title: Normal islet vascularization is dispensable for expansion of beta-cell mass in response to high-fat diet induced insulin resistance.
abstract: The inability to increase of islet mass adequately to compensate for the demand of insulin due to insulin resistance is an important pathophysiological feature of type 2 diabetes. Previous studies suggested a relationship between pancreatic beta-cell mass and islet vascularization, although no evidence has confirmed this association in response to insulin resistance. Vascular endothelial growth factor-A (VEGF-A) in islets is essential for maintaining normal islet blood vessels. Here, insulin resistance was induced in mice carrying a beta-cell-specific VEGF-A gene mutation (RIP-Cre:Vegf(fl/fl)) by 20-week feeding of high-fat diet as a model of impaired islet vascularization. These mice showed only a modest decrease in glucose tolerance, compared with control mice. In addition, although the endothelial cell area in the islets of high-fat-fed RIP-Cre:Vegf(fl/fl) mice remained diminished, the pancreatic beta-cell area was modestly more than in high-fat-fed control mice. Thus, normal islet vascularization does not seem to be essential for expansion of beta cell mass in response to insulin resistance.
authors.affiliation: Department of Medicine, Metabolism and Endocrinology, Juntendo University, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Toyofuku
authors.forename: Toyoyoshi
authors.initials: T
authors.lastname: Uchida
authors.forename: Shiho
authors.initials: S
authors.lastname: Nakayama
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hirose
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada