A protective effect of endomorphins on the oxidative injury of islet.
The antioxidative capacity of endomorphins (EMs), endogenous μ-opioid receptor agonists, has been demonstrated by IN VIVO assays. In this study, we attempt to evaluate the effects of endomorphin 1 (EM1) and endomorphin 2 (EM2) on pancreatic islet injuries induced by streptozotocin (STZ), alloxan (ALX) and H(2)O(2), respectively. Wistar rats' islets were isolated and purified. The function of the islet cells, the insulin response to glucose stimulation was examined by insulin Radio Immuno Assay and the cell viability was measured by MTT assay. DNA fragments were performed to evaluate the apoptosis, while the cell cycle distribution was analyzed by PI staining flow cytometric analysis. Furthermore, the islet were treated with EM1, EM2 or ALX for 24 h, and the expression of p53 and p21 protein were determined by Western blot. The results showed that STZ, ALX, and H(2)O(2) displayed clear concentration-dependent inhibitory effects on the pancreatic islet cells. While EMs improved the viability of islet induced by STZ, ALX or H(2)O(2), and EMs enhanced insulin accumulation of the cell supernatant after ALX and STZ stimulation. Our data also showed both that EMs inhibited cell apoptosis and cell cycle G1 arrest induced by STZ and ALX through down-regulaing p53 and p21 expression. Taken together, these results demonstrate that EMs can protect islet cells from STZ, ALX and H(2)O(2) induced injuries. Our observations imply that the endomorphins may have protective effects on islet cells oxidative injury.
Tian
L M
LM
Department of Endocrinology, People's Hospital of Gansu Province, Lanzhou, PR China.
Liu
J
J
Sun
X L
XL
Gao
C X
CX
Fan
Y
Y
Guo
Q
Q
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D019610:Cytoprotection; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000517:prevention & control; D005947:Glucose / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D007004:Hypoglycemic Agents; D007328:Insulin; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D016159:Tumor Suppressor Protein p53; C105293:endomorphin 1; C105294:endomorphin 2; D006861:Hydrogen Peroxide; D016283:Proto-Oncogene Proteins p21(ras); D005947:Glucose