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

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.