Searching across hundreds of databases
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Type 2 diabetes is thought to involve a compromised β cell differentiation state, but the mechanisms underlying this dysfunction remain unclear. Here, we report a key role for the TF PAX6 in the maintenance of adult β cell identity and function. PAX6 was downregulated in β cells of diabetic db/db mice and in WT mice treated with an insulin receptor antagonist, revealing metabolic control of expression. Deletion of Pax6 in β cells of adult mice led to lethal hyperglycemia and ketosis that were attributed to loss of β cell function and expansion of α cells. Lineage-tracing, transcriptome, and chromatin analyses showed that PAX6 is a direct activator of β cell genes, thus maintaining mature β cell function and identity. In parallel, we found that PAX6 binds promoters and enhancers to repress alternative islet cell genes including ghrelin, glucagon, and somatostatin. Chromatin analysis and shRNA-mediated gene suppression experiments indicated a similar function of PAX6 in human β cells. We conclude that reduced expression of PAX6 in metabolically stressed β cells may contribute to β cell failure and α cell dysfunction in diabetes.
Pubmed ID: 27941241 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.
Network helps to organize and support collaborative research related to loss of functional beta cell mass in Type 1 Diabetes (T1D). Project consists of four independent research initiatives: Consortium on Beta Cell Death and Survival (CBDS), Consortium on Human Islet Biomimetics (CHIB), Consortium on Modeling Autoimmune Interactions (CMAI), Consortium on Targeting and Regeneration (CTAR), and Human Pancreas Analysis Program (HPAP).
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented May 10, 2017. A pilot effort that has developed a centralized, web-based biospecimen locator that presents biospecimens collected and stored at participating Arizona hospitals and biospecimen banks, which are available for acquisition and use by researchers. Researchers may use this site to browse, search and request biospecimens to use in qualified studies. The development of the ABL was guided by the Arizona Biospecimen Consortium (ABC), a consortium of hospitals and medical centers in the Phoenix area, and is now being piloted by this Consortium under the direction of ABRC. You may browse by type (cells, fluid, molecular, tissue) or disease. Common data elements decided by the ABC Standards Committee, based on data elements on the National Cancer Institute''s (NCI''s) Common Biorepository Model (CBM), are displayed. These describe the minimum set of data elements that the NCI determined were most important for a researcher to see about a biospecimen. The ABL currently does not display information on whether or not clinical data is available to accompany the biospecimens. However, a requester has the ability to solicit clinical data in the request. Once a request is approved, the biospecimen provider will contact the requester to discuss the request (and the requester''s questions) before finalizing the invoice and shipment. The ABL is available to the public to browse. In order to request biospecimens from the ABL, the researcher will be required to submit the requested required information. Upon submission of the information, shipment of the requested biospecimen(s) will be dependent on the scientific and institutional review approval. Account required. Registration is open to everyone., documented on August 1, 2015. Consortium that aims to facilitate interdisciplinary collaborations to advance the understanding of pancreatic islet development and function, with the goal of developing innovative therapies to correct the loss of beta cell mass in diabetes, including cell reprogramming, regeneration and replacement. They are responsible for collaboratively generating the necessary reagents, mouse strains, antibodies, assays, protocols, technologies and validation assays that are beyond the scope of any single research effort. The scientific goals for the BCBC are to: * Use cues from pancreatic development to directly differentiate pancreatic beta cells and islets from stem / progenitor cells for use in cell-replacement therapies for diabetes, * Determine how to stimulate beta cell regeneration in the adult pancreas as a basis for improving beta cell mass in diabetic patients, * Determine how to reprogram progenitor / adult cells into pancreatic beta-cells both in-vitro and in-vivo as a mean for developing cell-replacement therapies for diabetes, and * Investigate the progression of human type-1 diabetes using patient-derived cells and tissues transplanted in humanized mouse models. Many of the BCBC investigator-initiated projects involve reagent-generating activities that will benefit the larger scientific community. The combination of programs and activities should accelerate the pace of major new discoveries and progress within the field of beta cell biology.
View all literature mentions
The NIDDK Information Network (dkNET) serves the needs of basic and clinical investigators by providing seamless access to large pools of data and research resources relevant to the mission of The National Institute of Diabetes Digestive and Kidney Diseases (NIDDK). dkNET is hosted at University of California San Diego, and is supported by NIH NIDDK grant 2U24DK097771-09.
Email: info_at_ dknet.org
