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.