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.
A better understanding of processes controlling the development and function of pancreatic islets is critical for diabetes prevention and treatment. Here, we reveal a previously unappreciated function for pancreatic β2-adrenergic receptors (Adrb2) in controlling glucose homeostasis by restricting islet vascular growth during development. Pancreas-specific deletion of Adrb2 results in glucose intolerance and impaired insulin secretion in mice, and unexpectedly, specifically in females. The metabolic phenotypes were recapitulated by Adrb2 deletion from neonatal, but not adult, β-cells. Mechanistically, Adrb2 loss increases production of Vascular Endothelial Growth Factor-A (VEGF-A) in female neonatal β-cells and results in hyper-vascularized islets during development, which in turn, disrupts insulin production and exocytosis. Neonatal correction of islet hyper-vascularization, via VEGF-A receptor blockade, fully rescues functional deficits in glucose homeostasis in adult mutant mice. These findings uncover a regulatory pathway that functions in a sex-specific manner to control glucose metabolism by restraining excessive vascular growth during islet development.
Pubmed ID: 30303066
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.
Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsAllen Mouse Brain Atlas includes full color, high resolution anatomic reference atlas accompanied by systematic, hierarchically organized taxonomy of mouse brain structures. Enables interactive online exploration of atlas and to provide deeper level of 3D annotation for informatics analysis and viewing in Brain Explorer 3D viewer.
View all literature mentionsThis polyclonal targets Mouse VEGF R2 / KDR / Flk-1
View all literature mentionsThis polyclonal targets LAMA5
View all literature mentionsThis unknown targets Neuropeptide Y
View all literature mentionsThis monoclonal targets Glucagon antibody [K79bB10]
View all literature mentionsThis polyclonal targets Collagen IV antibody
View all literature mentionsThis polyclonal targets Porcine pancreatic insulin
View all literature mentionsThis unknown targets Glucose Transporter 2 (Glut-2)
View all literature mentionsMus musculus with name B6.FVB-Tg(Ipf1-cre)1Tuv/Nci from IMSR.
View all literature mentionsMus musculus with name B6.FVB-Tg(Ipf1-cre)1Tuv/Nci from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Ins1-EGFP)1Hara/J from IMSR.
View all literature mentionsMus musculus with name STOCK Tg(Pdx1-cre/Esr1*)#Dam/J from IMSR.
View all literature mentionsThis polyclonal targets Mouse VEGF R2 / KDR / Flk-1
View all literature mentionsThis polyclonal targets LAMA5
View all literature mentionsMus musculus with name STOCK Tg(Pdx1-cre/Esr1*)#Dam/J from IMSR.
View all literature mentionsThis unknown targets Neuropeptide Y
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Ins1-EGFP)1Hara/J from IMSR.
View all literature mentionsThis polyclonal targets Collagen IV antibody
View all literature mentionsThis monoclonal targets Glucagon antibody [K79bB10]
View all literature mentionsThis polyclonal targets Porcine pancreatic insulin
View all literature mentionsThis unknown targets Glucose Transporter 2 (Glut-2)
View all literature mentions