Whole-grain and moderately-milled quinoa regulate glucose metabolism via gut-liver axis in HFD/STZ-induced diabetic mice

• Effects of quinoa at different milling times on HFD/STZ induced T2D mice were investigated. • Whole grain and moderately-milled quinoa supplementation reduced the fasting glucose and HbA1c of T2D mice. • Whole grain and moderately-milled quinoa supplementation upregulated GLUT4 expression and downregulated GSY expression by the activation Akt signaling in T2D mice. • Muribaculaceae and Lactobacillus were distinguished bacteria in T2D fed with whole grain and moderately-milled quinoa. • Whole grain and moderately-milled quinoa supplementation increased fecal SCFAs in T2D mice. Milling is an essential processing step of cereal grains. How milling degree affects starch digestion has been investigated in vitro, yet its in vivo effects on glucose metabolism has rarely been reported. Quinoa were milled at different milling times (MTs) and were used to feed mice with type 2 diabetes (T2D). As the MTs increased, the fasting glucose, AUC of OGTT and HbA1c of T2D mice showed increasing trends. Whole-grain (MT0) and moderately-milled quinoa (MT20) upregulated GLUT4 expression, while downregulated GSY expression by activating hepatic Akt signaling. 16S rRNA sequencing revealed that Muribaculaceae and Lactobacillus were the distinguished bacteria in the MT0 and MT20 groups. This was associated with their higher fecal SCFAs. Higher MTs were positively correlated with glucose response and Desulfovibrionaceae , while negatively correlated with probiotics and SCFAs production. Results suggested that moderate milling might be an appropriate way to produce cereal grains with better texture and lower glucose response.