Microarray analysis of insulin-regulated gene expression in the liver: the use of transgenic mice co-expressing insulin-siRNA and human IDE as an animal model.

To characterize the changes in global gene expression in the livers of H1/siRNAinsulin-CMV/hIDE transgenic (Tg) mice in response to the reduced bioavailability of insulin, total RNA extracted from the livers of 20-week-old Tg and non-Tg mice was converted to cDNA, labeled with biotin and hybridized to oligonucleotide microarrays. The microarray results were confirmed by a real-time reverse transcription-polymerase chain reaction. Two hundred and fifty-one and 73 genes were up- and down-regulated, respectively by insulin in H1/siRNAinsulin-CMV/hIDE Tg mice compared to the controls.

Selenium acts as an insulin-like molecule for the down-regulation of diabetic symptoms via endoplasmic reticulum stress and insulin signalling proteins in diabetes-induced non-obese diabetic mice.

To investigate whether selenium (Sel) treatment would impact on the onset of diabetes,we examined serum biochemical components including glucose and insulin,endoplasmic reticulum (ER) stress and insulin signalling proteins, hepatic C/EBP-homologous protein (CHOP) expression and DNA fragmentation in diabetic and non- diabetic conditions of non-obese diabetic (NOD) mice. We conclude that (i) Sel treatment induced insulin-like effects in lowering serum glucose level in Sel-treated NOD mice, (ii) Sel-treated mice had significantly decreased serum biochemical components associated with liver damage and lipid metabolism, (iii) Sel treatment led to the activation of the ER stress signal through the phosphorylation of JNK and eIF2 protein and insulin signal mechanisms through the phosphorylation of Akt and PI3 kinase, and (iv) Sel-treated mice were significantly relieved apoptosis of liver tissues indicated by DNA fragmentation assay in the diabetic NOD group. These results suggest that Sel compounds not only serve as insulin-like molecules for the downregulation of glucose level and the incidence of liver damage, but may also have the potential for the development of new drugs for the relief of diabetes by activating the ER stress and insulin signalling pathways.