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

Senmaru T, Yamazaki M, Okada H, Asano M, Fukui M, Nakamura N, Obayashi H, Kondo Y, Maruyama N, Ishigami A, Hasegawa G - J Clin Biochem Nutr (2011)

Bottom Line: We recently identified senescence marker protein-30 as the lactone-hydrolyzing enzyme gluconolactonase, which is involved in vitamin C biosynthesis.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Blood glucose levels in the intraperitoneal glucose tolerance test at 15 weeks of age. ● VC (+) SMP30/GNL knockout (KO), ◯ VC (−) SMP30/GNL knockout (KO), ▲ VC (+) wild type (WT), △ VC (−) wild type (WT). *p<0.01 VC (−) KO vs VC (−) WT and VC (+) WT. VC: vitamin C, VC (+): free access to water containing 1.5 g/L VC for 8 weeks from 7 weeks of age, VC (−): free access to water containing 37.5 mg/L VC for 8 weeks from 7 weeks of age, AUC: area under curve. #p<0.05 VC (−) KO vs VC (−) WT and VC (+) WT. Data are means ± SE (n = 7).
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Figure 1: Blood glucose levels in the intraperitoneal glucose tolerance test at 15 weeks of age. ● VC (+) SMP30/GNL knockout (KO), ◯ VC (−) SMP30/GNL knockout (KO), ▲ VC (+) wild type (WT), △ VC (−) wild type (WT). *p<0.01 VC (−) KO vs VC (−) WT and VC (+) WT. VC: vitamin C, VC (+): free access to water containing 1.5 g/L VC for 8 weeks from 7 weeks of age, VC (−): free access to water containing 37.5 mg/L VC for 8 weeks from 7 weeks of age, AUC: area under curve. #p<0.05 VC (−) KO vs VC (−) WT and VC (+) WT. Data are means ± SE (n = 7).

Mentions: Blood glucose levels 30 min after glucose administration were significantly higher in VC (+) SMP30/GNL KO mice than in VC (−) or VC (+) WT mice (p<0.05, Fig. 1). In addition, blood glucose levels in VC (−) SMP30/GNL KO mice 30, 60, and 120 min after glucose administration were significantly higher than those of WT mice in either group (p<0.01, Fig. 1). However, there were no significant differences in blood glucose levels between VC (−) and VC (+) SMP30/GNL KO mice at any time point. VC supplementation did not affect glucose tolerance in WT mice. A significant increase in area under the curve (AUC, 0–120 min) was detected only in VC (−) SMP30/GNL KO mice when compared to VC (−) and VC (+) WT mice (p<0.01, Fig. 1). No significant difference in AUC was detected between VC (−) and VC (+) SMP30/GNL KO mice.


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

Senmaru T, Yamazaki M, Okada H, Asano M, Fukui M, Nakamura N, Obayashi H, Kondo Y, Maruyama N, Ishigami A, Hasegawa G - J Clin Biochem Nutr (2011)

Blood glucose levels in the intraperitoneal glucose tolerance test at 15 weeks of age. ● VC (+) SMP30/GNL knockout (KO), ◯ VC (−) SMP30/GNL knockout (KO), ▲ VC (+) wild type (WT), △ VC (−) wild type (WT). *p<0.01 VC (−) KO vs VC (−) WT and VC (+) WT. VC: vitamin C, VC (+): free access to water containing 1.5 g/L VC for 8 weeks from 7 weeks of age, VC (−): free access to water containing 37.5 mg/L VC for 8 weeks from 7 weeks of age, AUC: area under curve. #p<0.05 VC (−) KO vs VC (−) WT and VC (+) WT. Data are means ± SE (n = 7).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3303473&req=5

Figure 1: Blood glucose levels in the intraperitoneal glucose tolerance test at 15 weeks of age. ● VC (+) SMP30/GNL knockout (KO), ◯ VC (−) SMP30/GNL knockout (KO), ▲ VC (+) wild type (WT), △ VC (−) wild type (WT). *p<0.01 VC (−) KO vs VC (−) WT and VC (+) WT. VC: vitamin C, VC (+): free access to water containing 1.5 g/L VC for 8 weeks from 7 weeks of age, VC (−): free access to water containing 37.5 mg/L VC for 8 weeks from 7 weeks of age, AUC: area under curve. #p<0.05 VC (−) KO vs VC (−) WT and VC (+) WT. Data are means ± SE (n = 7).
Mentions: Blood glucose levels 30 min after glucose administration were significantly higher in VC (+) SMP30/GNL KO mice than in VC (−) or VC (+) WT mice (p<0.05, Fig. 1). In addition, blood glucose levels in VC (−) SMP30/GNL KO mice 30, 60, and 120 min after glucose administration were significantly higher than those of WT mice in either group (p<0.01, Fig. 1). However, there were no significant differences in blood glucose levels between VC (−) and VC (+) SMP30/GNL KO mice at any time point. VC supplementation did not affect glucose tolerance in WT mice. A significant increase in area under the curve (AUC, 0–120 min) was detected only in VC (−) SMP30/GNL KO mice when compared to VC (−) and VC (+) WT mice (p<0.01, Fig. 1). No significant difference in AUC was detected between VC (−) and VC (+) SMP30/GNL KO mice.

Bottom Line: We recently identified senescence marker protein-30 as the lactone-hydrolyzing enzyme gluconolactonase, which is involved in vitamin C biosynthesis.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus