Pancreatic insulin release in vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice

Takafumi Senmaru, Masahiro Yamazaki, Hiroshi Okada, Mai Asano, Michiaki Fukui, Naoto Nakamura, Hiroshi Obayashi, Yoshitaka Kondo, Naoki Maruyama, Akihito Ishigami, Goji Hasegawa

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 intra- peritoneal 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.

Original languageEnglish
Pages (from-to)114-118
Number of pages5
JournalJournal of Clinical Biochemistry and Nutrition
Volume50
Issue number2
DOIs
Publication statusPublished - 2012 Mar
Externally publishedYes

Keywords

  • Gluconolactonase
  • Insulin
  • Islet
  • Senescence marker protein-30
  • Vitamin C

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Clinical Biochemistry

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    Senmaru, T., Yamazaki, M., Okada, H., Asano, M., Fukui, M., Nakamura, N., Obayashi, H., Kondo, Y., Maruyama, N., Ishigami, A., & Hasegawa, G. (2012). Pancreatic insulin release in vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice. Journal of Clinical Biochemistry and Nutrition, 50(2), 114-118. https://doi.org/10.3164/jcbn.11-52