Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Skeletal muscle constitutes the major site of glucose uptake leading to increased removal of glucose from the circulation in response to insulin. Type 2 diabetes and obesity are often associated with insulin resistance that can be counteracted by exercise or the use of drugs increasing the relative proportion of oxidative fibers. RIP140 is a transcriptional coregulator with a central role in metabolic tissues and we tested the effect of modulating its level of expression on muscle glucose and lipid metabolism in two mice models. Here, we show that although RIP140 protein is expressed at the same level in both oxidative and glycolytic muscles, it inhibits both fatty acid and glucose utilization in a fiber-type dependent manner. In RIP140-null mice, fatty acid utilization increases in the extensor digitorum longus and this is associated with elevated expression of genes implicated in fatty acid binding and transport. In the RIP140-null soleus, depletion of RIP140 leads to increased GLUT4 trafficking and glucose uptake with no change in Akt activity. AMPK phosphorylation/activity is inhibited in the soleus of RIP140 transgenic mice and increased in RIP140-null soleus. This is associated with increased UCP1 expression and mitochondrial uncoupling revealing the existence of a signaling pathway controlling insulin-independent glucose uptake in the soleus of RIP140-null mice. In conclusion, our findings reinforce the participation of RIP140 in the maintenance of energy homeostasis by acting as an inhibitor of energy production and particularly point to RIP140 as a promising therapeutic target in the treatment of insulin resistance.
Pubmed ID: 22389706
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
The Wellcome Trust is the largest charity in the UK. We fund innovative biomedical research, in the UK and internationally, spending over 600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust is an independent charity funding research to improve human and animal health. Established in 1936 and with an endowment of around 13 billion, it is the UK's largest non-governmental source of funds for biomedical research. What we do We spend over 600 million every year both in the UK and internationally achieving our mission. Funding We support many different kinds of research and activities with the ultimate aim of protecting and improving human and animal health. This support is not restricted to UK researchers - we devote significant funding to international research too. Biomedical science Our biomedical science funding enables the investigation of health and disease in humans and animals. This includes funding for scientists, clinicians and veterinarians at different career stages. Technology transfer Our technology transfer funding supports the development of innovative, early-stage projects with potential medical applications. Medical humanities Our medical humanities funding supports research into biomedical ethics and the history of medicine. Public engagement Our public engagement funding promotes interest, excitement and debate around science and society. Capital funding Our capital funding is for large-scale construction or refurbishment projects in the UK that support science, public engagement, medical history, or the activities of learned societies. Strategic awards Our Strategic Awards provide flexible funding that adds value to excellent research groups. Managing a grant This area contains information and resources to help you manage a grant once it has been awarded, from the grant-start certificate to the end-of-grant report and beyond. Education Resources Teaching and education Resources to help promote contemporary science in the curriculum and to enable young people to engage with biomedical science. Tree of Life Darwin200 Big Picture Science Learning Centres Scientific animations Creative Encounters Courses and conferences Trust-run conferences, courses and workshops for scientists, historians, ethicists, social scientists, teachers, healthcare professionals and policymakers, held in the UK and overseas. Advanced Courses Scientific conferences Conference centres Retreats History of medicine Biomedical ethics Biomedical resources Tools, databases and information to support different areas of biomedical research, including genomics, post-genomics and developmental biology. Animal research Genomics Model organisms Microorganisms Post-genomics Tissues Researcher support Support and advice for all kinds of engagement activities to help you communicate your work in the most effective and rewarding way possible. About researcher support National opportunities Regional opportunities Highlights Publications Browse a wealth of publications covering all aspects of the work we fund. Wellcome Trust websites Explore a range of sites covering key biomedical topics and our public engagement activities.
View all literature mentionsCommercial antibody vendor which supplies antibodies and other products to life science researchers.
View all literature mentionsCell line C2C12 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentions