Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the past decade a number of studies suggested that type 1 diabetes mellitus is an oxidative stress influenced disease. Paraoxonase 1 enzyme plays a crucial role in antiatherogenic-antioxidant circle. The aim of our study was to examine the possible differences in paraoxonase 1 enzymatic activities in diabetic children associated other autoimmune diseases versus a control group. Another objective of the study was to determine if there is any difference according to the gender in paraoxonase 1 activities (arylesterase and paraoxonase activities). Paraoxonase 1 activities were determined in 51 diabetic children and 36 healthy controls. In diabetic children we determined also the C-peptide level. The paraoxonase 1 arylesterase activity was lower in diabetic females compared with diabetic males. The level of C-peptide is in an inverse correlation with the years of the disease. The paraoxonase activities have a correlation with the level of insulin antibodies in type I diabetic children. Our data suggest that paraoxonase enzymatic pattern may be different in these two activities. PON1 arylesterase activity may exhibit a tendency to low levels in women in comparison to men. The C-peptide level is a valuable tool in assessing the restant beta cell function.
 ...
PMID:Immunological manifestations in type I diabetic children. 2321 Mar 23

Pancreatic beta cell destruction and dysfunction induced by cytokines is a major cause of type 1 diabetes. Paraoxonase 1 (PON1), an arylesterase with antioxidant activity, has been shown to play an important role in preventing the development of diabetes in transgenic mice. However, no studies have examined the anti-diabetic effect of PON1 delivered to beta cells using protein transduction. In this study, we expressed the cell-permeable PON1 fused with PEP-1 protein transduction domain (PEP-1-PON1) to investigate whether transduced PEP-1-PON1 protects beta cells against cytokine-induced cytotoxicity. PEP-1-PON1 was effectively delivered to INS-1 cells and prevented cytokine-induced cell destruction in a dose-dependent manner. Transduced PEP-1-PON1 significantly reduced the levels of reactive oxygen species (ROS) and nitric oxide (NO), DNA fragmentation, and expression of inflammatory mediators, endoplasmic reticulum (ER) stress proteins, and apoptosis-related proteins in cytokine-treated cells. Moreover, transduced PEP-1-PON1 restored the decrease in basal and glucose-stimulated insulin secretion induced by cytokines. These data indicate that PEP-1-PON1 protects beta cells from cytokine-induced cytotoxicity by alleviating oxidative/nitrosative stress, ER stress, and inflammation. Thus, PEP-1-mediated PON1 transduction might be an effective method to reduce the extent of destruction and dysfunction of pancreatic beta cells in autoimmune diabetes. [BMB Reports 2018; 51(10): 539-544].
 ...
PMID:PEP-1-paraoxonase 1 fusion protein prevents cytokine-induced cell destruction and impaired insulin secretion in rat insulinoma cells. 3026 41