Adrb2 controls glucose homeostasis by developmental regulation of pancreatic islet vasculature.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Ceasrine, AM; Lin, EE; Lumelsky, DN; Iyer, R; Kuruvilla, R

Published Date

  • October 10, 2018

Published In

Volume / Issue

  • 7 /

PubMed ID

  • 30303066

Pubmed Central ID

  • PMC6200393

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

International Standard Serial Number (ISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/elife.39689

Language

  • eng