Effect of prostaglandins against alloxan-induced cytotoxicity to insulin secreting insulinoma RIN cells in vitro

Anti-Apoptotic Effects of Arachidonic Acid and Prostaglandin E₂ in Pancreatic β-Cells

“…Thus, both AA and PGE 2 suppressed alloxan-induced cytotoxicity in RIN insulinoma cells in vitro and prevented alloxan-induced diabetes in vivo [22][23][24][25]. In addition, deletion of cPLA 2 expression in the non obese diabetic mouse model of Type 1 diabetes resulted in severe insulitis and an increased incidence of diabetes, consistent with cPLA 2 -mediated AA release playing a protective role in the pathogenesis of autoimmune diabetes [26].…”

“…AA and PGE 2 , the major PG synthe-sised by β-cells, are reported to protect against apoptosis in RIN insulin-secreting cells [22,23] and to prevent alloxan-induced diabetes in vivo [24,25], so in the current study we examined whether glucose-stimulated elevations in AA and up-regulation of COX2 play a causal role in the anti-apoptotic effects of glucose.…”

“…Thus, in addition to exerting anti-apoptotic effects in RIN cells [23], it has been reported that PGE 2 inhibits apoptosis in a variety of cell types including human colon cancer cells [8]], dendritic cells [9,33], oesophageal adenocarcinoma cells [34], and, most recently, mouse embryonic stem cells [10]. However, cytokines up-regulate COX2 in islets [35] and RINm5F cells [36] and it has been proposed that increased COX2 expression may contribute to islet dysfunction in diabetes [16].…”

“…In the current study we have identified mRNAs encoding EP2 and EP3 PGE 2 receptors in MIN6 cells. EP2 receptors are linked to cyclic AMP generation [43], and it has been proposed that PGE 2 protects RIN insulin-secreting cells against alloxan-induced apoptosis through its ability to increase cyclic AMP [23], so it is possible that PGE 2 acts through a similar mechanism in MIN6 cells and mouse islets.…”

“…To determine whether PGE 2 could confer protection against apoptosis in MIN6 cells, as it has been reported to do in RIN insulinoma cells [23], MIN6 cells were maintained in culture for 48 hours with 50µM NS-398 in the absence or presence of PGE 2 and then caspase-3 activity levels were measured. It can be seen from Figure 5a that NS-398 increased caspase-3 activity at 2.5mM glucose and concurrent exposure to PGE 2 (0.2-5µM) rescued the NS-398-induced rise in apoptosis in a concentration-dependent manner, such that caspase-3 activity in the presence of 50µM NS-398 and 5µM PGE 2 was not significantly higher than that at 2.5mM glucose alone (P>0.2).…”