Type 2 diabetes mellitus (T2DM) is a metabolic disease caused by a glycolipid metabolism disorder and islet β-cell dysfunction. SCP-80-I is a biologically active water-soluble polysaccharide isolated from sweet corncob, an agricultural byproduct. The hypoglycemic effects of SCP-80-I on T2DM mice and its mechanisms were investigated in this study. SCP-80-I was found to significantly reduce blood glucose and lipid deposition levels in T2DM mice, as well as decrease serum leptin and increase adiponectin secretion. Interestingly, real time-polymerase chain reaction (RT-PCR) and Western blotting results revealed that SCP-80-I could regulate the expression of several glycolipid metabolisms and insulin secretion genes and proteins, including 5’-AMP-activated protein kinase (AMPK), carnitine palmitoyltransferase I (CPT1), and acetyl coenzyme A carboxylase (ACC) in the liver and AMPK, sirtuin 1 (Sirt1), peroxisome proliferator-activated receptorycoactivator-1 (PGC-1α), and uncoupling protein 2 (UCP2) in the pancreas. To have a hypoglycemic effect, SCP-80-I regulated glycolipid metabolism and islet cell function in the liver by regulating the AMPK/ACC/CPT1 signaling pathway and the AMPK/Sirt1/PGC-1α and AMPK/Sirt1/UCP2 signaling pathways. These findings improve our understanding of polysaccharides derived from sweet corncob and the use of SCP-80-I in the production of hypoglycemic foods.
K. Kalliopi, M. Yannis, The role of lifestyle, eating habits and social environment in the prevention and treatment of type 2 diabetes and hypertension, Nutrients 13(5) (2021) 1460. https://doi.org/10.3390/NU13051460.
C. Hu, W. Jia, Diabetes in China: epidemiology and genetic risk factors and their clinical utility in personalized medication, Diabetes 67(1) (2018) 3-11. https://doi.org/10.2337/dbi17-0013.
G. Marta, H. Adela, T. Estefanía, et al., Metabolomics in prediabetes and diabetes: a systematic review and meta-analysis, Diabetes Care 39(5) (2016) 833-846. https://doi.org/10.2337/dc15-2251.
J. Marín-Peñalver, I. Martín-Timón, C. Sevillano-Collantes, et al., Update on the treatment of type 2 diabetes mellitus, World J. Diabetes 7(17) (2016) 354. https://doi.org/10.4239/wjd.v7.i17.35.
E. Stuermer, B. Klara, N. Terberger, et al., Side effects of frequently used oral antidiabetics on wound healing in vitro, Naunyn-Schmiedeberg’s Arch. Pharmacol. 392(3) (2019) 371-380. https://doi.org/10.1007/s00210-018-01597-9.
H. David, S. Alan, K. Andrew, Effects of glucose-lowering drugs on body weight in type 2 diabetes, Prescriber 22(19) (2011) 32-42. https://doi.org/10.1002/psb.810.
H. Wang, Q. Li, N. Yu, et al., Dendrobium huoshanense polysaccharide regulates hepatic glucose homeostasis and pancreatic β-cell function in type 2 diabetic mice, Carbohydr. Polym. 211 (2019) 39-48. https://doi.org/10.1016/j.carbpol.2019.01.101.
C. Zhang, H. Chen, W. Bai, Characterization of Momordica charantia L. polysaccharide and its protective effect on pancreatic cells injury in STZ-induced diabetic mice, Int. J. Biol. Macromol. 115 (2018) 45-52. https://doi.org/10.1016/j.ijbiomac.2018.04.039.
Y. Zhang, C. Ren, G. Lu, et al., Purification, characterization and anti-diabetic activity of a polysaccharide from mulberry leaf, Regul. Toxicol. Pharmacol. 70(3) (2014) 687-695. https://doi.org/10.1016/j.yrtph.2014.10.006.
R. Jia, Z. Li, Z. Ou, et al., Physicochemical characterization of Hizikia fusiforme polysaccharide and its hypoglycemic activity via mediating insulin-stimulated blood glucose utilization of skeletal muscle in type 2 diabetic rats, Chem. Biodiversity 17(10) (2020) e2000367. https://doi.org/10.1002/cbdv.202000367.
