Cγ and lupanine enhances in vivo the antidiabetic effect and involves modulation of the liver gene expression profile. Cγ and lupanine enhances in vivo the antidiabetic effect and involves modulation of the liver gene expression profile

Previous studies have individually shown the antidiabetic potential of gamma conglutin (Cγ) and lupanine from lupins. Until now, the influence of combines both compounds and the effective dose of the combination is not assessed. Moreover, the resulting gene profile from this novel combination remains to be explored. Therefore, we proposed to study different dose combinations of Cγ and lupanine by the oral glucose tolerance test (OGTT) to identify the greater antidiabetic effect on the T2D rat model. Later, we administered the selected dose combination for a week. Finally, we evaluated the gene expression profile using DNA microarrays and its bioinformatic analysis. We found that the combination of 28 mg/kg BW Cγ + 20 mg/kg BW lupanine positively influences the expression of Pdk4, Ppargc1a, Foxo1, and Foxo3 genes. The reestablishment of Pdk4 gene expression is involved in several biological processes associated with regulation, metabolism, and homeostasis of glucose and fatty acids. For the first time, we reported the beneficial effect of the combination of two functional lupin compounds in a T2D rat model. Nevertheless, further studies are needed to investigate the pharmacokinetics and pharmacodynamics of the Cγ + lupanine combination. Gene expression analysis of RNA samples from liver tissue of healthy and diabetic-induced rats. Overall design: Three biological replicates of liver total RNA pools were prepared for each experimental group: healthy rat group, type 2 diabetic control group, and type 2 diabetic rats treated with 28 mg/kg BW Cγ + 20 mg/kg BW lupanine. Each pool consisted of the mixture of RNA isolated from three different animals. A total of three technical replicates (derived from the RNA of nine animals per group) were processed for hybridization into the Affymetrix´s Rat Transcriptome Array 1.0 (Affymetrix, Santa Clara, CA, USA) at the Microarray Unit of the National Institute of Genomic Medicine (INMEGEN), Mexico. The procedures of hybridization and scanning of the microarray were performed according to GeneChipTM Whole Transcript (WT) Expression Arrays User Guide of Affymetrix Corporation. The gene expression files were processed and analyzed with the Applied Biosystem-sTM Transcriptome Analysis Console 4.0.2 (TAC, ThermoFisher, CA, USA). Gene expression data were RMA normalized, and differential expression determined with the following parameters: RMA+DABG (Rattus norvegicus) and expression analysis settings: Fold Change 2, p-value < 0.05, and ANOVA method: ebayes. For functional enrichment analysis, STRING software was used to analyze differentially expressed targets interactions. Gene Ontology (GO), KEGG pathways, and WikiPathways analysis were performed.