title: Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice.
abstract: 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.
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei, P. R. China; State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Shulin
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Ningbo
authors.initials: N
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Mu
authors.affiliation: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ren
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei, P. R. China.
authors.forename: Yefu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Kui
authors.initials: K
authors.lastname: Li
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D019587:Dietary Supplements; D005234:Fatty Liver / Q000139:chemically induced* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006946:Hyperinsulinism / Q000139:chemically induced* / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D010179:Pancreas / Q000187:drug effects; D064586:Selenic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D064586:Selenic Acid