Z. Wang, Z. Wang, W. Huang, et al., Antioxidant and anti-inflammatory activities of an anti-diabetic polysaccharide extracted from Gynostemma pentaphyllum herb, Int. J. Biol. Macromol. 145(C) (2020) 484-491. https://doi.org/10.1016/j.ijbiomac.2019.12.213.
H. Zhao, Q. Lai, J. Zhang, et al., Antioxidant and hypoglycemic effects of acidic-extractable polysaccharides from Cordyceps militaris on type 2 diabetes mice, Oxid. Med. Cell. Longevity 2018 (2018) 9150807. https://doi.org/10.1155/2018/9150807.
J. Li, M. Luo, Z. Luo, et al., Transcriptome profiling reveals the anti-diabetic molecular mechanism of Cyclocarya paliurus polysaccharides, J. Funct. Foods 55 (2019) 1-8. https://doi.org/10.1016/j.jff.2018.12.039.
F. Yu, Y. Wang, Y. Teng, et al., Interaction and inhibition of a Ganoderma lucidum proteoglycan on PTP1B activity for anti-diabetes, ACS Omega 6(44) (2021) 29804-29813. https://doi.org/10.1021/ACSOMEGA.1C04244.
P. Gong, D. Cui, Y. Guo, et al. A novel polysaccharide obtained from Siraitia grosvenorii alleviates inflammatory responses in a diabetic nephropathy mouse model via the TLR4-NF-κB pathway, Food Funct. 12(19) (2021) 9054-9065. https://doi.org/10.1039/D1FO01182K.
X. Wang, Z. Wang, K. Zhang, et al., Effects of sweet corncob polysaccharide on pancreatic protein expression in type 2 diabetic rats, J. Funct. Foods 88 (2022) 104908. https://doi.org/10.1016/J.JFF.2021.104908.
Z. Wang, X. Wang, W. Xiu, et al., Characteristics of selenium polysaccharide from sweet corncob and its effects on non-enzymatic glycosylation in vivo, Appl. Biol. Chem. 65(1) (2022) 1-15. https://doi.org/10.1186/s13765-022-00678-x.
X. Xu, C. Fang, Y. Wang, et al., Integrating network pharmacology and metabolomics to elucidate the mechanism of action of Huang Qin decoction for treament of diabetic liver injury, Front. Pharmacol. 13 (2022) 899043. https://doi.org/10.3389/FPHAR.2022.899043.
Z. Li, R. Jia, D. Luo, et al., The positive effects and underlying mechanisms of Undaria pinnatifida polysaccharides on type 2 diabetes mellitus in rats, Food Funct. 12 (2021) 11898-11912. https://doi.org/10.1039/d1fo01838.
P. Suthamwong, M. Minami, T. Okada, et al., Administration of mulberry leaves maintains pancreatic β-cell mass in obese/type 2 diabetes mellitus mouse model, BMC Complement. Med. Ther. 20(1) (2020) 136. https://doi.org/10.1186/s12906-020-02933-4.
S. Shivani, S. Priya, P. Harsh, et al., Incretin hormones receptor signaling plays the key role in antidiabetic potential of PTY-2 against STZ-induced pancreatitis, Biomed. Pharmacother. 97 (2018) 330-338. https://doi.org/10.1016/j.biopha.2017.10.071.
P. Zhao, Q. Ming, J. Qiu, et al., Ethanolic extract of folium sennae mediates the glucose uptake of L6 cells by GLUT4 and Ca2+, Molecules 23(11) (2018) 2934. https://doi.org/10.3390/molecules23112934.
Q. Guo, Z. Chen, R. Santhanam, et al., Hypoglycemic effects of polysaccharides from corn silk (Maydis stigma) and their beneficial roles via regulating the PI3K/Akt signaling pathway in L6 skeletal muscle myotubes, Int. J. Biol. Macromol. 121 (2018) 981-988. https://doi.org/10.1016/j.ijbiomac.2018.10.100.
