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. AIM OF THE STUDY: 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.
BACKGROUND: Conflicting evidence suggests a possible role for vitamin E in mammalianglucose 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. AIM OF THE STUDY: 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: Y Terasawa; Z Ladha; S W Leonard; J D Morrow; D Newland; D Sanan; L Packer; M G Traber; R V Farese Journal: Proc Natl Acad Sci U S A Date: 2000-12-05 Impact factor: 11.205
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