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- Keildson, Sarah, et al.
(författare)
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Expression of phosphofructokinase in skeletal muscle is influenced by genetic variation and associated with insulin sensitivity.
- 2014
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:3
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Tidskriftsartikel (refereegranskat)abstract
- Using an integrative approach in which genetic variation, gene expression, and clinical phenotypes are assessed in relevant tissues may help functionally characterize the contribution of genetics to disease susceptibility. We sought to identify genetic variation influencing skeletal muscle gene expression (expression quantitative trait loci [eQTLs]) as well as expression associated with measures of insulin sensitivity. We investigated associations of 3,799,401 genetic variants in expression of >7,000 genes from three cohorts (n = 104). We identified 287 genes with cis-acting eQTLs (false discovery rate [FDR] <5%; P < 1.96 × 10(-5)) and 49 expression-insulin sensitivity phenotype associations (i.e., fasting insulin, homeostasis model assessment-insulin resistance, and BMI) (FDR <5%; P = 1.34 × 10(-4)). One of these associations, fasting insulin/phosphofructokinase (PFKM), overlaps with an eQTL. Furthermore, the expression of PFKM, a rate-limiting enzyme in glycolysis, was nominally associated with glucose uptake in skeletal muscle (P = 0.026; n = 42) and overexpressed (Bonferroni-corrected P = 0.03) in skeletal muscle of patients with T2D (n = 102) compared with normoglycemic controls (n = 87). The PFKM eQTL (rs4547172; P = 7.69 × 10(-6)) was nominally associated with glucose uptake, glucose oxidation rate, intramuscular triglyceride content, and metabolic flexibility (P = 0.016-0.048; n = 178). We explored eQTL results using published data from genome-wide association studies (DIAGRAM and MAGIC), and a proxy for the PFKM eQTL (rs11168327; r(2) = 0.75) was nominally associated with T2D (DIAGRAM P = 2.7 × 10(-3)). Taken together, our analysis highlights PFKM as a potential regulator of skeletal muscle insulin sensitivity.
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| 2. |
- Laven, Daniel, et al.
(författare)
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Lessons Learned from U.S. Experience with Regional Landscape Governance: Implications for Conservation and Protected Areas
- 2015
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Ingår i: Nature Policies and Landscape Policies. - Cham : Springer. - 9783319054100 - 9783319054094 ; , s. 323-330
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Bokkapitel (refereegranskat)abstract
- It is generally acknowledged that protected areas do not encompass the scale necessary for effective conservation of socio-ecological systems. Consequently, there have been repeated calls for a "new paradigm" for conservation that transitions from "islands" to "networks." By extending conservation to reflect wider landscape perspectives, this approach integrates community development and economic and quality of life interests, thereby forging productive relationships between protected areas and their regional context. This broadened agenda involves many more landowners, organizations, and levels of government and requires coordination, partnerships, and new forms of governance. Drawing from nearly a decade of research, this contribution examines US experience with this new paradigm for conservation and models of network governance. The findings from this research program indicate that three key dimensions are fundamental to governance: engaging a diversity of stakeholders and building consensus, creating and sustaining ongoing networks of partners, and developing a central hub for the network. This central coordinating and facilitating function appears to be an essential governance element as it is the activity of these networks of private and public partners that deliver accomplishments. This contribution suggests that despite their challenges, networked-based models can strengthen social capital at regional levels, thereby increasing capacity for innovation, adaptation, and resiliency.
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