Z. Bai, J. Meng, X. Huang, et al., Comparative study on antidiabetic function of six legume crude polysaccharides, Int. J. Biol. Macromol. 154(C) (2020) 25-30. https://doi.org/10.1016/j.ijbiomac.2020.03.072.
M. Ivan, V. Rafael, A. Irene, et al., Amylin as a potential link between type 2 diabetes and alzheimer disease, Ann. Neurol. 86(4) (2019) 539-551. https://doi.org/10.1002/ana.25570.
Y. Yin, Z. Zheng, Z. Jiang. Effects of lycopene on metabolism of glycolipid in type 2 diabetic rats, Biomed. Pharmacother. 109 (2019) 2070-2077. https://doi.org/10.1016/j.biopha.2018.07.100.
Y. Li, D. Chen, C. Xu, et al., Glycolipid metabolism and liver transcriptomic analysis of the therapeutic effects of pressed degreased walnut meal extracts on type 2 diabetes mellitus rats, Food Funct. 11(6) (2020) 5538-5552. https://doi.org/10.1039/d0fo00670j.
R. Wang, L. Zhang, Q. Zhang, et al., Glycolipid metabolism and metagenomic analysis of the therapeutic effect of a phenolics-rich extract from noni fruit on type 2 diabetic mice, J. Agric. Food Chem. 70 (2022) 2876-2888. https://doi.org/10.1021/acs.jafc.1c07441.
H. Balandrano, C. Zhi, H. Ruth, et al., Hypoglycemic and hypolipidemic effects of blueberry anthocyanins by AMPK activation: in vitro and in vivo studies, Redox Biol. 46 (2021) 102100. https://doi.org/10.1016/j.redox.2021.102100.
Y. Zhou, N. Xu, X. Zhang, et al., Chrysin improves glucose and lipid metabolism disorders by regulating the AMPK/PI3K/AKT signaling pathway in insulin-resistant HepG2 cells and HFD/STZ-induced C57BL/6J mice, J. Agric. Food Chem. 20 (2021) 69. https://doi.org/10.1021/ACS.JAFC.1C01109.
M. Wang, H. Ma, S. Guan, et al., Astaxanthin from Haematococcus pluvialis alleviates obesity by modulating lipid metabolism and gut microbiota in mice fed a high-fat diet, Food Funct. 12(20) (2021) 9719-9738. https://doi.org/10.1039/D1FO01495A.
W. Lin, Y. Jin, X. Hu, et al., AMPK/PGC-1α/GLUT4-mediated effect of icariin on hyperlipidemia-induced non-alcoholic fatty liver disease and lipid metabolism disorder in mice, Biochemistry (Moscow) 86(11) (2021) 1407-1417. https://doi.org/10.1134/S0006297921110055.
Y. Wu, F. Zhou, H. Jiang, et al., Chicory (Cichorium intybus L.) polysaccharides attenuate high-fat diet induced non-alcoholic fatty liver disease via AMPK activation, Int. J. Biol. Macromol. 118 (2018) 886-895. https://doi.org/10.1016/j.ijbiomac.2018.06.140.
N. Xu, Y. Zhou, X. Lu, et al., Auricularia auricula-judae (Bull.) polysaccharides improve type 2 diabetes in HFD/STZ-induced mice by regulating the AKT/AMPK signaling pathways and the gut microbiota, J. Food Sci. 86(12) (2021) 5479-5494. https://doi.org/10.1111/1750-3841.15963.
F. Zhao, K. Zhu, Q. Zhao, et al., Holothuria leucospilota polysaccharides alleviate liver injury via AMPK and NF-κB signaling pathways in type 2 diabetic rats, J. Funct. Foods 85 (2021) 104657. https://doi.org/10.1016/J.JFF.2021.104657.
L. Wang, C. Li, Q. Huang, et al., Polysaccharide from Rosa roxburghii Tratt fruit attenuates hyperglycemia and hyperlipidemia and regulates colon microbiota in diabetic db/db mice, J. Agric. Food Chem. 68(1) (2020) 147-159. https://doi.org/10.1021/acs.jafc.9b06247.
