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AGI-1067，一种新型的抗氧化剂和抗炎剂，可增强胰岛素分泌并保护小鼠胰岛。

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

机构信息

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

出版信息

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

DOI:10.1016/j.mce.2010.02.041
PMID:20211684
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2875300/
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.

摘要

抗氧化剂和抗炎化合物 AGI-1067（琥珀酸 Bucol）具有作为口服抗糖尿病药物的潜力。AGI-1067 降低 H(b)A1c，改善空腹血浆葡萄糖，并减少新发糖尿病。我们研究了 AGI-1067 对体外小鼠胰岛的可能作用。用 10 microM AGI-1067 预处理可增加葡萄糖刺激的胰岛素分泌（11 mM），而不影响基础（3 mM）葡萄糖中的分泌。AGI-1067 增强了 7 mM 和 11 mM 葡萄糖刺激的细胞内钙反应，但在 28 mM 或基础葡萄糖中没有作用。AGI-1067 预处理的胰岛也显示出对低剂量甲基丙酮酸和α-酮异己酸的钙反应增强，但对高剂量没有作用。AGI-1067 对葡萄糖刺激钙的介导作用在持续二氮嗪暴露期间得以维持，表明其对 K(ATP)-通道非依赖性途径的作用。AGI-1067 还减少了细胞因子诱导的胰岛细胞死亡和 iNOS 的表达，iNOS 是细胞因子信号中的关键组成部分。这是首例关于一类新型潜在抗糖尿病药物对胰腺胰岛的直接刺激和保护作用的报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/78e6676b270e/nihms-191101-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/7b67efb7965a/nihms-191101-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/1e43040d1f16/nihms-191101-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/c7f0892d0a87/nihms-191101-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/8e855a35322c/nihms-191101-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/488ab54d5e5b/nihms-191101-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/28d97e9eebfa/nihms-191101-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/70ea8fa9a4ba/nihms-191101-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/35e5c37ad72c/nihms-191101-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/78e6676b270e/nihms-191101-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/7b67efb7965a/nihms-191101-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/1e43040d1f16/nihms-191101-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/c7f0892d0a87/nihms-191101-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/8e855a35322c/nihms-191101-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/488ab54d5e5b/nihms-191101-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/28d97e9eebfa/nihms-191101-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/70ea8fa9a4ba/nihms-191101-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/35e5c37ad72c/nihms-191101-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f188/2875300/78e6676b270e/nihms-191101-f0009.jpg

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