Variance of the SGK1 Gene Is Associated with Insulin Secretion in Different European Populations: Results from the TUEF, EUGENE2, and METSIM Studies

HYPOTHESIS:Serum- and Glucocorticoid-inducible Kinase 1 (SGK1) is involved in the regulation of insulin secretion and may represent a candidate gene for the development of type 2 diabetes mellitus in humans. METHODS:Three independent European populations were analyzed for the association of SGK1 gene (SGK) variations and insulin secretion traits. The German TUEF project provided the screening population (N = 725), and four tagging SNPs (rs1763527, rs1743966, rs1057293, rs9402571) were investigated. EUGENE2 (N = 827) served as a replication cohort for the detected associations. Finally, the detected associations were validated in the METSIM study, providing 3798 non-diabetic and 659 diabetic (type 2) individuals. RESULTS:Carriers of the minor G allele in rs9402571 had significantly higher C-peptide levels in the 2 h OGTT (+10.8%, p = 0.04; dominant model) and higher AUC(C-Peptide)/AUC(Glc) ratios (+7.5%, p = 0.04) compared to homozygous wild type TT carriers in the screening population. As interaction analysis for BMIxrs9402571 was significant (p = 0.04) for the endpoint insulin secretion, we stratified the TUEF cohort for BMI, using a cut off point of BMI = 25. The effect on insulin secretion only remained significant in lean TUEF participants (BMI< or =25). This finding was replicated in lean EUGENE2 rs9402571 minor allele carriers, who had a significantly higher AUC(Ins)/AUC(Glc) (TT: 226+/-7, XG: 246+/-9; p = 0.019). Accordingly, the METSIM trial revealed a lower prevalence of type 2 diabetes (OR: 0.85; 95%CI: 0.71-1.01; p = 0.065, dominant model) in rs9402571 minor allele carriers. CONCLUSIONS:The rs9402571 SGK genotype associates with increased insulin secretion in lean non-diabetic TUEF/EUGENE2 participants and with lower diabetes prevalence in METSIM. Our study in three independent European populations supports the conclusion that SGK variability affects diabetes risk

Understanding environmental change through the lens of trait-based, functional, and phylogenetic biodiversity in freshwater ecosystems

Abstract In the era of the Anthropocene, environmental change is accelerating biodiversity loss across ecosystems on Earth, among which freshwaters are likely the most threatened. Different biodiversity facets in the freshwater realm suffer from various environmental changes that jeopardize the ecosystem functions and services important for humankind. In this work we examine how environmental changes (e.g., climate change, eutrophication, or invasive species) affect trait-based, functional, and phylogenetic diversity of biological communities. We first developed a simple conceptual model of the possible relationships between environmental change and these three diversity facets in freshwaters and, secondly, systematically reviewed articles where these relationships had been investigated in different freshwater ecosystems. Finally, we highlighted research gaps from the perspectives of organisms, ecosystems, stressors, and geographical locations. Our conceptual model suggested that both natural factors and global change operating at various spatial scales influence freshwater community structure and ecosystem functioning. The relationships between biodiversity and environmental change depend on geographical region, organism group, spatial scale, and environmental change gradient length. The systematic review revealed that environmental change impacts biodiversity patterns in freshwaters, but there is no single type of biodiversity response to the observed global changes. Natural stressors had different, even contradictory, effects (i.e., multiple, negative, and positive) on biodiversity compared with anthropogenic stressors. Anthropogenic stressors more often decreased biodiversity, although eutrophication and climate change affected freshwater ecosystems in a complex, more multi-dimensional way. The research gaps we identified were related, for example, to the low number of community-based biodiversity studies, the lack of information on true phylogenies for all freshwater organism groups, the missing evaluations whether species traits are phylogenetically conserved, and the geographical biases in research (i.e., absence of studies from Africa, Southern Asia, and Russia). We hope that our review will stimulate more research on the less well-known facets and topics of biodiversity loss in highly vulnerable freshwater ecosystems