Anti-Diabetic Effects and Mechanisms of Dietary Polysaccharides
Abstract
:1. Introduction
2. Anti-Diabetic Potentials of Polysaccharides
3. Mechanism of Dietary Polysaccharides on Anti-Diabetic Activities
3.1. Hypoglycemic and Hypolipidemic Effects
3.2. Increasing β-Cell Mass and Reducing β-Cell Dysfunction
3.3. Antioxidant Effects
3.4. Anti-Cholesterolemic and Anti-Triglyceridemic Effects
3.5. Anti-Inflammatory Effects
3.6. Inhibition of α-Amylase and α-Glucosidase
3.7. Increasing Insulin Signaling Pathways
3.7.1. Activation of the PI3K/Akt Pathway
3.7.2. Modulation of the MAPK Pathway
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ACC | acetyl-CoA carboxylase |
ACE | angiotensin converting enzyme |
AGEs | advanced glycation end products |
Akt | serine/threonine-specific protein kinase |
ALP | alkaline phosphatase |
ALT | alanine transaminase |
AMPK | serine/threonine protein kinase |
AST | aspartate transaminase |
Bax | BCL2 associated X protein |
Bcl-2 | B-cell lymphoma 2 |
BUN | blood urea nitrogen |
CAT | catalase |
CPT1 | carnitine palmitoyltransferase-1 |
CRE | creatinine |
CVD | cardiovascular diseases |
CRP | c-reactive protein |
eNOS | endothelial nitric oxide synthase |
ERK | extracellular-signal-regulated kinase |
FBG | fasting blood glucose |
FFA | free fatty acids |
GLP-1 | glucagon-like peptide-1 |
GLUT4 | glucose transporter 4 |
GSH-Px | glutathione peroxidase |
GSH-R | glutathione reductase |
GSK- 3 | glycogen synthase kinase-3 |
HbA1c | glycated hemoglobin |
HDL-C | high-density lipoprotein –C |
HepG2 | human liver cancer cell line |
HFD | high-fat diet |
IF-γ | interferon γ |
IL | interleukin |
IL-6 | interleukin-6 |
InsR | insulin receptor |
IPITT | Intraperitoneal Insulin Tolerance Test |
IRS1 | Insulin receptor substrate 1 |
IRS-1,2 | insulin receptor-1,2 |
JNK | c-Jun N-terminal kinases |
K | potassium |
KDa | kilodaltons |
LDL-C | low-density lipoprotein -C |
LPO | lipid peroxidation |
LPS | lipopolysaccharides |
MAPK | mitogen-activated protein kinases |
MCP-1 | Monocyte chemoattractant protein-1 |
MDA | malondialdehyde |
mRNA | messenger RNA |
MTT | 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium |
Na | sodium |
NAG | n-acetyl-β-d-glucosaminidase |
NO | nitric oxide |
OGTT | oral glucose tolerance test |
OGTT | oral glucose tolerance test |
PBG | postprandial glucose |
PDX-1 | insulin promoter factor 1 |
PI3K | Phosphoinositide 3-kinases |
PK | pyruvate kinase |
PKC | protein kinase C |
PPAR-α | peroxisome proliferator-activated receptor-alpha |
PYY | peptide YY hormone |
SD | Sprague-Dawley |
SOD | superoxide dismutase |
SREBP-1c | sterol regulatory element binding protein -1c |
SREBP-2 | sterol regulatory element binding protein -2 |
STZ | streptozotocin |
T2DM | T2DM |
TC | total cholesterol |
TG | triglycerides |
TGF-β1 | transforming growth factor-β1 |
TNF-α | tumor necrosis factor-α |
UA | uric acid |
γGT | gamma-glutamyltransferase |
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Source of Polysaccharides | Botanical Name/Composition | Model | Doses and Route of Administration | Negative Control | Investigation | Results | References |
---|---|---|---|---|---|---|---|
Mushroom | Cordyceps militaris | Wistar mice | 100 and 400 mg/kg, p.o. for 4 weeks | STZ (60 mg/kg, i.p) | FBG, Serum Insulin, OGTT, AST, ALT, BUN, CRE, LDL-C, TC, HDL-C, hepatic, renal, and pancreatic SOD, GSH-Px, CAT, and lipid peroxidation | Antioxidant and hypoglycemic effects | [23] |
