Serum selenoprotein P, but not selenium, predicts future hyperglycemia in a general Japanese population

Abstract

We aimed to test the hypothesis that selenoprotein P (SELENOP), a hepatokine involved in the development of both insulin resistance and impaired insulin production in mice, is related to future onset of hyperglycemia in humans. 76 healthy non-pregnant human subjects without diabetes underwent oral glucose tolerance test (OGTT) at baseline and 4-years follow-up. Nine subjects developed either impaired glucose tolerance or type 2 diabetes at follow-up. At baseline, SELENOP concentrations correlated negatively with insulinogenic index, but not with homeostasis model assessment-estimated insulin resistance (HOMA-IR). Multivariate analysis showed that baseline SELENOP predicted fasting plasma glucose at follow-up independently of the other parameters. The receiver operating characteristic (ROC) curve analysis showed that baseline concentrations of serum SELENOP, but not of selenium, were a reliable test to predict future onset of glucose intolerance. In conclusion, elevation of circulating SELENOP, but not of circulating selenium, was positively and independently associated with future onset of glucose intolerance in a general Japanese population.

Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity

“…In a general Japanese population plasma Se levels were directly associated with waist circumference (r = 0.329; p = 0.029) but not BMI (r = 0.225; p = 0.187), whereas circulating SELENOP levels were unrelated to anthropometric parameters [61].…”

Selenoprotein P as an <i>in vivo</i> redox regulator: disorders related to its deficiency and excess

“…(53)(54)(55) However, recent evidence shows an increase of SeP in type 2 diabetes patients, and excess SeP levels have undesirable effects on the glucose metabolism. (17)(18)(19)46,(56)(57)(58) This indicates that increased SeP levels are a significant therapeutic target for this lifestylerelated disease. The increase of SeP in diabetic patients has been discovered by comprehensive gene expression analysis of mRNA samples obtained from liver biopsies of diabetic patients.…”

“…(17) A significantly positive correlation between SeP expression levels and biomarkers of diabetes, such as fasting glucose and blood glucose levels after administrations of a glucose tolerance test, has been shown. (17,(57)(58)(59)(60) To increase SeP levels, enough Se intake is necessary; however, this might not be sufficient. Normal mice chow contains 0.4 mg Se/kg, which causes neither an increase in SeP levels nor high blood glucose levels in normal mice.…”

“…The rearrangement and decrease of both a-and b-cells has been observed in the animal diabetes model and in humans. (73)(74)(75) Recently, it has been shown that SeP levels are negatively correlated with the insulinogenic index, an indicator of insulin secretion, (57) suggesting that excess SeP is a considerable therapeutic target to protect pancreas function in patients with type 2 diabetes.…”

Alcohol Intake Is Associated With Elevated Serum Levels of Selenium and Selenoprotein P in Humans

“…Selenoprotein P eliminates a physiologic burst of reactive oxygen species required for intracellular signal transduction, a condition referred to as “reductive stress” ( 2 ). Serum levels of selenoprotein P are elevated during aging ( 8 ), and in people with type 2 diabetes ( 3 ), non-alcoholic fatty liver disease ( 9 ), and chronic hepatitis C ( 10 ).…”