Probiotic and resveratrol normalize GLP-1 levels and oxidative stress in the intestine of diabetic rats

Abstract

Background: Recently, the use of incretins has been considered as a therapeutic target for diabetes. One of the important incretins in the improvement of diabetes is glucagon-like peptide (GLP-1), which is secreted by the gut and reduces the apoptosis of pancreatic β-cells and improves insulin sensitivity. In this experiment we determined the effects of resveratrol and probiotics on insulin resistance, oxidative stress, and GLP-1 in type 2 diabetes (T2D) rats.

Methods: In this study, 40 male Wistar male rats were divided into 5 groups: 1. Control group, 2. T2D, 3. T2D treated with probiotics, 4. T2D treated with resveratrol, 5. T2D group treated with probiotics and resveratrol. After four weeks, the intestine were removed for histopathological analysis, biochemical tests, and oxidative stress markers.

Results: Probiotics and resveratrol significantly decreased (p < 0.001) glucose and insulin resistance, and increased (p < 0.001) GLP1 and total antioxidant capacity compared to the diabetic group. Treatment with probiotics and resveratrol also returned intestinal histological changes in diabetic rats to normal.

Conclusion: Resveratrol and probiotics appear to be effective in controlling T2D by increasing GLP-1 levels and reducing oxidative stress.

Keywords: Glucagon-like peptide 1; Oxidative stress; Probiotics; Resveratrol; Type 2 diabetes.

Fig. 1

HOMA-B index in the study groups. Combination therapy normalized HOMA-B as compared with diabetic groups. Data are shown in Mean ± SD. D + Prob: Diabetic group received probiotic, D + RSV: Diabetic group received resveratrol, D + Prob + RSV: Diabetic group received probiotic and resveratrol. HOMA-B: Homeostasis model assessment B cell function. Prob: Probiotic, RSV: Resveratrol. ∗: compared with control groups, ¥: compared with diabetic animals, #a: compared with alone treatment resveratrol. #b: compared with alone treatment probiotic. ∗a: p < 0.001 compared to the control. ¥a: p < 0.001 compared with the diabetic.∗b: p < 0.01 compared with the control∗c: p < 0.05 compared with the control.

Fig. 2

GLP-1 levels in the intestine of study groups. Co-administration of probiotics and resveratrol led to a significant increase in GLP-1levels compared to the diabetic group. Data are shown in Mean ± SD. This increase was near healthy rats. D + Prob: Diabetic group received probiotic, D + RSV: Diabetic group received resveratrol, D + Prob + RSV: Diabetic group received probiotic and resveratrol. GLP-1: Glucagon-like peptide-1. Prob: Probiotic, RSV: Resveratrol. ∗: compared with control groups, ¥: compared with diabetic animals, #a: compared with alone treatment resveratrol. #b: compared with alone treatment probiotic. ∗a: p < 0.001 compared to the control. ∗c: p < 0.05 compared with the control. ¥c: p < 0.05 compared with the diabetic.

Fig. 3

TAC in the intestine of the study groups. Combination therapy led to a significant increase of TAC compared to the diabetic group. Data are shown in Mean ± SD. This increase was near healthy rats. D + Prob: Diabetic group received probiotic, D + RSV: Diabetic group received resveratrol, D + Prob + RSV: Diabetic group received probiotic and resveratrol. TAC: Total antioxidant capacity. Prob: Probiotic, RSV: Resveratrol. ∗: compared with control groups, ¥: compared with diabetic rats, #a: compared with alone treatment resveratrol. #b: compared with alone treatment probiotic. ∗a: p < 0.001 compared to the control. ∗b: p < 0.01 compared to the control. ¥b: p < 0.01 compared with the diabetic.¥c: p < 0.05 compared with the diabetic.

Fig. 4

TOS levels in the intestine of the study groups. Combination therapy led to a significant reduction of TOS compared to the diabetic group. This increase was near healthy rats. Control: Control group, Diabetic: Diabetic group, D + Prob: Diabetic group received probiotic, D + RSV: Diabetic group received resveratrol, D + Prob + RSV: Diabetic group received probiotic and resveratrol. TOS: Total oxidant status. Data are shown in Mean ± SD. Prob: Probiotic, RSV: Resveratrol. ∗: compared with control groups, ¥: compared with diabetic rats, #a: compared with alone treatment resveratrol. #b: compared with alone treatment probiotic. ∗c: p < 0.05 compared to the control. ¥c: p < 0.05 compared with the diabetic.

Fig. 5

Histological alteration in the intestine of different study groups. In diabetic rats, histological changes, include reduction in villi length, reduction in mucosal layer thickness, changes in epithelial cell arrangement, presence of mucosal lesions (lymph cell infiltration and vascular fragility) were observed in diabetic rats. Treatment with probiotics and resveratrol greatly improved intestinal morphological changes (magnification: ∗100). A: Control, B: Diabetic, C: Probiotic, D: Resveratrol and E: Combined group (Resveratrol + Probiotic, scale bar: 50 μm).