Mushroom | Cordyceps sinensis, Omphalia lapidescens, and Tricholomamongolicum | Wistar rats | 10 and 100 mg/kg, p.o. for 4 weeks | STZ (40 mg/kg, i.p) | FBG and PBG | Antioxidant and hypoglycemic effects | [24] |
Mushroom | Cordyceps sinensis, Omphalia lapidescens, and Tricholomamongolicum. | SD male rats | 500 mg and 2000 mg/kg, p.o. for 3 weeks | STZ (40 mg/kg, i.p) | FBG, PK, SOD, GSH-Px, TG, TC, BUN, UA, CRE, and urine protein levels | Anti-diabetic and anti-nephropathic activities | [25] |
Mushroom | Cordyceps militaris | Sprague-Dawley male rats | 0.5, 1.0, and 2.0 g/kg, p.o. for 4 weeks | STZ (40 mg/kg, i.p) | FBG, PK, SOD, GSH-Px, TG, TC, BUN, UA, CRE, urine protein, NAG, and MDA | Anti-diabetic and antinephritic activities | [26] |
Mushroom | Cordyceps mycelia | Male BALB/c mice and male Sprague-Dawley rats | 200 mg, 400 mg/kg, p.o. for 1-week | STZ (60 mg/kg, i.p), Alloxan monohydrate (150 mg/kg, i.p.) | Blood glucose and insulin | Hypoglycemic activity | [27] |
Mushroom | Cordyceps militaris | C57BL/6J mice | 360 mg/kg/p.o. for 8 weeks | HFD + STZ (60 mg/kg, i.p) + nicotinamide (180 mg/kg, i.p) | FBG, OGTT, IPITT, CRE, AGEs, TGF-β1, TC, TG, LDL-C, and HDL-C | Anti-diabetic and renoprotective activities | [28] |
Mushroom | Paecilomyces hepiali | Sprague-Dawley male rats | 0.08, 0.4, and 2.0 g/kg/p.o. for 4 weeks | HFD + STZ (25 mg/kg, i.p) + nicotinamide (180 mg/kg, i.p) | Blood glucose, TC, LDL-C, insulin, PK, glycogen, SOD, MDA, GSH-Px IL-2, IL-6, IL-10, and TNF-α | Anti-diabetic and antinephritic Activities | [29] |
Mushroom | Inonotus obliquus | HepG2 cells and insulin-resistant HepG2 cells | 10, 20, 40, 80, and 160 μg/mL, for 24 and 48 h. | - | Glucose, insulin | Hypoglycemic activity | [30] |
Mushroom | Antrodia cinnamomea | - | 50 μL | - | α-glucosidase inhibitory activity | Anti-diabetic activity | [31] |
Mushroom | Grifola frondosa | Male ICR mice, HepG2 | 75 and 150 mg/kg for 0, 14, and 28 days; 100 μg/mL | STZ (40 mg/kg, i.p) | Glucose, OGTT, insulin, IRS1, JNK1, PI3K, or GLUT4 | Anti-diabetic activity | [15,32] |
Mushroom | Aronia melanocarpa, red ginseng, and shiitake mushroom | Male SD rats | 0.5, 1 g/kg bw | Pancreatectomy rats with 1 g dextrin/kg bw | Serum glucose, food intake, body weight, and OGTT | Anti-diabetic activity | [33] |
Mushroom | Chroogomphus rutilus | Male SD rats | 1.0 and 2.0 g/kg bw, p.o. for 4 weeks | STZ (40 mg/kg, i.p) | α-glucosidase, blood glucose, SOD, GSH-Px, MDA, TC, TG, LDL-C, HDL-C, and MTT | Antioxidant, Hypoglycemic, Hypolipidemic, and Antitumor Activities | [34] |
Mushroom | Lignosus rhinocerotis | Male SD rats | 0.5, 1.0, and 2.0 g/kg bw, p.o. for 8 weeks | STZ (35 mg/kg, i.v.) | Blood glucose, GSH, CAT, SOD, and LPO | Anti-diabetic activity | [35] |
Mushroom | Agaricus brasiliensis and Ganoderma lucidum | Male SD rats | 1.0 and 2.0 g/kg bw, p.o. for 4 weeks | STZ (35 mg/kg, i.v.) | Blood glucose, GSH, CAT, SOD, LPO, TBARS, GSH-Px, and GSH-R | Anti-diabetic activity | [36] |
Mushroom | Pleurotus Ostreatus | KK-Ay Mice | 1.0 and 2.0 g/kg bw, p.o. for 4 weeks | STZ (35 mg/kg, i.v.) | Blood glucose, AMPK, GLUT-4, Akt, and PKC | Anti-diabetic activity | [37] |
Mushroom | Pleurotus Ostreatus | Rabbits | 100, 200, and 300 mg/kg for 4 weeks | Alloxan (120 mg/kg, p.o) | Blood glucose, ALP, γGT, ALT, AST, bilirubin, urea, BUN, CRE, Na, and K | Anti-diabetic activity | [38] |
