Table 1: Resveratrol and the Management of Diabetes – Cell Culture and Animal Studies.

Ref.	Model and Period	Parameters Analysed	Results and Conclusions
20	In vitro mouse 3T3–L1 adipocyte cell culture; in vivo male rhesus monkey; (2-year period)	Total cholesterol, LDL-C and HDL-C; protein extraction; Western blot and immunoprecipitation; gene expression; histology; immunocytochemistry; enzyme-linked immunosorbent assay; citrate synthase activity and hydrogen peroxide determination	↓ Adipocyte size, ↑ SIRT1 expression, ↓ NF-κB activation and improves insulin sensitivity in visceral WAT from HFS-fed animals
21	In vivo SD rats; STZ-induced type 2 diabetes model; dose 40 mg/kg IP; (24-week period)	Vascular permeability assay; histological examinations; immuno-histochemical staining; qRT-PCR analysis; Western blot analysis; cell culture and viability assay; inhibition of NF-κB p65 activation by small interfering RNA and PDTC in cultured endothelial cells	↓ NF-κB, ↓ IL-1β and ↓ IL-6 in blood; ↓ TNFα, ↓ ICAM-1 and ↓ MCP-1 expressions in vascular wall
22	In vitro RINm5F pancreatic cells from MG-induced apoptosis	ROS measurement; assay for cell apoptosis; Western immuno blotting; detection of insulin protein expression in RINm5F cells	Inhibits MG-mediated expression of CCAAT/enhancer-binding protein C/EBP-β activates the expression of Nrf2
23	In vitro cell culture-3T3-LI pre-adipocytes; in vivo C57BL/6J female mice; diet regulation; (6-week period)	Oil red O staining; RT-PCR; glucose uptake into C2C12 cells; Western blot analysis; oral GTT; ITT; measurement of glucose uptake into skeletal muscle	Inhibits adipocyte differentiation, ↑ glucose uptake in the myotubes
24	In vivo male, 5-week-old db/db and db/dm (non-diabetic control) mice (12-week period)	GTT and ITT; immunohistochemical staining; Masson’s trichrome staining; beta-cell mass in pancreatic islet; plasma and urinary ROS markers	Improves glucose tolerance at 2 hours in db/db mice; ↑ pancreas weight and beta-cell mass; ↓ islet fibrosis and urinary 8-OHdG levels
25	In vivo male C57BL/6J mice; (24-week period)	Isolation and batch incubation of islets, morpho metric evaluation; pancreatic insulin content; apoptosis by TUNEL TG measurements in pancreas; RT-PCR; IPGTTs; analysis of protein expression by Western blot analysis; oxidative stress damage	↓ The levels of glucose, ↓ lipid metabolism, ↓ beta cell mass, ↓ lipid content, ↓ oxidative stress; promotes SIRT1 expression islets; beneficial effect on the ratios of expressions of Bcl-2/Bax and levels of malondialdehyde/↑ glutathione peroxidase
26	In vitro mesangial cells-glomeruli of SD rats	SIRT1 activity assessment; Western blot analysis; intracellular ROS assay; mitochondrial superoxide generation determination; MnSOD activity assay; determination of activities of mitochondrial complexes I and III; measurement of mitochondrial membrane potential; ATP content determination; MtDNA content detection	↓ Hyperglycaemia-induced increase in ROS production and mitochondrial superoxide generation and stimulates MnSOD activity; reverses the mitochondrial complex III activity and restores the hyperpolarisation of Δφm, ↑ ATP production and preserve the mtDNA content
27	In vivo STZ-induced model; male wistar rats; dose 55 mg/kg IP; (30-day period)	Blood glucose and body weight; determination of lipid peroxidation; CAT and SOD activities; vitamin C NPSH content; δ-ALA-D; biochemical analysis; protein determination	Prevents the ↑ CAT, ↑ SOD and ↑ δ-ALA-D and the levels of nonprotein thiols and vitamin C; ↓ serum ALT, ↓ AST and ↓ rGT activities, ↓ levels of urea, ↓ creatinine, ↓ cholesterol and triglycerides (to normal levels)
28	In vitro cell culture THP-1 cell line	Trypan blue exclusion assay; immunostaining; preparation of nuclear fraction; measurement of HDAC activity using ELISA; Western blot analysis; measurement of intracellular superoxide production; small interfering RNA transfection assays	↓ HG-induced superoxide production via upregulation of SIRT1, induction of FOXO3a and inhibition of p47phox in monocytes
29	In vivo male SD rats; STZ-induced model (8-week period)	Plasma biochemistry; isolation of glomeruli; assessment of kidney morphology and estimation of glomerular volume by light microscopy; immunohistochemical staining for TGF-β1, fibronectin and collagen IV in glomeruli; Western blot analysis; electron microscopy	Urinary albumin excretion, glomerular hypertrophy and expressions of fibronectin, collagen IV and TGF-β in the glomeruli were alleviated; ↓ the thickness of the glomerular basement membrane to the original thickness; ↑ Increases nephrin expressions to normal levels; Inhibits phosphorylation of smad2, smad3 and ERK1/2 in diabetic rat kidneys

8-OHdG = 8-hydroxy-2’-deoxyguanosine; ALT = alanine aminotransferase; AST = aspartate aminotransferase; ATP = adenosine triphosphate; CAT = catalase; δ-ALA-D = delta-aminolevulinic acid dehydratase; ELISA = enzyme linked immunosorbent assay; ERK1/2 = extracellular signal-regulated protein kinases 1/2; GTT = glucose tolerance test; HDAC = histone deacetylase; HDL-C = high-density lipoprotein cholesterol; HFS = high fat sucrose; HG = high glucose; ICAM-1 = intercellular adhesion molecule-1; IL = interleukin; IPGTT = intraperitoneal glucose tolerance test; IP = intraperitoneal; ITT = insulin tolerance test; IV = intravenous; LDL-C = low-density lipoprotein cholesterol; MCP-1 = monocyte chemoattractant protein 1; MG = methylglyoxal; MnSOD = manganese superoxide dismutase; MtDNA = mitochondrial DNA; NF-κB = nuclear factor kappaB; NPSH = non protein thiol; PDTC = pyrrolidine dithiocarbamate; qRT-PCR = quantitative reverse transcription polymerase chain reaction; rGT = r-glutamyltranspeptidase; SD = Sprague Dawley; RNA = ribonucleic acid; ROS = reactive oxidative stress; RT = real time; SIRT1 = sirtuin 1; SOD = superoxide dismutase; STZ = streptozotocin; TG = triglyceride; TGF-β1 = transforming growth factor beta 1; TNFα = tumour necrosis factor-alpha; TUNEL = terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; WAT = white adipose tissue.