 August to 18 September 2020) to understand variations in climate gases (CO2, CH4, N2O and DMS) and nutrients in melt ponds during the open water and freezing periods, and to study the interactions with atmospheric and ecological parameters (Figure 1a). Inside those melt ponds with a darker color, we found significant quantities of floating organic material within the pond water, along with significant further organic material settled at the bottom of the pond and frozen into the ice (Figure 1b). These floating and sedimented materials were both white and green/brown; the green/brown material was mainly composed of phytoplankton “Melosira arctica”, while the white material was composed of re-mineralized organic matter during degradation (including the remains of krill and other zooplankton). There were strong vertical gradients in physical parameters from the surface to the bottom of the melt pond (within 1 m depth): from +0.2°C to –1.5°C for temperature, from 0 to 29 psu for salinity, and 9.2 to 13.5 mg L–1 for dissolved oxygen (DO). The DO minimum layer (below 9 mg L–1) corresponded with a salinity of 25 psu, which generally occurred at approximately 0.6 m depth, and it increased to over 13 mg L–1 at the atmospheric interface. At the end of Leg 5 (mid-September 2020), these strong gradients disappeared, likely due to the mixing events during the cooling and freezing periods. Prior to and during the freezing period, CO2 flux was measured periodically within the melt pond with a floating chamber system. Because measured in situ CO2 concentration at the melt pond surface (top 10 cm) was low (321 ppm) compared to the atmosphere (approximately 400 ppm), air–to-melt pond CO2 flux was negative (melt pond was acting as a sink for atmospheric CO2) around –3.9 mmol m–2 day–1. Therefore, the melt pond water absorbs significant amounts of CO2 from the atmosphere. We also found extremely low CO2 concentrations (170 ppm) at the freshwater/seawater interface (0.6 m depth) corresponding to the same depth as the DO minimum. Therefore, we expected that if melt pond water is mixed vertically by the wind, cooling, crack formation, and ice movement, the melt pond could become an even stronger sink for atmospheric CO2. Ice cores collected from the bottom of the melt pond were porous at the top 0.50 m, and contain large quantities of organic material similar to that identified floating in the water column This accumulation of material and ongoing degradation processes over the pond bottom ice would contribute significantly to the turnover of carbon, sulphur and nitrogen containing gases cycles within melt pond water and thereby gas exchange process with the atmosphere.MOSAi

Epigenetics in the primary and secondary prevention of cardiovascular disease: influence of exercise and nutrition

Increasing evidence links changes in epigenetic systems, such as DNA methylation, histone modification, and non-coding RNA expression, to the occurrence of cardiovascular disease (CVD). These epigenetic modifications can change genetic function under influence of exogenous stimuli and can be transferred to next generations, providing a potential mechanism for inheritance of behavioural intervention effects. The benefits of exercise and nutritional interventions in the primary and secondary prevention of CVD are well established, but the mechanisms are not completely understood. In this review, we describe the acute and chronic epigenetic effects of physical activity and dietary changes. We propose exercise and nutrition as potential triggers of epigenetic signals, promoting the reshaping of transcriptional programmes with effects on CVD phenotypes. Finally, we highlight recent developments in epigenetic therapeutics with implications for primary and secondary CVD prevention

Abiotic and biotic sources influencing spring new particle formation in North East Greenland

9 pages, 4 figuresIn order to improve our ability to predict cloud properties, radiative balance and climate, it is crucial to understand the mechanisms that trigger the formation of new particles and their growth to activation sizes. Using an array of real time aerosol measurements, we report a categorization of the aerosol population taken at Villum Research Station, Station Nord (VRS) in North Greenland during a period of 88 days (February–May 2015). A number of New Particle Formation (NPF) events were detected and are herein discussed. Air mass back trajectories analysis plotted over snow-sea ice satellite maps allowed us to correlate early spring (April) NPF events with air masses travelling mainly over snow on land and sea ice, whereas late spring (May) NPF events were associated with air masses that have passed mainly over sea ice regions. Concomitant aerosol mass spectrometry analysis suggests methanesulfonic acid (MSA) and molecular iodine (I) may be involved in the NPF mechanisms. The source of MSA was attributed to open leads within the sea ice. By contrast, iodine was associated with air masses over snow on land and over sea ice, suggesting both abiotic and biotic sources. Measurements of nucleating particle composition as well as gas-phase species are needed to improve our understanding of the links between emissions, aerosols, cloud and climate in the Arctic; therefore our ability to model such processesThe study was supported by the Spanish Ministry of Economy through project BIONUC (CGL 2013-49020-R), PIICE (CTM 2017-89117-R) and the Ramon y Cajal fellowship (RYC-2012-11922). The National Centre for Atmospheric ScienceNCAS Birmingham group is funded by the UK Natural Environment Research Council. [...]. This work was financially supported by the Danish Environmental Protection Agency with means from the MIKA/DANCEA funds for Environmental Support to the Arctic Region, which is part of the Danish contribution to “Arctic Monitoring and Assessment Program” (AMAP) and to the Danish research project “Short lived Climate Forcers” (SLCF), and the Danish Council for Independent Research (project NUMEN, DFF-FTP-4005-00485B). [...] This work was also supported by the Nordic Centre of Excellence (NCoE) Cryosphere-Atmosphere Interactions in a Changing Arctic Climate (CRAICC). The Villum Foundation is acknowledged for funding the construction of Villum Research Station, Station NordPeer Reviewe