Exp Mol Med.  2013 Nov;45(11):e51.

The efficacy of SPA0355 in protecting beta cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes

• Bae UJ
• Song MY
• Jang HY
• Gim HJ
• Ryu JH
• Lee SM
• Jeon R
• Park BH

Abstract

Cytokines activate several inflammatory signals that mediate beta-cell destruction. We recently determined that SPA0355 is a strong anti-inflammatory compound, thus reporting its efficacy in protecting beta cells from various insults. The effects of SPA0355 on beta-cell survival were studied in RINm5F cells and primary islets. The protective effects of this compound on the development of type 1 diabetes were evaluated in non-obese diabetic (NOD) mice. SPA0355 completely prevented cytokine-induced nitric oxide synthase (iNOS) expression and cytotoxicity in RINm5F cells and isolated islets. The molecular mechanism of SPA0355 inhibition of iNOS expression involves the inhibition of nuclear factor kappaB and Janus kinase signal transducer and activator of transcription pathways. The protective effects of SPA0355 against cytokine toxicity were further demonstrated by normal insulin secretion and absence of apoptosis of cytokine-treated islets. In experiments with NOD mice, the occurrence of diabetes was efficiently reduced when the mice were treated with SPA0355. Therefore, SPA0355 might be a valuable treatment option that delays the destruction of pancreatic beta cells in type 1 diabetes.

Keyword

beta-cell; cytokine; NF-kappaB; SPA0355; STAT; type 1 diabetes

MeSH Terms

Animals
Apoptosis
Benzoxazines/pharmacology/*therapeutic use
Cell Line
Cell Survival
Cells, Cultured
Diabetes Mellitus, Experimental/*prevention & control
Insulin-Secreting Cells/*drug effects/metabolism
Janus Kinases/genetics/metabolism
Mice
Mice, Inbred NOD
NF-kappa B/genetics/metabolism
Nitric Oxide Synthase Type II/genetics/metabolism
Rats
Thiourea/*analogs & derivatives/pharmacology/therapeutic use
Benzoxazines
NF-kappa B
Nitric Oxide Synthase Type II
Janus Kinases
Thiourea