title: Improved glucose metabolism in mice lacking alpha-tocopherol transfer protein.
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 (alpha-TTP) mediates the transfer of alpha-tocopherol (alpha-TOH) from hepatocytes to very-low-density lipoproteins, thereby controlling plasma levels of alpha-TOH.
  
  
  OBJECTIVE
  The aim of this study was to investigate the putative impact of alpha-TTP knock-out on glucose metabolism in mice.
  
  
  METHODS
  Mice deficient for alpha-TTP and wild-type control littermates were fed a diet containing 200 mg alpha-tocopheryl acetate per kg to ameliorate alpha-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 alpha-TOH levels of knock-out mice were 34% the levels of wild-type controls: Any signs of alpha-TOH deficiency were absent at any age. Unexpectedly, serum glucose levels both in the fasted and in the fed state were lower in alpha-TTP-deficient mice at any age. Removal rates for intraperitoneally injected glucose were found to be significantly increased in young alpha-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 alpha-TTP-deficient mice.
  
  
  CONCLUSIONS
  Our findings suggest that alpha-TTP-deficiency in states of alpha-TOH supplementation unexpectedly promotes glucose tolerance in mice due to both increased insulin secretion and insulin action, suggesting differential roles of alpha-TTP and alpha-TOH in the pathogenesis of type 2 diabetes mellitus.
authors: Dept. of Human Nutrition, Inst. of Nutrition, University of Jena, Dornburger Strasse 29, 07743, Jena, Germany. marc.birringer@uni-jena.de
authors: Marc
authors: M
authors: Birringer
authors: Doreen
authors: D
authors: Kuhlow
authors: Paul T
authors: PT
authors: Pfluger
authors: Nico
authors: N
authors: Landes
authors: Tim J
authors: TJ
authors: Schulz
authors: Markus
authors: M
authors: Glaubitz
authors: Simone
authors: S
authors: Florian
authors: Andreas
authors: A
authors: Pfeiffer
authors: Markus
authors: M
authors: Schuelke
authors: Regina
authors: R
authors: Brigelius-Flohé
authors: Michael
authors: M
authors: Ristow
mesh_terms: D000367:Age Factors; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000517:prevention & control; D005215:Fasting / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood*; D014811:Vitamin E Deficiency / Q000150:complications; D024502:alpha-Tocopherol / Q000097:blood* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D007328:Insulin; D014280:Triglycerides; C017763:alpha-tocopherol transfer protein; D024502:alpha-Tocopherol; D005947:Glucose