In-Depth Investigation of the Mechanisms Underlying Recrystallized Resistant Starch-Induced Amelioration of Insulin Resistance in T2DM Mice via Liver Metabolomics Integrated with Colon Transcriptomics

Kunjie Xu, Fangfei Ji, Yuexin Yang, Ranran Chang* and Aiguo Ma, 
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Abstract

The effects of A-type recrystallized resistant starch (ARS) on ameliorating insulin resistance in type 2 diabetes mellitus (T2DM) mice were investigated using liver metabolomics integrated with colon transcriptomics. Mice supplied with medium and high ARS doses exhibited lower fasting serum insulin and HOMA-IR, reduced insulin resistance, and elevated HOMA-IS and HOMA-β levels, indicating that ARS can improve insulin sensitivity. ARS significantly reduced liver triglyceride and nonesterified fatty acid levels, liver fat accumulation, and hepatic interleukin-1β and interleukin-6 levels in T2DM mice. Liver metabolomic analysis revealed that ARS significantly modulated the cysteine-methionine and glycerophospholipid metabolic pathways. Moreover, ARS may enhance inhibition of the PI3K/Akt, NF-κB, AMPK, type II diabetes mellitus, and insulin resistance pathways by regulating the expression of Tnf-α, Socs1, Irs3, and Lipe, thereby ameliorating insulin resistance in T2DM mice. Thus, our findings support the potential preventive and therapeutic effects of recrystallized resistant starch in T2DM treatment.

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通过肝脏代谢组学与结肠转录组学整合深入研究重结晶抗性淀粉诱导 T2DM 小鼠胰岛素抵抗改善的机制
采用肝脏代谢组学和结肠转录组学方法研究了a型再结晶抗性淀粉(ARS)对2型糖尿病(T2DM)小鼠胰岛素抵抗的改善作用。给予中、高剂量ARS的小鼠表现出较低的空腹血清胰岛素和HOMA- ir,降低胰岛素抵抗,升高HOMA- is和HOMA-β水平,表明ARS可以改善胰岛素敏感性。ARS显著降低T2DM小鼠肝脏甘油三酯和非酯化脂肪酸水平、肝脏脂肪堆积以及肝脏白细胞介素-1β和白细胞介素-6水平。肝脏代谢组学分析显示,ARS显著调节了半胱氨酸-蛋氨酸和甘油磷脂的代谢途径。此外,ARS可能通过调节Tnf-α、Socs1、Irs3和Lipe的表达,增强对PI3K/Akt、NF-κB、AMPK、II型糖尿病和胰岛素抵抗通路的抑制,从而改善T2DM小鼠的胰岛素抵抗。因此,我们的研究结果支持了再结晶抗性淀粉在T2DM治疗中的潜在预防和治疗作用。
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