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Diclofenac belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs), which are amongst the most frequently prescribed drugs to treat fever, pain and inflammation. Despite the presence of NSAIDs on the pharmaceutical market for several decades, epidemiological studies have shown new clinical applications of NSAIDs, and new mechanisms of their action were discovered. The unfolded protein response (UPR) activated under endoplasmic reticulum (ER) stress is involved in the pathophysiology of many diseases and may become a drug target, therefore, the study evaluated the effects of diclofenac on the tunicamycin-induced UPR pathways in endothelial cells. RT PCR analysis showed that diclofenac significantly inhibited activation of ER stress-responsive genes, i.e., CHOP/DITT3, GRP78/HSPA5 and DNAJB9. Additionally, the drug diminished the significant upregulation and release of the GRP78 protein, as evaluated using the ELISA assay, which was likely to be involved in the mechanism of the UPR activation resulting in apoptosis induction in endothelial cells. These results suggest the value of diclofenac as a factor capable of restoring the ER homeostasis in endothelial cells by diminishing the UPR.

Introduction: Literature reports link psoriasis with insulin resistance characteristic for type 2 diabetes. However, this condition may also affect the clinical course of type 1 diabetes (T1D)., Aim: To investigate whether children with type 1 diabetes mellitus (T1D) and psoriasis have a different course of diabetes., Methods: We evaluated patients diagnosed with T1D in the years 2002-2011 for the presence of psoriasis and matched them 1:10 with T1D-only patients by sex and duration of diabetes using propensity score. We collected T1D-onset parameters and metabolic control surrogates from six months after T1D diagnosis., Results: We identified 14 patients with psoriasis and matched 140 controls, of whom 129 (68 boys) were eligible for the analysis. At onset T1D+psoriasis patients showed higher concentration of C-peptide than controls (median: 0.38ng/ml vs 0.15ng/ml, p=0.02). Six months later, they had non-significantly lower HbA1c (6.0 vs 6.6%, p=0.11), TC (143mg/dl vs 159mg/dl, p=0.14) HDL (54.5mg/dl vs 59mg/dl, p=0.11)., Conclusions: Patients with T1D and psoriasis present higher endogenous insulin secretion at T1D onset and a tendency for better glycemic control during the first 6 months., (© Polish Society for Pediatric Endocrinology and Diabetology.)