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

ABSTRACT: 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 (p < 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 (p < 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 (p < 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 (p < 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.

SUBMITTER: Yang HJ

PROVIDER: S-EPMC8150986 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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

Yang Hye-Jeong HJ Zhang Ting T Wu Xuan-Gao XG Kim Min-Jung MJ Kim Young-Ho YH Yang Eun-Suk ES Yoon Yeong-Seok YS Park Sunmin S

Antioxidants (Basel, Switzerland) 20210510 5

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 ...[more]

PMID: 34068659

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Project description:: Silk fibroin hydrolysates have been reported to reduce hyperglycemia, but the mechanism has not been determined in Asian type 2 diabetes (T2DM). We hypothesized that the consumption of acid hydrolyzed silk peptides (SPs) alleviates hyperglycemia by improving insulin sensitivity and subsequently normalizing glucose-stimulated insulin secretion in T2DM. We investigated this hypothesis in a partial pancreatectomized (Px) rat model. Px rats was assigned randomly to the following six groups and fed assigned diet for 8 weeks: the Px-CON (0.5 g/kg/day dextrin), the SP-L (0.05 g/kg/day), the SP-M (0.1 g/kg/day), the SP-H (0.5 g/kg/day), the positive-CON (30 mg/kg/day metformin), or the normal-CON (sham-operated rats; 0.5 g/kg/day dextrin). SPs contained high levels of glycine, alanine, and serine. We found SPs dose-dependently increased food efficiency and body weight gain in Px rats. Animals in the Px-control group rats exhibited lower glucose metabolism, as evidenced by impaired glucose-stimulated insulin secretion coupled with impaired insulin sensitivity, and reduced bone mineral density (BMD) and lean body mass (LBM), compared to normal-CON. SPs and metformin similarly partially protected against Px-induced BMD loss in the lumbar spine and femur. Px-induced decreases in LBM were dose-dependently prevented by SPs, and muscle forces in the SP-M and SP-H groups were maintained at the normal-CON level. Glucose tolerance was dose-dependently improved by SPs as determined by oral glucose tolerance and oral maltose tolerance tests, and glucose tolerances were similar in the SP-H and positive-CON groups. Insulin tolerance, an index of insulin sensitivity, was dose-dependently enhanced by SPs, and the SP-H group exhibited better insulin tolerance than the positive-CON group as determined by intraperitoneal insulin sensitivity testing. Insulin secretory capacity assessed using a hyperglycemic clamp improved in the following order: Px-control <SA-L <SA-M <positive-control <SA-H <normal-control. SP-M prevented gut microbiota dysbiosis. In conclusion, SPs administered at 0.1-0.5 g/kg/day improved glucose regulation by potentiating both insulin secretion and insulin sensitivity in non-obese T2DM rats.

Project description:IntroductionIncrease in the prevalence of type-2 diabetes in Sub-Sahara Africa has created the need for robust treatment and management programs. However, an effective diabetes management program requires a high annual budget that most countries in this region cannot afford. That said, various plants and plant products in this region have either been confirmed and/or ethnopharmacologically used for the management of type-2 diabetes.AimTo investigate the antidiabetic and insulin secretory effects of an alkaloidal extract derived from Zanthoxylum zanthoxyloides in normoglycemic and experimental diabetic rats.Materials and methodsAlkaloidal extract was prepared from leaves of Z anthoxylum zanthoxyloides (ZZAE). Nicotinamide/streptozotocin-induced type-2 diabetes was modeled in male Sprague Dawley rats weighing between 130 to 150 g. The experimental diabetic rats were grouped into six treatment groups [Model, 20% Tween20, chlorpropamide, and ZZAE (50, 100, and 150 mg/kg)], and one control group. Fasting blood glucose (FBG), and body weight were measured weekly. Rats were sacrificed 2 days after treatment under chloroform anesthesia to collect blood samples and to isolate major organs for biochemical, and histological analyses respectively. Islets of Langerhans were isolated from normoglycemic rats and co-cultured with ZZAE and chlorpropamide (10 μg/mL) to assess the insulin secretory effect of ZZAE.ResultsZZAE improved glucose kinetics curve in normoglycemic (p < 0.001) and experimental diabetic rats (p < 0.05) compared to the model. ZZAE (100 and 150 mg/kg) restored islets population, and improved kidney, and liver, histoarchitecture. ZZAE (150 mg/kg) improved post-treatment serum insulin levels compared to the model group (p < 0.001) and the Chlorpropamide group (p < 0.05). ZZAE also restored glycogen synthesis in skeletal muscles of experimental diabetic rats and stimulated insulin secretion in pancreatic islets of Langerhans isolated from normoglycemic rats.ConclusionThese results showed that ZZAE has active alkaloids that can be explored for diabetes management.

Dataset Information

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

Publications

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

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