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Mol Cell Endocrinol. 2010 Jul 29;323(2):246-55. doi: 10.1016/j.mce.2010.02.041. Epub 2010 Mar 6.

AGI-1067, a novel antioxidant and anti-inflammatory agent, enhances insulin release and protects mouse islets.

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  • 1Department of Medicine, University of Virginia, VA 22908, USA.

Abstract

The antioxidant and anti-inflammatory compound AGI-1067 (succinobucol) has potential as an oral anti-diabetic agent. AGI-1067 reduces H(b)A1c, improves fasting plasma glucose, and reduces new-onset diabetes. We investigated AGI-1067 for possible effects on mouse pancreatic islets in vitro. Pretreatment with 10 microM AGI-1067 increased glucose-stimulated insulin secretion (11 mM) without affecting secretion in basal (3 mM) glucose. AGI-1067 enhanced the intracellular calcium response to glucose stimulation in 7 mM and 11 mM glucose, but had no effect in 28 mM or basal glucose. AGI-1067-pretreated islets also showed enhanced calcium responses to methyl pyruvate and alpha-ketoisocaproate at low doses, but not high doses. The AGI-1067-mediated effects on glucose-stimulated calcium were maintained during continuous diazoxide exposure, suggesting effects on the K(ATP)-channel-independent pathway. AGI-1067 also reduced cytokine-induced islet cell death and expression of iNOS, a key component in cytokine signaling. This is the first report of direct stimulatory and protective effects of a first-in-class potential anti-diabetic agent on pancreatic islets.

2010 Elsevier Ireland Ltd. All rights reserved.

PMID:
20211684
[PubMed - indexed for MEDLINE]
PMCID:
PMC2875300
Free PMC Article
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