Molecular and cellular endocrinology
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Mol. Cell. Endocrinol. · Jan 2013
Differential and day-time dependent expression of nuclear receptors RORα, RORβ, RORγ and RXRα in the rodent pancreas and islet.
The retinoic-acid-related receptor family of orphan receptors (RORs) act as transcriptional activators or repressors. One of their functions involves integrated actions within circadian oscillators, particularly of the periphery. The present paper describes differential expression of the orphan receptors RORα, RORβ and RORγ and of the nuclear retinoid receptor RXRα in the pancreas and islet of rats. ⋯ Quantitative RT-PCR revealed circadian expression in the rat pancreas for RORγ, RORα and RXRα, but not for RORβ. Circadian expression of RORγ mRNA was verified in mouse pancreas and in rat INS-1 β cells by serum shock experiments. The results point to differential and circadian expression and thus cell-type-specific functions of RORα and RORγ in islet cells secreting glucagon or insulin.
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Mol. Cell. Endocrinol. · Jan 2013
Curcumin ameliorates diabetic nephropathy by inhibiting the activation of the SphK1-S1P signaling pathway.
Curcumin, a major polyphenol from the golden spice Curcuma longa commonly known as turmeric, has been recently discovered to have renoprotective effects on diabetic nephropathy (DN). However, the mechanisms underlying these effects remain unclear. We previously demonstrated that the sphingosine kinase 1-sphingosine 1-phosphate (SphK1-S1P) signaling pathway plays a pivotal role in the pathogenesis of DN. ⋯ Furthermore, curcumin inhibited the DNA-binding activity of activator protein 1 (AP-1), and c-Jun small interference RNA (c-Jun-siRNA) reversed the HG-induced up-regulation of SphK1. These findings suggested that down-regulation of the SphK1-S1P pathway is probably a novel mechanism by which curcumin improves the progression of DN. Inhibiting AP-1 activation is one of the therapeutic targets of curcumin to modulate the SphK1-S1P signaling pathway, thereby preventing diabetic renal fibrosis.