Improved glucose metabolism in mice lacking α-tocopherol transfer protein

Marc Birringer, Doreen Kuhlow, Paul T. Pfluger, Nico Landes, Tim J. Schulz, Markus Glaubitz, Simone Florian, Andreas Pfeiffer, Markus Schuelke, Regina Brigelius-Flohé, Michael Ristow

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish
Pages (from-to)397-405
Number of pages9
JournalEuropean Journal of Nutrition
Issue number7
StatePublished - Oct 2007
Externally publishedYes


  • Alpha tocopherol
  • Alpha-tocopherol transfer protein
  • Diabetes mellitus type 2
  • Glucose metabolism
  • Insulin secretion
  • Insulin sensitivity


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