Effect of the acute and chronic administration of Lupinus albus β-conglutin on glycaemia, circulating cholesterol, and liver gene expression profile

Constituents of lupin seeds, like γ-conglutin and lupanine, have gained attention as potential complementary treatments for the management of dysglycaemia. Notwithstanding, the effect of other lupin components on carbohydrate metabolism, including β-conglutin protein, has received little attention. Here, we investigated the influence of the acute and chronic administration of β-conglutin on glycaemia modulation in normal and streptozotocin induced-to-diabetes rats. To identify potential molecular targets and pathways involved in this biological response, we analysed the liver transcriptome modulation exerted by β-conglutin in diabetes-induced rats using DNA microarrays. The acute administration of β-conglutin reduced the incremental area under the curve of glycaemia in normal and diabetes-induced animals. In a seven-day study with diabetic animals, glycaemia increased significantly in non-treated animals but remained unchanged in animals treated with a daily dose of β-conglutin. Noteworthy, total cholesterol was significantly lower at the end of the experimental period (−21.8%, p = 0.039). Results of the microarray test and gene ontology analyses revealed several targets and pathways modulated after β-conglutin treatment, including a down-regulation of Jun kinase activity. Moreover, our data indicate that targets related to oxidative stress, inflammation, and estrogenic activity might orchestrate these metabolic effects. In conclusion, our findings show that β-conglutin may be useful to manage postprandial glycaemia and reduce cholesterol levels under the dysglycaemia stage. We identified and proposed new potential molecular targets for further research related to the mechanism of action of β-conglutin.羽扇豆种子中的成分（如γ-伴羽扇豆球蛋白（γ-conglutin）与羽扇豆宁（lupanine））作为治疗糖代谢异常的潜在辅助疗法，已受到广泛关注。尽管如此，包括β-伴羽扇豆球蛋白（β-conglutin）在内的其他羽扇豆成分对碳水化合物代谢的影响却鲜有研究。 本研究探讨了急性与慢性给予β-伴羽扇豆球蛋白对正常大鼠及链脲佐菌素（streptozotocin）诱导的糖尿病大鼠血糖调控的影响。为明确该生物学效应相关的潜在分子靶点与通路，本研究通过DNA微阵列（DNA microarray）技术分析了β-伴羽扇豆球蛋白对糖尿病大鼠肝脏转录组的调控作用。 急性给予β-伴羽扇豆球蛋白可降低正常及糖尿病模型动物的血糖曲线下增量面积。 在为期7天的糖尿病动物实验中，未给药组动物血糖显著升高，而每日给予β-伴羽扇豆球蛋白的给药组动物血糖则保持稳定。 值得注意的是，实验结束时给药组总胆固醇水平显著降低（下降21.8%，p=0.039）。 微阵列检测及基因本体（gene ontology）分析结果显示，β-伴羽扇豆球蛋白处理后有多个靶点与通路发生调控变化，其中包括Jun激酶活性的下调。此外，本研究数据显示，与氧化应激、炎症及雌激素活性相关的靶点可能介导了上述代谢效应。 综上，本研究结果表明，β-伴羽扇豆球蛋白可用于调控糖代谢异常状态下的餐后血糖，并降低胆固醇水平。本研究还鉴定并提出了多个新的潜在分子靶点，可为后续β-伴羽扇豆球蛋白作用机制的相关研究提供参考。