R. Ren, J. Gong, Y. Zhao, et al., Sulfated polysaccharide from Enteromorpha prolifera suppresses SREBP-1c and ACC expression to lower serum triglycerides in high-fat diet-induced hyperlipidaemic rats, J. Funct. Foods 40 (2018) 722-728. https://doi.org/10.1016/j.jff.2017.12.010.
P. Li, Z. Xia, W. Kong, et al., Exogenous L-carnitine ameliorates burn-induced cellular and mitochondrial injury of hepatocytes by restoring CPT1 activity, Nutr. Metab. 18(1) (2021) 65-65. https://doi.org/10.1186/S12986-021-00592-X.
L. Dong, X. Han, X. Tao, et al., Protection by the total flavonoids from Rosa laevigata Michx fruit against lipopolysaccharide-induced liver injury in mice via modulation of FXR signaling, Foods 7(6) (2018) 88-88. https://doi.org/10.3390/foods7060088.
S. Zhao, S. Zhang, W. Zhang, et al., First demonstration of protective effects of purified mushroom polysaccharide-peptides against fatty liver injury and the mechanisms involved, Sci. Rep. 9(1) (2019) 13725. https://doi.org/10.1038/s41598-019-49925-0.
M. Xin, Y. Sun, H. Chen, et al., Propylene glycol guluronate sulfate (PGGS) reduces lipid accumulation via AMP-activated kinase activation in palmitate-induced HepG2 cells, Int. J. Biol. Macromol. 114 (2018) 26-34. https://doi.org/10.1016/j.ijbiomac.2018.03.068.
L. Carneiro, M. Asrih, C. Repond, et al., AMPK activation caused by reduced liver lactate metabolism protects against hepatic steatosis in MCT1 haploinsufficient mice, Mol. Metab. 6(12) (2017) 1625-1633. https://doi.org/10.1016/j.molmet.2017.10.005.
Q. Li, X. Lai, L. Sun, et al., Antiobesity and anti-inflammation effects of Hakka stir-fried tea of different storage years on high-fat diet-induced obese mice model via activating the AMPK/ACC/CPT1 pathway, Food Nutr. Res. 64 (2020) 1681. https://doi.org/10.29219/fnr.v64.1681.
Y. Zhang, Z. He, X. Liu, et al., Oral administration of Angelica sinensis polysaccharide protects against pancreatic islets failure in type 2 diabetic mice: pancreatic β-cell apoptosis inhibition, J. Funct. Foods 54 (2019) 361-370. https://doi.org/10.1016/j.jff.2019.01.037.
S. Xu, Y. Dou, B. Ye, et al., Ganoderma lucidum polysaccharides improve insulin sensitivity by regulating inflammatory cytokines and gut microbiota composition in mice, J. Funct. Foods 38 (2017) 545-552. https://doi.org/10.1016/j.jff.2017.09.032.
A. Sulaimon, O. Tosin, I. Boyenle, et al., AMPK allostery: a therapeutic target for the management/treatment of diabetic nephropathy, Life Sci. 261 (2020) 118455. https://doi.org/10.1016/j.lfs.2020.118455.
J. Xu, S. Wang, T. Feng, et al., Hypoglycemic and hypolipidemic effects of total saponins from Stauntonia chinensis in diabetic db/db mice, J. Cell. Mol. Med. 22(12) (2018) 6026-6038. https://doi.org/10.1111/jcmm.13876.
T. Szkudelski, K. Szkudelska, The relevance of AMP-activated protein kinase in insulin-secreting β cells: a potential target for improving β cell function, J. Physiol. Biochem. 75(4) (2019) 423-432. https://doi.org/10.1007/s13105-019-00706-3.
N. Wang, Z. Ma, C. Chen, et al., Effects of maslinic acid on cardiac function in ischemia-reperfusion injury rats, J. Invest. Med. 70(1) (2021) 20-28. https://doi.org/10.1136/JIM-2021-001927.
S. Lu, S. Zhou, J. Chen, et al., Quercetin nanoparticle ameliorates lipopolysaccharide-triggered renal inflammatory impairment by regulation of Sirt1/NF-κB pathway, J. Biomed. Nanotechnol 17(2) (2021) 230-241. https://doi.org/10.1166/JBN.2021.3031.
