Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes.
Pubmed ID: 16537411 RIS Download
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.
Core that offers support for data-driven projects related to basic, clinical and translational research, with a particular emphasis on diabetes. The core aims to ensure that researchers take advantage of the most modern and robust methods available in the field of Bioinformatics and Biostatistics.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on October 27,2023. Core that provides cell sorting and flow cytometry services. Specific services include cell analysis, large object sorting,magnetic cell enrichment, and automatic cell counting.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on October 27,2023. Core that provides services for performing specific morphological procedures, providing training and access to equipment, maintaining the specialized microscopes, and giving advice and interpretation.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on October 27,2023. Core that provides technically advanced physiological evaluation of metabolism in diabetes, obesity, and their associated complications in rodents for DRC investigators and outside users. It also provides training of investigators and trainees in several physiological procedures.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on October 27,2023. Core that provides services for genetic and genomic analysis, including DNA extraction from blood, access to DNA collections from the Core?s repository, SNP genotyping, and support for gene expression studies based on both high-density oligonucleotide arrays and real-time quantitative PCR.
View all literature mentionsCore that maintains a centralized facility for the generation and propagation of reprogrammed iPS cells for use in molecular and cellular pathologies underlying diabetes and its complications.
View all literature mentionsSix component core which facilitates the exchange of research information and discussions among investigators, fellows and students within the Joslin Diabetes Center, as well as between Joslin Staff and outside researchers with similar interests.
View all literature mentions