Mushroom | Inonotus obliquus | Male Kunming mic | 900 mg/kg for 4 weeks | STZ (60 mg/kg, i.p.) | Blood glucose, body weight, organ weight, glycogen, OGTT, TC, TG, LDL-C, HDL-C, PI3K, GLUT-4, and Akt | Anti-diabetic activity | [39] |
Mushroom | Pleurotus citrinopileatus | In vitro | - | - | Pancreatic α-amylase, intestinal α-glucosidase, and ACE | Antioxidant, Hypoglycemic and Hypotensive Activities | [40] |
Mushroom | Catathelasma ventricosum | Male ICR mice | 0.2 g/kg for 4 weeks | STZ (150 mg/kg, i.p.) | Blood glucose, TC, TG, LDL-C, and HDL-C | Anti-diabetic activity | [41] |
Mushroom | Pleurotus ostreatus, Calocybe indica, and Volvariella volvacea | In vitro, in vivo (Male ICR mice) | 200 and 400 mg/kg for 6 weeks | STZ (150 mg/kg, i.p.) | α-amylase inhibition assay, glucose uptake by yeast cells, glucose adsorption capacity, and blood glucose | Anti-diabetic activity | [42] |
Mushroom | Pleurotus eryngii | KKAy mice | 1 g/kg for 6 weeks | STZ (150 mg/kg, i.p.) | Blood glucose, insulin, FBS, OGTT, TC, TG, LDL-C, HDL-C, liver glycogen | Hypolipidemic and hypoglycemic activities | [43] |
Grains | Foxtail Millet | Open-label, self-controlled clinical trial 64 subjects (27 male subjects and 37 female subjects) | 50–150 g of whole grain for week 6 and 12 | Diabetic patients | FBG, insulin, fructosamine, fasting C-peptide, TG, and TC HDL-C, LDL-C, apolipoprotein A1 and B, TNF-α, IL-6, leptin, GLP-1, blood pressure, body weight, waist circumference, and hip circumference | Anti-diabetic activity | [44] |
Vegetable, fruit, and grain | Vegetable, fruit, and grain | 48,835 post-menopausal women | A 1:1:0.5–serving/day vegetable, fruit, food grains | Diabetic patients | Serum glucose, insulin, and waist circumference | Reduced the risk of diabetes | [45] |
Whole Grain cereals | Whole grain cereals | A meta-analysis of randomized controlled trials | 50 g/day | Healthy Subjects | Serum glucose, insulin, and HbAlc | Improved the PBG and insulin homeostasis | [46] |
Grain and Sprouted grain | Grain and sprouted grain | 12 male subjects | 50 g/day | Healthy Subjects | Serum glucose, insulin, and HbAlc | Only sprouted-grain improved PBG and insulin | [47] |
Whole Grains muffins | Wheat, rice, corn, oat, and barley | 4 Male and 8 Female | 50 g/day | Healthy Subjects | Serum glucose, insulin, and HbAlc | Lowered the PBG | [48] |
Whole grains bread | Chickpea-wheat composite bread | 13 female subjects | 50 g/day | Healthy Subjects | Serum glucose, insulin, and HbAlc | Reduced PBG | [49] |
Whole grains bread | Maize | 30 male subjects | 50 g/day | Healthy Subjects | Serum glucose | Reduced PBG | [50] |
Sorghum and Wheat muffin | Sorghum and wheat flour | 10 male subjects | 50 g/day | Healthy Subjects | Serum glucose, insulin | Improved the PBG and insulin | [51] |
Whole rye bread | Whole rye with white wheat bread | 6 males and 9 females | 50 g/day | Healthy Subjects | Serum glucose, insulin | Improved the insulin response | [52] |
Oat | Oat | A meta-analysis of randomized controlled trials | 50 g/day | Healthy Subjects | Serum glucose, insulin | Improved glucose and insulin response | [53] |
Oat and beta-glucan | Oat and beta-glucan | A meta-analysis of randomized controlled trials | - | Healthy Subjects | Serum glucose, HbA1c, and insulin | Improved glucose and insulin and HbA1c response | [54] |
Whole grain rye with starch | Whole grain rye flour and rye kernels bread | 21 subjects | 50 g/day | Healthy Subjects | Serum glucose, OGTT, insulin, PYY, FFA, and IL-6 | Improved cardiometabolic variables and glucose | [55] |
