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Improved glucose metabolism in mice lacking α-tocopherol transfer protein

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Abstract

Background

Conflicting evidence suggests a possible role for vitamin E in mammalian glucose metabolism and the protection from type 2 diabetes. The alpha-tocopherol transfer protein (α-TTP) mediates the transfer of α-tocopherol (α-TOH) from hepatocytes to very-low-density lipoproteins, thereby controlling plasma levels of α-TOH.

Aim of the study

The aim of this study was to investigate the putative impact of α-TTP knock-out on glucose metabolism in mice.

Methods

Mice deficient for α-TTP and wild-type control littermates were fed a diet containing 200 mg α-tocopheryl acetate per kg to ameliorate α-TOH deficiency in knock-out mice. We investigated fasting and postprandial plasma glucose, insulin and triglyceride levels of both groups of mice at different ages. All genotypes and age groups were further subjected to glucose and insulin tolerance tests, and number of insulin-producing islets of Langerhans were determined.

Results

Plasma α-TOH levels of knock-out mice were 34% the levels of wild-type controls: Any signs of α-TOH deficiency were absent at any age. Unexpectedly, serum glucose levels both in the fasted and in the fed state were lower in α-TTP-deficient mice at any age. Removal rates for intraperitoneally injected glucose were found to be significantly increased in young α-TTP-deficient mice. This improved glucose tolerance was caused by increased insulin secretion in response to an intraperitoneal glucose challenge due to an increased number of pancreatic islets, as well as by increased sensitivity to intraperitoneally injected insulin, both significantly promoting glucose metabolism in α-TTP-deficient mice.

Conclusions

Our findings suggest that α-TTP-deficiency in states of α-TOH supplementation unexpectedly promotes glucose tolerance in mice due to both increased insulin secretion and insulin action, suggesting differential roles of α-TTP and α-TOH in the pathogenesis of type 2 diabetes mellitus.

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Acknowledgments

The authors wish to thank Dr. Robert V. Farese for generously providing α-TTP knock-out mice. The excellent technical assistance of Susann Richter and Elke Thom is gratefully acknowledged. This study was supported by a grant of the Deutsche Forschungsgemeinschaft and the Wilhelm-Sander-Stiftung (both to M.R.).

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Authors and Affiliations

  1. Dept. of Human Nutrition, Inst. of Nutrition, University of Jena, Dornburger Straße 29, 07743, Jena, Germany

    Marc Birringer, Doreen Kuhlow, Tim J. Schulz & Michael Ristow

  2. Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany

    Doreen Kuhlow, Tim J. Schulz, Markus Glaubitz, Simone Florian, Andreas Pfeiffer & Michael Ristow

  3. Biochemistry of Micronutrients, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany

    Paul T. Pfluger, Nico Landes & Regina Brigelius-Flohé

  4. Charité University Medicine, Berlin, Germany

    Andreas Pfeiffer & Markus Schuelke

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  1. Marc Birringer
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Correspondence to Marc Birringer.

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Marc Birringer and Doreen Kuhlow have contributed equally to this publication.

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Birringer, M., Kuhlow, D., Pfluger, P.T. et al. Improved glucose metabolism in mice lacking α-tocopherol transfer protein. Eur J Nutr 46, 397–405 (2007). https://doi.org/10.1007/s00394-007-0679-2

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  • DOI: https://doi.org/10.1007/s00394-007-0679-2

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