Metabolic Network Topology Reveals Transcriptional Regulatory Signatures of Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is a disorder characterized by both insulin resistance and impaired insulin secretion. Recent transcriptomics studies related to T2DM have revealed changes in expression of a large number of metabolic genes in a variety of tissues. Identification of the molecular mechanisms underlying these transcriptional changes and their impact on the cellular metabolic phenotype is a challenging task due to the complexity of transcriptional regulation and the highly interconnected nature of the metabolic network. In this study we integrate skeletal muscle gene expression datasets with human metabolic network reconstructions to identify key metabolic regulatory features of T2DM. These features include reporter metabolites—metabolites with significant collective transcriptional response in the associated enzyme-coding genes, and transcription factors with significant enrichment of binding sites in the promoter regions of these genes. In addition to metabolites from TCA cycle, oxidative phosphorylation, and lipid metabolism (known to be associated with T2DM), we identified several reporter metabolites representing novel biomarker candidates. For example, the highly connected metabolites NAD+/NADH and ATP/ADP were also identified as reporter metabolites that are potentially contributing to the widespread gene expression changes observed in T2DM. An algorithm based on the analysis of the promoter regions of the genes associated with reporter metabolites revealed a transcription factor regulatory network connecting several parts of metabolism. The identified transcription factors include members of the CREB, NRF1 and PPAR family, among others, and represent regulatory targets for further experimental analysis. Overall, our results provide a holistic picture of key metabolic and regulatory nodes potentially involved in the pathogenesis of T2DM

Rabbit and hare management in Washington State home yards and gardens

We often think of rabbits as cute, furry, and harmless, but some species can cause extensive damage to home gardens and orchards throughout the year. Here you will learn how to protect your plants and still enjoy having wild rabbits and hares in your yard

Mole management in Washington backyards

Moles are serious pests to lawns and gardens in western Washington, along with a few areas east of the Cascade Mountains. This publication will help home gardeners develop a multi-action plan to deal with moles in the home landscape

Pests: Vole management in home backyards and gardens

Our native PNW voles undergo periodic population explosions during which time they cause extensive damage within their home ranges. This fact sheet will help identify voles and the damage they cause and suggest management options

What is Tunneling in My Yard?

This publication will help homeowners identify vertebrate pests that tunnel in lawn and garden areas around the home. Successful pest management depends upon being able to identify signs of infestation and identify the pests, before moving on to management options

Washington bumble bees in home yards and gardens

Bumble bees, with their robust bodies, colorful bands of “fur” and audible “buzz” while in flight are the most well recognized of the native bees in Washington State. Equipped with pollen collecting hairy bodies and “pollen baskets” on their hind legs for transport, plus the ability to “buzz pollinate” flowers when necessary, bumble bees are effective pollinators of many crops, home garden plants, ornamentals, and native plants. Some researchers are concerned that bumble bee diversity and abundance in North America are in decline. WSU Extension is hopeful that public awareness and appreciation of bumble bees and their role in pollination will encourage homeowners to better conserve and protect bumble bees in home landscapes here in the Pacific Northwest. This publication will help readers recognize bumble bees, understand their general life cycle, and suggest things homeowners and the general public can do to encourage these fascinating and beneficial insects

West Nile Virus : protect your horses from West Nile Virus

West Nile Virus (WNV) is one of the most important mosquito-vectored diseases of horses in North America and worldwide (Chancy et al. 2015). There are a number of other biting insects that attack horses, but only a few species of mosquitoes are efficient vectors of this serious disease. According to the American Association of Equine Practitioners (AAEP), more than 25,000 cases of equine encephalitis can be attributed to WNV since it was first detected in the United States in 1999. Risk of sickness and death from WNV and other mosquito-borne equine encephalitis viruses are greatly reduced by proper vaccination and mosquito control efforts

Common spiders of Washington

Wherever you find insects, you are likely to find spiders lurking nearby. All spiders are predators that have coevolved with their prey—primarily insects and other arthropods. Spiders have evolved numerous and fascinating strategies to trap, stalk, ambush, or hunt live insects. All spiders possess mouthparts, in the form of fangs, to subdue their prey. Thus, all spiders can bite, and some of them are large enough to bite humans and pets, but only in self-defense. Here in the Pacific Northwest, only one species of spider has been documented as venomous to humans. The objective of this publication is to help residents, gardeners, and naturalists recognize the most common spiders found in Washington State and appreciate them as beneficial organisms. This publication also seeks to reduce human exposure to the nuisance of, and bites from, spiders

Common spiders of Washington

Wherever you find insects, you are likely to find spiders lurking nearby. All spiders are predators that have coevolved with their prey—primarily insects and other arthropods. Spiders have evolved numerous and fascinating strategies to trap, stalk, ambush, or hunt live insects. All spiders possess mouthparts, in the form of fangs, to subdue their prey. Thus, all spiders can bite, and some of them are large enough to bite humans and pets, but only in self-defense. Here in the Pacific Northwest, only one species of spider has been documented as venomous to humans. The objective of this publication is to help residents, gardeners, and naturalists recognize the most common spiders found in Washington State and appreciate them as beneficial organisms. This publication also seeks to reduce human exposure to the nuisance of, and bites from, spiders

Integrin α1-null mice exhibit improved fatty liver when fed a high fat diet despite severe hepatic insulin resistance

Hepatic insulin resistance is associated with increased collagen. Integrin α1β1 is a collagen-binding receptor expressed on hepatocytes. Here, we show that expression of the α1 subunit is increased in hepatocytes isolated from high fat (HF)-fed mice. To determine whether the integrin α1 subunit protects against impairments in hepatic glucose metabolism, we analyzed glucose tolerance and insulin sensitivity in HF-fed integrin α1-null (itga1(−/−)) and wild-type (itga1(+/+)) littermates. Using the insulin clamp, we found that insulin-stimulated hepatic glucose production was suppressed by ∼50% in HF-fed itga1(+/+) mice. In contrast, it was not suppressed in HF-fed itga1(−/−) mice, indicating severe hepatic insulin resistance. This was associated with decreased hepatic insulin signaling in HF-fed itga1(−/−) mice. Interestingly, hepatic triglyceride and diglyceride contents were normalized to chow-fed levels in HF-fed itga1(−/−) mice. This indicates that hepatic steatosis is dissociated from insulin resistance in HF-fed itga1(−/−) mice. The decrease in hepatic lipid accumulation in HF-fed itga1(−/−) mice was associated with altered free fatty acid metabolism. These studies establish a role for integrin signaling in facilitating hepatic insulin action while promoting lipid accumulation in mice challenged with a HF diet