Aqueous Blackcurrant Extract Improves Insulin Sensitivity and Secretion and Modulates the Gut Microbiome in Non-Obese Type 2 Diabetic Rats.

This study was undertaken to determine whether aqueous blackcurrant extracts (BC) improve glucose metabolism and gut microbiomes in non-obese type 2 diabetic animals fed a high-fat diet and to identify the mechanism involved. Partially pancreatectomized male Sprague-Dawley rats were provided a high-fat diet containing 0% (control), 0.2% (L-BC; low dosage), 0.6% (M-BC; medium dosage), and 1.8% (H-BC; high dosage) blackcurrant extracts; 0.2% metformin (positive-C); plus 1.8%, 1.6%, 1.2%, 0%, and 1.6% dextrin, specifically indigestible dextrin, daily for 8 weeks. Daily blackcurrant extract intakes were equivalent to 100, 300, and 900 mg/kg body weight (bw). After a 2 g glucose or maltose/kg bw challenge, serum glucose and insulin concentrations during peak and final states were obviously lower in the M-BC and H-BC groups than in the control group ( < 0.05). Intraperitoneal insulin tolerance testing showed that M-BC and H-BC improved insulin resistance. Hepatic triglyceride deposition, TNF-α expression, and malondialdehyde contents were lower in the M-BC and H-BC groups than in the control group. Improvements in insulin resistance in the M-BC and H-BC groups were associated with reduced inflammation and oxidative stress ( < 0.05). Hyperglycemic clamp testing showed that insulin secretion capacity increased in the acute phase (2 to 10 min) in the M-BC and H-BC groups and that insulin sensitivity in the hyperglycemic state was greater in these groups than in the control group ( < 0.05). Pancreatic β-cell mass was greater in the M-BC, H-BC, and positive-C groups than in the control group. Furthermore, β-cell proliferation appeared to be elevated and apoptosis was suppressed in these three groups ( < 0.05). Serum propionate and butyrate concentrations were higher in the M-BC and H-BC groups than in the control group. BC dose-dependently increased α-diversity of the gut microbiota and predicted the enhancement of oxidative phosphorylation-related microbiome genes and downregulation of carbohydrate digestion and absorption-related genes, as determined by PICRUSt2 analysis. In conclusion, BC enhanced insulin sensitivity and glucose-stimulated insulin secretion, which improved glucose homeostasis, and these improvements were associated with an incremental increase of the α-diversity of gut microbiota and suppressed inflammation and oxidative stress.