Whole grain oats | Whole grain oats | A meta-analysis of randomized controlled trials | - | Healthy Subjects | Serum glucose, OGTT, insulin, and TC | Cholesterol-lowering and anti-diabetic effects | [56] |
Whole-grain rye and wheat bread | Whole-grain rye porridges and refined wheat bread | 21 subjects | 40, 55 g/day | Healthy Subjects | Serum glucose, postprandial plasma amino acids and short chain fatty acids | Suppressed appetite and improved glucose metabolism. | [57] |
Canola oil-enriched bread supplement | Canola oil-enriched bread | 141 subjects | 31 g/day | Diabetic patients | HbA1c, blood pressure, Framingham CVD risk score, and reactive hyperemia index ratio | Improved glycemic control in T2DM | [58] |
Grains | Monascus-fermented grains | Male SD rats | 300 mg/kg bw. For 16 weeks | High-fructose (60%, w/w) plus high-fat (20%, w/w) diet | OGTT, Insulin, insulin sensitivity index, TBARS, SOD, CAT, and GPx | Anti-diabetic effect by improving insulin resistance and hepatic antioxidant enzymes. | [59] |
Whole grains and legumes | Whole grains and legumes | 39 males, 146 females | 30–70 g for 16 weeks | Diabetic patients | BMI, waist and hip ratio, TC, TG, LDL-C, HDL-C, FBS, insulin FFA, Plasma apolipoprotein A-V, and CRP | Anti-diabetic effects | [60] |
DASH diet | fruits, vegetables, whole grains, low-fat dairy products, low in saturated fats, cholesterol, refined grains, and sweets | 52 pregnant women | 40 g for 4 weeks | Gestational Diabetic patients | Length, weight, and head circumference of infants | Improved gestational diabetes mellitus | [61] |
Whole grains | Cereal, bread, rice, pasta, and muffin | 11 subjects | 6–10 servings/day for 6 weeks | Diabetic/obese patients | Insulin, blood glucose, and OGTT | Reduce the risk of T2DM and heart disease. | [62] |
Vegetables | Okra (Abelmoschus esculentus L. Moench) | Male C57BL/6 mice | 50 mg/kg, p.o for 10 days | STZ (45 mg/kg, i.p.) | blood glucose, OGTT | Hypoglycemic effect | [63] |
Vegetables | Red pepper and soybeans | Male SD rats | 5% powder supplement | STZ (45 mg/kg, i.p.) | FBS, OGTT, body weight, visceral fat, and serum leptin | Improves glucose homeostasis by reducing insulin resistance | [64] |
Fruits and vegetables | Fruits and vegetables | 550 children and adolescents | 257, 227 g/day for 30 days | Diabetic patients | FBS, insulin, and HbA1c | Anti-diabetic effect | [50] |
Vegetables | Purple carrots and purple potatoes | Obese Zucker rats | Purple carrot and potatoes supplemented a high-fat diet for 8 weeks. | - | Intraperitoneal glucose and insulin tolerance test and invasive hemodynamic tests | Purple vegetables improve insulin resistance and hypertension | [65] |
Apricot Lychee | Prunus armeniaca Lychee chinensis | In vitro | - | - | α-glycosidase, aldose reductase, and antioxidant activity | Anti-diabetic effects | [66] |
Blueberry | Vaccinium cyanococcus | ||||||
Plum | Prunus salicina | ||||||
Kiwi | Kiwifruit c.v. hayward | ||||||
Lemon pulp | Citrus limon | ||||||
Lemon peel | Citrus limon | ||||||
Pear | Pyrus bretschneider | ||||||
Wolfberry | Lycium chinensis | ||||||
Watermelon | Citrullus lanatusus | ||||||
Lettuce | Lactuca sativa | In vitro | - | - | α-glycosidase, aldose reductase, and antioxidant activity | Anti-diabetic effects | [66] |
Cucumber | Cucumis sativus | ||||||
Red onion | Allium cepa | ||||||
Bitter gourd | Momordica charantia | ||||||
Eggplant | Solanum melongena | ||||||
