title: Pancreatic insulin release in vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice.
abstract: We recently identified senescence marker protein-30 as the lactone-hydrolyzing enzyme gluconolactonase, which is involved in vitamin C biosynthesis. In this study, we investigated the effects of vitamin C on insulin secretion from pancreatic β-cells using senescence marker protein-30/gluconolactonase knockout mice. In intraperitoneal glucose tolerance tests, vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice demonstrated impaired glucose tolerance with significantly lower blood insulin levels at 30 and 120 min post-challenge than in wild type mice (p<0.01-0.05). In contrast, vitamin C-sufficient senescence marker protein-30/gluconolactonase knockout mice demonstrated significantly higher blood glucose and lower insulin only at the 30 min post-challenge time point (p<0.05). Senescence marker protein-30/gluconolactonase knockout mice showed enhanced insulin sensitivity regardless of vitamin C status. Static incubation of islets revealed that 20 mM glucose-stimulated insulin secretion and islet ATP production were significantly decreased at 60 min only in vitamin C-deficient SMP30/GNL knockout mice relative to wild type mice (p<0.05). These results indicate that the site of vitamin C action lies between glycolysis and mitochondrial oxidative phosphorylation, while SMP30 deficiency itself impairs the distal portion of insulin secretion pathway.
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Hirokoji, Kamikyo-ku, Kyoto 602-8556, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Senmaru
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okada
authors.forename: Mai
authors.initials: M
authors.lastname: Asano
authors.forename: Michiaki
authors.initials: M
authors.lastname: Fukui
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Obayashi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kondo
authors.forename: Naoki
authors.initials: N
authors.lastname: Maruyama
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.forename: Goji
authors.initials: G
authors.lastname: Hasegawa