Pdx1 restores β cell function in Irs2 knockout mice

The homeodomain transcription factor Pdx1 is required for pancreas development, including the differentiation and function of β cells. Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic β cell growth and function. To investigate whether β cell failure in Irs2(–/–) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(–/–) mice. Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(–/–) mice, whereas it was expressed normally in islets from wild-type or Irs1(–/–) mice, which do not develop diabetes. Whereas male Irs2(–/–)Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(–/–) mice. By contrast, transgenic expression of Pdx1 restored β cell mass and function in Irs2(–/–) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY

Patterns and determinants of shorebird species richness in the circumpolar Arctic

Aim The intention with this study was first to investigate and describe the broad-scale geographical patterns of species richness of breeding shorebirds (Charadriiformes; families: Charadriidae, Scolopacidae and Haematopodidae) throughout the arctic tundra biome. Secondly, after compensating for the positive relationship between net primary productivity (NPP) and species richness, the relative importance of additional ecological and historical variables for species richness was investigated. The main variables considered are NPP, length of snow- and ice-free season, accessibility of regions depending on migratory flyway systems, tundra area at Pleistocene (120 and 20-18 ka bp) and Holocene (8 ka bp) times, and tundra area at present. Methods Information on shorebird species breeding distributions was compiled from distribution atlases and species accounts. The breeding distributions of shorebirds with ranges partly or completely in the Arctic (a total of 50 species) were mapped in ArcView 3.2 to create a raster grid layer of shorebird species richness at a 1degrees latitude x longitude resolution. The total and mean species richness value was calculated per each 10degrees of longitude sector of the Arctic. The relationships between species richness and the different climatic and environmental variables were analysed on the basis of this sector-wise division of the arctic tundra. The influence of each variable on species richness was investigated using univariate and multivariate analyses (multivariate linear regression and general linear model). Results We found that patterns of breeding shorebird species richness in the Arctic tundra biome are to a large degree determined by the NPP, the length of the snow- or ice-free season, the diversity of migratory flyways, as well as the historical extent of tundra habitat area during the maximum cooling of the last glacial period. Essentially, two main regions are distinguishable in the circumpolar Arctic regarding shorebird community richness. These are a species-rich Beringia-centred region and a species-poor Atlantic-centred region. Main conclusions The underlying explanations to these major trends may primarily be attributed to factors that operate at present through accessibility of areas from contemporary migration flyways, as well as processes that operated in the past during and after the last glacial cycle. The most prominent influence on the shorebird diversity was found for NPP in combination with the diversity of migratory flyways. These flyways provide the links between breeding and wintering resources, often separated by huge distances, and the geographical and ecological conditions associated with the shorebirds' migration seem to be of particular importance for their breeding diversity in different sectors of circumpolar tundra