Celery | Apium graveolens | ||||||
Kelp | Laminaria japonica | ||||||
Wax gourd | Benincasa pruriens | ||||||
Garlic | Allium sativum | ||||||
Tomato | Solanum lycopeersicum | ||||||
Vegetables | Momordica charantia | SD rats | 50 mg/kg, p.o for 10 days | STZ (45 mg/kg, i.p.) | FBS, insulin, and HbA1c | Anti-diabetic effects | [67] |
Sources of Polysaccharides | Monosaccharide Units/Active Compounds | Effects on Metabolism | Molecular Mechanisms | Results | References |
---|---|---|---|---|---|
Cyclocarya paliurus | Rhamnose, arabinose, xylose, mannose, glucose, and galactose | Triglyceride metabolism | ↑ATGL, ↑PPAR-α, ↑PPARɣ coactivator-1 α, ↓FAS, ↓HMG-CoA reductase | Anti-hyperlipidemic effects | [103] |
Cichorium intybus L. | Sorbin, glucose, fructose, and glucitol | Triglyceride metabolism | ↑p-AMPK, ↑ATGL, ↑CAPT1, ↑p-ACC, ↓FAS, | Anti-hyperlipidemic effects | [104] |
Lycium barbarum | Rhamnose, arabinose, xylose, mannose, glucose, galactose, and galacturonic acid | Triglyceride metabolism | ↑p-AMPK, ↑p-ACC, ↑ATGL, ↑CAPT1, ↓FAS | Anti-hyperlipidemic effects | [105] |
Enteromorpha prolifera | Rhamnose, glucuronic acid, arabinose, fucose, xylose, and glucose | Cholesterol metabolism | ↓SREBP-2, ↓HMG-CoA reductase | Cholesterol-lowering effects | [106] |
Oryza sativa L. | Xylose, rhamnose, mannose, galactose, arabinose, and glucose | Triglyceride and cholesterol metabolism | ↑PPAR-α, ↑PPARɣ coactivator-1 α, ↓SREBP-1c | Anti-hyperlipidemic effects | [107] |
Morchella angusticepes | Arabinose, mannose, glucose, and galactose | Cholesterol metabolism | ↓HMG-CoA reductase | Cholesterol-lowering effects | [109] |
Lentinula edodes | α- and β-glucans and fucomannogalactans | Cholesterol metabolism | ↓HMG-CoA reductase | Cholesterol-lowering effects | [110] |
Fucus vesiculosus | Sulfated polysaccharide with fucose | Triglycerides and cholesterol metabolism | ↓FAS, ↓ACC, ↓SREBP -1c, ↓SREBP-2, ↓HMG-CoA reductase | Triglyceride and Cholesterol-lowering effects | [111] |
Lycium barbarum | Rhamnose, arabinose, xylose, mannose, glucose, galactose, and galacturonic acid | Triglyceride and cholesterol metabolism | ↑p-AMPK, ↑PPARɣ coactivator-1 α, ↑p-ACC, ↓FAS, ↓SREBP-1c | Anti-hyperlipidemic effects | [116] |
Rheum palmatum L. | Rhamnose, mannose, and galactose | Triglyceride metabolism | ↑p-AMPK, ↑p-ACC | Anti-hyperlipidemic effects | [117] |
Schisandra Chinensis | Galactose, arabinose, and glucose | Triglyceride and cholesterol metabolism | ↓SREBP-1c, ↓SREBP-2, ↓FAS ↓ACC, ↓HMG-CoA reductase | Anti-hyperlipidemic effects | [118] |
Aconiti Lateralis Radix Praeparata | α-d-glucan | Cholesterol metabolism | ↑LDL receptor, ↓HMG-CoA reductase | Cholesterol-lowering effects | [119] |
Brasenia schreberi | Galactose, mannose, fucose, rhamnose, arabinose, xylose, glucose, and alduronic acids | Cholesterol metabolism | ↑LDL receptor, ↑PPAR-α | Cholesterol-lowering effects | [120] |
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Ganesan, K.; Xu, B. Anti-Diabetic Effects and Mechanisms of Dietary Polysaccharides. Molecules 2019, 24, 2556. https://doi.org/10.3390/molecules24142556
Ganesan K, Xu B. Anti-Diabetic Effects and Mechanisms of Dietary Polysaccharides. Molecules. 2019; 24(14):2556. https://doi.org/10.3390/molecules24142556
Chicago/Turabian StyleGanesan, Kumar, and Baojun Xu. 2019. "Anti-Diabetic Effects and Mechanisms of Dietary Polysaccharides" Molecules 24, no. 14: 2556. https://doi.org/10.3390/molecules24142556