Modulation of hyperglycemia, insulin resistance responses and gut microbiota composition in type 2 diabetic mice by capsicum residue soluble dietary fiber

Type 2 diabetes mellitus (T2DM) poses substantial health risks, emphasizing the need to identify natural ingredients from biological sources that can alleviate its symptoms. Capsicums produce a large amount of capsicum residue (CR) by-products during processing, which are underutilized. CR is rich in soluble dietary fiber (SDF) and has shown potential as an adjunctive hypoglycemic dietary supplement. This study investigated the structure of capsicum residue soluble dietary fiber (CR-SDF), its hypoglycemic effects in T2DM mice fed a high-fat diet combined with streptozotocin, and its hypoglycemic mechanism through glucose and lipid metabolism indexes, blood biochemistry indexes, short-chain fatty acids (SCFAs), gut microbiota, and the expression levels of genes related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. The results indicated that CR-SDF mainly contains galacturonic acid, glucose, and galactose. CR-SDF was loose and porous with a rough surface. It exhibited characteristic polysaccharide absorption peaks and a cellulose I crystalline structure. After four weeks of CR-SDF intervention, T2DM mice showed improvements in glucose and lipid levels, insulin resistance, and liver and pancreas health. Analysis of fecal SCFAs revealed increased concentrations in diabetic mice after CR-SDF intervention, while fecal microbiota analysis showed enrichment of beneficial bacteria (<i>Bacteroides</i> and <i>Akkermansia</i>) and inhibition of harmful bacteria (norank_f__<i>Lachnospiraceae</i>, unclassified_f__<i>Lachnospiraceae</i>, and <i>Aerococcus</i>). In addition, RT-PCR results indicated that CR-SDF upregulated the relative mRNA expression levels of insulin receptor substrate-1, PI3K, Akt, and glucose transporter 2. These findings suggest that CR-SDF could be an effective intervention for T2DM by improving gut microbiota dysbiosis and promoting intestinal fermentation to produce more SCFAs, which drive insulin secretion to improve the efficiency of blood glucose utilization. Moreover, CR-SDF promotes insulin signaling and improves insulin resistance by activating the PI3K/AKT signaling pathway, thereby lowering blood glucose.