Guangdong Provincial Key Laboratory of Marine Biotechnology, Department of Biology, College of Science, Shantou University, Shantou, Guangdong 515063, PR China.
Guangdong Provincial Key Laboratory of Marine Biotechnology, Department of Biology, College of Science, Shantou University, Shantou, Guangdong 515063, PR China.
Int J Biol Macromol. 2024 Nov;279(Pt 3):135422. doi: 10.1016/j.ijbiomac.2024.135422. Epub 2024 Sep 6.
Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia. Type 2 diabetes mellitus (T2DM) represents approximately 90 % of all DM cases and is primarily caused by an imbalance in blood glucose homeostasis due to inadequate insulin secretion or insulin resistance. This study explores the potential therapeutic effects of chitosan guanidine (CSG) on a T2DM mouse model. The findings reveal that CSG significantly enhances oral glucose tolerance (OGTT) and insulin sensitivity (ITT), reduces fasting blood glucose (FBG) levels, and suppresses the expression of proinflammatory cytokines in T2DM mice. These changes improve insulin resistance and diminish inflammation. Additionally, CSG markedly ameliorates lipid metabolism disorders, lowers total cholesterol (TC) and triglyceride (TG) levels, and inhibits hepatic fat accumulation. 16S rRNA and Spearman correlation analyses indicate that CSG promotes the relative abundance of probiotic genera such as Bacteroidota, Patescibacteria, Actinobacteria, and Cyanobacteria. These bacteria are positively correlated with short-chain fatty acids (SCFAs) and high-density lipoprotein cholesterol (HDLC) levels. Conversely, CSG reduces the relative abundance of pathogenic bacteria, including Proteobacteria and Ralstonia, leading to an improved intestinal microbial community composition in T2DM mice and alleviating T2DM symptoms. These results suggest that CSG holds significant potential as a non-insulin therapeutic agent for diabetes management.
糖尿病(DM)是一种以高血糖为特征的慢性代谢性疾病。2 型糖尿病(T2DM)约占所有 DM 病例的 90%,主要是由于胰岛素分泌不足或胰岛素抵抗导致血糖稳态失衡引起的。本研究探讨了壳聚糖胍(CSG)对 T2DM 小鼠模型的潜在治疗作用。研究结果表明,CSG 可显著增强 T2DM 小鼠的口服葡萄糖耐量(OGTT)和胰岛素敏感性(ITT),降低空腹血糖(FBG)水平,并抑制促炎细胞因子的表达。这些变化可改善胰岛素抵抗和炎症。此外,CSG 可明显改善脂代谢紊乱,降低总胆固醇(TC)和甘油三酯(TG)水平,并抑制肝脂肪堆积。16S rRNA 和 Spearman 相关分析表明,CSG 可促进厚壁菌门、巴氏杆菌门、放线菌门和蓝藻门等益生菌属的相对丰度增加。这些细菌与短链脂肪酸(SCFAs)和高密度脂蛋白胆固醇(HDLC)水平呈正相关。相反,CSG 降低了包括变形菌门和罗尔斯通氏菌在内的致病菌的相对丰度,改善了 T2DM 小鼠的肠道微生物群落组成,缓解了 T2DM 症状。这些结果表明,CSG 作为一种非胰岛素治疗糖尿病的药物具有重要的潜力。