Diet high in lipid hydroperoxide by vitamin E deficiency induces insulin resistance and impaired insulin secretion in normal rats.
To clarify the effect of dietary lipid hydroperoxide (LPO) on development of glucose intolerance, we fed Sprague-Dawley rats on a diet containing elevated LPO level for 10 weeks and measured both insulin sensitivity and insulin secretion. The contents of LPO in both plasma and skeletal muscle in the LPO-fed rats were significantly higher than those in the controls. Both insulin resistance evaluated by steady-state blood glucose (SSBG) methods and impaired insulin secretion evaluated by oral glucose tolerance test (OGTT) were found in the LPO-fed rats as compared with control rats. Furthermore, the levels of insulin receptor substrate (IRS)-1 protein in the skeletal muscle were significantly lower in the LPO-fed rats. Those impairments were not reversed in LPO-fed rats with supernormal levels of plasma vitamin E following vitamin E supplementation for 5 weeks. Moreover, the immunohistochemical study revealed that NF-kappaB-p50 protein was found in the nucleus of pancreatic beta-cells of the LPO-fed rats, whereas it was not observed in the nucleus of the islets in the control rats. These findings indicate that NF-kappaB is activated in response to oxidative stress in pancreatic islet cells in LPO-fed rats. In conclusion, our studies reveal that diet high in LPO by vitamin E deficiency accelerates glucose intolerance through impairments of both sensitivity and secretion of insulin.
Tsujinaka
Katsumasa
K
The Division of Endocrinology and Metabolism, Department of Medicine, Seta, Otsu, Shiga 520-2192, Japan.
Nakamura
Takaaki
T
Maegawa
Hiroshi
H
Fujimiya
Mineko
M
Nishio
Yoshihiko
Y
Kudo
Motoi
M
Kashiwagi
Atsunori
A
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002467:Cell Nucleus / Q000737:chemistry; D004032:Diet; D018149:Glucose Intolerance / Q000209:etiology; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000503:physiopathology / Q000648:ultrastructure; D008054:Lipid Peroxides / Q000008:administration & dosage* / Q000032:analysis / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D016328:NF-kappa B / Q000032:analysis / Q000502:physiology; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood; D014811:Vitamin E Deficiency / Q000150:complications*
D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D008054:Lipid Peroxides; D016328:NF-kappa B; D010750:Phosphoproteins; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E