Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice.
There are conflicting reports on the link between the micronutrient selenium and the prevalence of diabetes. To investigate the possibility that selenium acts as a "double-edged sword" in diabetes, cDNA microarray profiling and two-dimensional differential gel electrophoresis coupled with...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4077766?pdf=render |
id |
doaj-8535e4da3019490aa2c7f1380e55abf7 |
---|---|
record_format |
Article |
spelling |
doaj-8535e4da3019490aa2c7f1380e55abf72020-11-25T02:22:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10131510.1371/journal.pone.0101315Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice.Chaoqun WangShulin YangNingbo ZhangYulian MuHongyan RenYefu WangKui LiThere are conflicting reports on the link between the micronutrient selenium and the prevalence of diabetes. To investigate the possibility that selenium acts as a "double-edged sword" in diabetes, cDNA microarray profiling and two-dimensional differential gel electrophoresis coupled with mass spectrometry were used to determine changes in mRNA and protein expression in pancreatic and liver tissues of diabetic db/db mice in response to dietary selenate supplementation. Fasting blood glucose levels increased continuously in db/db mice administered placebo (DMCtrl), but decreased gradually in selenate-supplemented db/db mice (DMSe) and approached normal levels after termination of the experiment. Pancreatic islet size was increased in DMSe mice compared with DMCtrl mice, resulting in a clear increase in insulin production and a doubling of plasma insulin concentration. Genes that encode proteins involved in key pancreatic β-cell functions, including regulation of β-cell proliferation and differentiation and insulin synthesis, were found to be specifically upregulated in DMSe mice. In contrast, apoptosis-associated genes were downregulated, indicating that islet function was protected by selenate treatment. Conversely, liver fat accumulation increased in DMSe mice together with significant upregulation of lipogenic and inflammatory genes. Genes related to detoxification were downregulated and antioxidant enzymatic activity was reduced, indicating an unexpected reduction in antioxidant defense capacity and exacerbation of fatty liver degeneration. Moreover, proteomic analysis of the liver showed differential expression of proteins involved in glucolipid metabolism and the endoplasmic reticulum assembly pathway. Taken together, these results suggest that dietary selenate supplementation in db/db mice decreased hyperglycemia by increasing insulin production and secretion; however, long-term hyperinsulinemia eventually led to reduced antioxidant defense capacity, which exacerbated fatty liver degeneration.http://europepmc.org/articles/PMC4077766?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chaoqun Wang Shulin Yang Ningbo Zhang Yulian Mu Hongyan Ren Yefu Wang Kui Li |
spellingShingle |
Chaoqun Wang Shulin Yang Ningbo Zhang Yulian Mu Hongyan Ren Yefu Wang Kui Li Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice. PLoS ONE |
author_facet |
Chaoqun Wang Shulin Yang Ningbo Zhang Yulian Mu Hongyan Ren Yefu Wang Kui Li |
author_sort |
Chaoqun Wang |
title |
Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice. |
title_short |
Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice. |
title_full |
Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice. |
title_fullStr |
Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice. |
title_full_unstemmed |
Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice. |
title_sort |
long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
There are conflicting reports on the link between the micronutrient selenium and the prevalence of diabetes. To investigate the possibility that selenium acts as a "double-edged sword" in diabetes, cDNA microarray profiling and two-dimensional differential gel electrophoresis coupled with mass spectrometry were used to determine changes in mRNA and protein expression in pancreatic and liver tissues of diabetic db/db mice in response to dietary selenate supplementation. Fasting blood glucose levels increased continuously in db/db mice administered placebo (DMCtrl), but decreased gradually in selenate-supplemented db/db mice (DMSe) and approached normal levels after termination of the experiment. Pancreatic islet size was increased in DMSe mice compared with DMCtrl mice, resulting in a clear increase in insulin production and a doubling of plasma insulin concentration. Genes that encode proteins involved in key pancreatic β-cell functions, including regulation of β-cell proliferation and differentiation and insulin synthesis, were found to be specifically upregulated in DMSe mice. In contrast, apoptosis-associated genes were downregulated, indicating that islet function was protected by selenate treatment. Conversely, liver fat accumulation increased in DMSe mice together with significant upregulation of lipogenic and inflammatory genes. Genes related to detoxification were downregulated and antioxidant enzymatic activity was reduced, indicating an unexpected reduction in antioxidant defense capacity and exacerbation of fatty liver degeneration. Moreover, proteomic analysis of the liver showed differential expression of proteins involved in glucolipid metabolism and the endoplasmic reticulum assembly pathway. Taken together, these results suggest that dietary selenate supplementation in db/db mice decreased hyperglycemia by increasing insulin production and secretion; however, long-term hyperinsulinemia eventually led to reduced antioxidant defense capacity, which exacerbated fatty liver degeneration. |
url |
http://europepmc.org/articles/PMC4077766?pdf=render |
work_keys_str_mv |
AT chaoqunwang longtermsupranutritionalsupplementationwithselenatedecreaseshyperglycemiaandpromotesfattyliverdegenerationbyinducinghyperinsulinemiaindiabeticdbdbmice AT shulinyang longtermsupranutritionalsupplementationwithselenatedecreaseshyperglycemiaandpromotesfattyliverdegenerationbyinducinghyperinsulinemiaindiabeticdbdbmice AT ningbozhang longtermsupranutritionalsupplementationwithselenatedecreaseshyperglycemiaandpromotesfattyliverdegenerationbyinducinghyperinsulinemiaindiabeticdbdbmice AT yulianmu longtermsupranutritionalsupplementationwithselenatedecreaseshyperglycemiaandpromotesfattyliverdegenerationbyinducinghyperinsulinemiaindiabeticdbdbmice AT hongyanren longtermsupranutritionalsupplementationwithselenatedecreaseshyperglycemiaandpromotesfattyliverdegenerationbyinducinghyperinsulinemiaindiabeticdbdbmice AT yefuwang longtermsupranutritionalsupplementationwithselenatedecreaseshyperglycemiaandpromotesfattyliverdegenerationbyinducinghyperinsulinemiaindiabeticdbdbmice AT kuili longtermsupranutritionalsupplementationwithselenatedecreaseshyperglycemiaandpromotesfattyliverdegenerationbyinducinghyperinsulinemiaindiabeticdbdbmice |
_version_ |
1724861349808308224 |