The efficacy of SPA0355 in protecting beta cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes.
- Author:
Ui Jin BAE
1
;
Mi Young SONG
;
Hyun Young JANG
;
Hyo Jin GIM
;
Jae Ha RYU
;
Sang Myeong LEE
;
Raok JEON
;
Byung Hyun PARK
Author Information
1. Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea. bhpark@jbnu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
beta-cell;
cytokine;
NF-kappaB;
SPA0355;
STAT;
type 1 diabetes
- MeSH:
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
- From:Experimental & Molecular Medicine
2013;45(11):e51-
- CountryRepublic of Korea
- Language:English
-
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.
