Dihydroavenanthramide D protects pancreatic beta-cells from cytokine and streptozotocin toxicity.
Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Although its anti-inflammatory, antiatherosclerotic, and antioxidant effects have been reported, the effect of DHAvD on type 1 diabetes is unknown. Therefore, in this study, the effect of DHAvD on cytokine- or streptozotocin-induced beta-cell damage was investigated. Treatment of RINm5F insulinoma cells or isolated islets with IL-1beta and IFN-gamma induced beta-cell damage through a NF-kappaB-dependent signaling pathway. DHAvD-pretreated RINm5F cells or islets showed resistance to cytokine toxicity, namely suppressed nitric oxide (NO) production, reduced the inducible form of NO synthase expression, and decreased beta-cell destruction and the normal insulin secretion capacity. Furthermore, pretreatment with DHAvD blocked the development of type 1 diabetes in streptozotocin-treated mice. Prior injection with DHAvD maintained a normal range of plasma glucose and insulin, and retained immunoreactivity for insulin in the pancreas. These results suggest that DHAvD may be used to preserve functional beta-cell mass.
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Na
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Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
Song
Mi-Young
MY
Lee
Young-Rae
YR
Choi
Ha-Na
HN
Kwon
Kang-Beom
KB
Park
Jin-Woo
JW
Park
Byung-Hyun
BH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D018554:Avena / Q000737:chemistry; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D019610:Cytoprotection; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000633:toxicity; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D013311:Streptozocin / Q000037:antagonists & inhibitors / Q000633:toxicity; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016207:Cytokines; D053583:Interleukin-1beta; D016328:NF-kappa B; D062367:ortho-Aminobenzoates; C532345:dihydroavenanthramide D; D013311:Streptozocin; D007371:Interferon-gamma