Table 1.
Effects of resveratrol in diabetes.
| Study Type | Model | Dose/Dosing Method/Period | Outcome | Proposed Mechanism | Ref. |
|---|---|---|---|---|---|
| In vivo | SD rats (STZ DM model) | RES 0.5 mg/kg, gavage for 8–14 days | ↓Insulin resistance ↑Glucose uptake ↑Hepatic glycogen synthesis |
[14] | |
| In vivo | Wistar rats (STZ-NA model) | RES 5 mg/kg, oral for 30 days | ↓Blood glucose ↓Plasma insulin and hemoglobin ↓AST, ALT, ALP |
[15] | |
| In vivo | db/db mice (T2DM model) | RES (0.3% mixed in chow) for 8 weeks | ↑Mitochondrial oxidative stress and biogenesis ↓Blood glucose |
RES improves oxidative stress and promotes mitochondrial biogenesis through normal Mn-SOD function and glycolipid metabolism. | [16] |
| In vivo | C57BL/6 mice (HFD) | RES 0.03 µg/µL minipump Intracerebroventricularly, 14 weeks |
↓Hyperglycemia ↓Pyruvate-induced hyperglycemia |
RES improves hypothalamic NF-κB inflammatory signal transduction by decreasing total and acetylated RelA/P65 protein content. | [17] |
| In vivo | ob/ob mice (T2DM model) | RES 5, 15, 50 mg/kg, oral for 4 weeks | ↓Hyperglycemia ↓Insulin resistance ↓TG, TC, ADPN, FFA |
[18] | |
| In vivo | NOD mice (T1DM model) | RES 250 mg/kg oral or subcutaneously inject for 32 weeks | ↓Expression of inflammatory genes ↓Expression of CCR6 |
RES blocks CCR6 and CD11b (+) F4/80(hi) macrophages migration from peripheral lymphoid organs to the pancreas. | [19] |
| In vivo | C57BL/6 mice (HFD) | RES (0.04% mixed in chow) for 6 months | ↑Survival ↓Insulin sensitivity ↑Mitochondrial number |
RES reduces IGF-I levels and increases AMPK and PGC-1α activity. | [20] |
| In vivo | C57BL/6 mice (HFD) | RES 400 mg/kg, oral for 16 weeks | ↓Insulin resistance ↑Mitochondrial biogenesis ↑Oxidative phosphorylation |
RES improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. | [21] |
| In vivo | SD rats (HCF) | RES 1 mg/kg, oral for 15 days or 15 weeks | ↑Glucose uptake ↑Membrane trafficking activity of GLUT4 ↑Phosphorylation of insulin receptor |
ER is a key regulator in RES-stimulating insulin-dependent and -independent glucose uptake. | [22] |
| In vivo | Wistar rats (STZ/STZ-NA/ insulin-resistant diabetic model) | RES 3 or 10 mg/kg, oral for 90 min | ↓Blood glucose ↓Insulin resistance ↑GLUT4 expression |
RES promotes skeletal muscle glucose uptake through the PI3K-Akt signaling pathway. | [23] |
| In vivo | NOD mice (T1DM model) | RES 200 mg/kg, gavage for 28 days | ↓Blood glucose ↓Inflammatory factors |
RES improves renal function not only by its anti-inflammatory effect but also by improving the metabolic memory of hyperglycemia. | [24] |
| In vivo | SD rats (STZ model) | RES 5, 10 mg/kg, gavage for 1–7 months | ↓Blood glucose ↑Weight |
RES significantly inhibited the HG-induced decreases in glutamate uptake, GS activity, GLAST, and GS expression. | [25] |
| In vivo | Albino rats (Alloxan model) | RES 30 mg/kg, gavage for 30 days | ↓Hyperglycemia | [26] | |
| In vivo | ICR mice (HFD) | RES 50 mg/kg, oral for 10 days | ↓HIF-1α ↓Inflammation in the adipose tissue ↓Insulin sensitivity |
RES reduces cAMP accumulation by preserving PDE3B, thereby preventing PKA/HSL activation and lipolysis, and decreasing FFAs influx and DAG accumulation, thereby improving insulin signaling by inhibiting PKCθ translocation. | [27] |
| In vivo | Wistar rats (STZ model) | RES 5 mg/kg, oral for 8 weeks | ↓Blood glucose ↑Antioxidant status |
RES significantly improved the expression of TGF-β1, fibronectin, NF-κB/P65, Nrf2, Sirt1, and FoxO1 in the kidney. | [28] |
| In vivo | db/db, db/m mice (T2DM model) | RES 10 mg/kg, gavage for 12 weeks | ↓Apoptosis of podocytes ↑Autophagy of podocytes |
Resveratrol regulates autophagy and apoptosis of podocytes by inhibiting microRNA-383-5p. | [29] |
| In vivo | Wistar albino rats (STZ model) | RES 20 mg/kg, gavage for 8 weeks | ↓Hyperglycemia ↓Serum MDA concentrations |
Resveratrol inhibits oxidative stress and increases the potential of extra-hepatic tissues to absorb glucose. | [30] |
| In vivo | SD rats (HFS model) | RES 147.6 mg/kg, oral for 12 weeks | ↓Dysregulated gluconeogenesis ↓Dysregulation of several metabolic genes |
[31] | |
| In vivo | ICR mice (STZ model) | RES 50 mg/kg, oral for 7 days | ↓TXNIP/NLRP3 inflammasome activation ↓Cell apoptosis ↓ROS-associated mitochondrial fission |
Resveratrol inhibits Drp1 activity to protect mitochondrial integrity and inhibits endoplasmic reticulum stress to prevent NLRP3 inflammasome activation. | [32] |
ADPN: Adiponectin; AMPK: Adenosine 5-monophosphate (AMP)-activated protein kinase; ALP: Alkaline phosphatase; ALT: Alanine transaminase; AST: Aspartate transaminase; cAMP: Cyclic AMP; CCR6: Chemokine (C-C motif) ligand 6; DAG: Diacylglycerol; DM: Diabetes mellitus; Drp1: Dynamin-related protein 1; ER: Estrogen receptor; FFA: Free fatty acid; FoxO1: Forkhead transcription factor 1; GLAST: Glutamate transporters; GLUT4: Glucose transporter 4; GS: Glutamine synthetase; HCF: High cholesterol-fructose; HFS: High-fat and sucrose diet; HIF-1α: Hypoxia-inducible factor 1α; IGF-I: Insulin-like growth factor-1; MDA: Malondialdehyde; Mn-SOD: Manganese superoxide dismutase; NF-κB: Nuclear factor-kappaB; NLRP3: NOD-like receptor thermal protein domain associated protein 3; Nrf2: Nuclear factor E2-related factor; PDE3B: Phosphodiesterase 3B; PGC-1α: Peroxisome proliferator-activated receptor-gamma coactivator 1alpha; PI3K-Akt: phosphatidylinositol 3-kinase-Akt; PKCθ: Protein kinase Cθ; RES: Resveratrol; SIRT1: Sirtuin 1; STZ-NA: Streptozotocin and Nicotinamide; TC: Total cholesterol; TG: Triglycerides; TGF-β1: Transforming growth factor-beta1; TXNIP: Thioredoxin-interacting protein. ↑: Increase; ↓: Decrease.