PTGS-2–PTGER2/4 Signaling Pathway Partially Protects From Diabetogenic Toxicity of Streptozotocin in Mice

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FIG. 5.
FIG. 5.

Effects of STZ in PTGER–deficient mice. A: Expression of PTGER mRNA in mouse pancreas and islets. RNA was prepared from the pancreas and islets of wild-type mice, and mRNA expression for PGE2 receptor types PTGER1, PTGER2, PTGER3, and PTGER4 was determined by PCR. As a control, β-actin was included. A representative analysis from three experiments is shown. B: Hyperglycemic effect of STZ in PTGER-deficient mice. Data are shown as mean ± SEM; n = 6. *P < 0.05 vs. vehicle; #P < 0.05 vs. STZ-treated PTGER2−/−. C: Effect of STZ on plasma insulin concentration in PTGER2- and PTGER4-deficient mice. Data are shown as mean ± SEM; n = 6. *P < 0.05 vs. vehicle; #P < 0.05 vs. STZ-treated PTGER2−/−. D: Kaplan-Meier survival analysis in PTGER2−/− and PTGER4−/− mice after application of STZ. In comparison, data obtained for PTGS-2−/− mice are included. Mice were kept under standard conditions for 10 days. Data are shown as mean ± SEM; n = 10. Wild-type (CTRL), PTGER1−/−, PTGER2−/−, PTGER3−/−, and PTGER4−/− mice were treated by a single injection of STZ (200 mg/kg BW), and on day 4, blood glucose or insulin was measured. To block PTGER2 and PTGER4 signaling pathways, we treated PTGER2−/− mice with PTGER4-selective antagonist ONO-AE3-208 (25 mg/kg) 1 day before STZ application and then daily.

This Article

  1. Diabetes vol. 61 no. 7 1879-1887