COX-2 inhibition prevents insulin-dependent diabetes in low-dose streptozotocin-treated mice

Biochem Biophys Res Commun. 2000 Jul 5;273(2):699-704. doi: 10.1006/bbrc.2000.2959.

Abstract

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease believed to be caused by an inflammatory process in the pancreas leading to selective destruction of the beta cells. Inducible cyclooxygenase (COX-2) is expressed under inflammatory conditions and its product prostaglandin E(2) (PGE(2)) is an important inflammation mediator. We report here that administration of the selective COX-2 inhibitor NS-398 prevents the onset of diabetes in mice brought on by multiple low-doses of streptozotocin (STZ). Histological observations indicated that STZ-mediated destruction of beta cells was prevented by NS-398 treatment. Delayed (day 3) administration of NS-398 was also protective in this model. No protective effect was observed when NS-398 was administered prior to a high, toxic dose of STZ. These results demonstrate the critical importance of COX-2 activity in autoimmune destruction of beta cells, and point to the fact that COX-2 inhibition can potentially develop into a preventive therapy against IDDM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / administration & dosage
  • Cyclooxygenase Inhibitors / pharmacology*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Dinoprostone / metabolism
  • Glycated Hemoglobin A / metabolism
  • Indomethacin / pharmacology
  • Isoenzymes / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nitrobenzenes / administration & dosage
  • Nitrobenzenes / pharmacology
  • Pancreas / drug effects
  • Pancreas / pathology
  • Prostaglandin-Endoperoxide Synthases / pharmacology*
  • Streptozocin / administration & dosage
  • Streptozocin / toxicity
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology
  • Time Factors

Substances

  • Blood Glucose
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Glycated Hemoglobin A
  • Isoenzymes
  • Nitrobenzenes
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Streptozocin
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Indomethacin