X. Duan, W. Sun, H. Sun, et al., Perfluorooctane sulfonate continual exposure impairs glucose-stimulated insulin secretion via Sirt1-induced upregulation of UCP2 expression, Environ. Pollut. 278 (2021) 116840. https://doi.org/10.1016/J.ENVPOL.2021.116840.
A. Mihanfar, M. Akbarzadeh, D. Ghazizadeh, et al., Sirt1: a promising therapeutic target in type 2 diabetes mellitus, Arch. Physiol. Biochem. (2021) 11-16. https://doi.org/10.1080/13813455.2021.1956976.
A. Dierendonck, S. Tiphaine, A. Marie-Clotilde, et al., The role of uncoupling protein 2 in macrophages and its impact on obesity-induced adipose tissue inflammation and insulin resistance, J. Biol. Chem. 295(51) (2020) 17535-17548. https://doi.org/10.1074/jbc.ra120.014868.
H. Li, D. Chen, W. Sun, et al., KATP opener attenuates diabetic-induced Müller Gliosis and inflammation by modulating Kir6.1 in Microglia, Invest. Ophthalmol. Visual Sci. 62(2) (2021) 3. https://doi.org/10.1167/IOVS.62.2.3.
S. Nivedita, E. Michael, L. Kristin, et al., Uncoupling protein 2 regulates daily rhythms of insulin secretion capacity in MIN6 cells and isolated islets from male mice, Mol. Metab. 6(7) (2017) 760-769. https://doi.org/10.1016/j.molmet.2017.04.008.
E. Haythorne, M. Rohm, M. Bunt, et al., Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells, Nat. Commun. 10(1) (2019) 1-17. https://doi.org/10.1038/s41467-019-10189-x.
G. Rutter, E. Georgiadou, A. Martinez-Sanchez, et al., Metabolic and functional specialisations of the pancreatic beta cell: gene disallowance, mitochondrial metabolism and intercellular connectivity, Diabetologia 63(10) (2020) 1990-1998. https://doi.org/10.1007/s00125-020-05205-5.
M. Masini, L. Martino, L. Marselli, et al., Ultrastructural alterations of pancreatic beta cells in human diabetes mellitus, Diabetes/Metab. Res. Rev. 33(6) (2017) e2894. https://doi.org/10.1002/dmrr.2894.
N. Sawada, A. Jiang, F. Takizawa, et al., Endothelial PGC-1α mediates vascular dysfunction in diabetes, Cell Metab. 19(2) (2014) 246-258. https://doi.org/10.1016/j.cmet.2013.12.014.
X. Wang, H. Gao, W. Wu, et al., The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1-and PGC-1α-mediated regulation of Glut2, Protein Cell 10(6) (2019) 436-449. https://doi.org/10.1007/s13238-018-0580-1.
S. Rius-Pérez, I. Torres-Cuevas, I. Millán, et al., PGC-10, inflammation, and oxidative stress: an integrative view in metabolism, Oxid. Med. Cell. Longevity 2020 (2020). https://doi.org/10.1155/2020/1452696.
Y. Zhu, H. Yang, J. Deng, et al., Ginsenoside Rg5 improves insulin resistance and mitochondrial biogenesis of liver via regulation of the Sirt1/PGC-1α signaling pathway in db/db mice, J. Agric. Food Chem. 69(30) (2021) 8428-8439. https://doi.org/10.1021/acs.jafc.1c02476.
H. Qian, Y. Li, L. Wang, Vaccinium bracteatum Thunb. leaves’ polysaccharide alleviates hepatic gluconeogenesis via the downregulation of miR-137, Biomed. Pharmacother. 95 (2017) 1397-1403. https://doi.org/10.1016/j.biopha.2017.09.040.
R. Zhang, X. Qin, T. Zhang, et al., Astragalus polysaccharide improves insulin sensitivity via AMPK activation in 3T3-L1 adipocytes, Molecules 23(10) (2018) 2711-2711. https://doi.org/10.3390/molecules23102711.