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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 diabetes mellitus 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 antidiabetic therapies. Here, using two-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.

Original publication

DOI

10.2337/db15-1168

Type

Journal article

Journal

Diabetes

Publication Date

2016

Volume

65

Pages

463 - 475

Keywords

Animals Blood Flow Velocity *Capillary Permeability Cell Proliferation Diabetes Mellitus, Type 2/metabolism Diabetes, Gestational/metabolism Diet, High-Fat/adverse effects Female Insulin/*metabolism Insulin-Secreting Cells/cytology/metabolism/*physiology Intravital Microscopy Mice Microscopy, Fluorescence, Multiphoton Pancreas/blood supply Pregnancy