Metabolism regulates exposure of pancreatic islets to circulating molecules in vivo.
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Pancreatic beta cells modulate insulin secretion through rapid sensing of blood glucose and integration of gut-derived signals. Increased insulin demand during pregnancy and obesity alters islet function and mass, and leads to gestational and type 2 diabetes in predisposed individuals. However, it is unclear how blood-borne factors dynamically access the islets of Langerhans. Thus, understanding the changes in circulating molecule distribution that accompany compensatory beta cell expansion may be key to developing novel anti-diabetic therapies. Here, using 2-photon microscopy in vivo in mice, we demonstrate that islets are almost instantly exposed to peaks of circulating molecules, which rapidly pervade the tissue before clearance. In addition, both gestation and short-term high fat diet-feeding decrease molecule extravasation and uptake rates in vivo in islets, independently of beta cell expansion or islet blood flow velocity. Together, these data support a role for islet vascular permeability in shaping beta cell adaptive responses to metabolic demand by modulating the access and sensing of circulating molecules.
Date Issued
2015-11-18
Date Acceptance
2015-11-09
Citation
Diabetes, 2015, 65 (2), pp.463-475
ISSN
0012-1797
Publisher
American Diabetes Association
Start Page
463
End Page
475
Journal / Book Title
Diabetes
Volume
65
Issue
2
Copyright Statement
This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online at http://diabetes.diabetesjournals.org.
Sponsor
Diabetes UK
European Foundation for the Study of Diabetes
Identifier
PII: db15-1168
Grant Number
15821
N/A
Subjects
Endocrinology & Metabolism
11 Medical And Health Sciences
Publication Status
Published