AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
PDF (8.4 MB)
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article | Open Access

Nuciferine relieves type 2 diabetes mellitus via enhancing GLUT4 expression and translocation

Tongxi ZhouaGuanjun SongbDi TianbQinghua LiubJinhua ShenbXinzhou Yanga( )Ping Zhaob( )
School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China
Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in the Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China

Peer review under responsibility of KeAi Communications Co., Ltd.

Show Author Information

Abstract

Nuciferine contained in lotus leaves have been confirmed to have the effect of ameliorating hyperlipemia and hyperglycemia. A laser scanning confocal microscope was used to track the translocation of glucose transporter 4 (GLUT4) in L6 cells and the changes in intracellular Ca2+ levels in real time, and related protease inhibitors combined with western blotting were used to explore the mechanism of nuciferine. Meanwhile, KK-Ay mice, the spontaneous type 2 diabetic mice, were used to evaluate the in vivo activity of nuciferine. In this study, the in vitro studies indicated that nuciferine-induced GLUT4 translocation was regulated by G protein-PLC-PKC and AMPK pathways and nuciferine-enhanced intracellular Ca2+ was mediated by G protein-PLC-IP3-IP3R pathway, the increase in intracellular Ca2+ caused by nuciferine was not directly related to GLUT4 translocation, but both promote glucose uptake. The in vivo results suggested that nuciferine ameliorated weight gain induced by high-fat diet, abnormal lipid metabolism and the symptoms of insulin resistance in KK-Ay diabetic mice. Western blot results suggested that nuciferine increased AMPK and PKC phosphorylation levels in skeletal muscle and liver, and enhanced GLUT4 expression in skeletal muscle. Taken together, this research showed that nuciferine has the non-negligible potential in the treatment of type 2 diabetes mellitus.

References

[1]

N.H. Cho, J.E. Shaw, S. Karuranga, et al., IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045, Diabetes Res. Clin. Pract. 138 (2018) 271-281. https://doi.org/10.1016/j.diabres.2018.02.023.

[2]

M. Reimann, E. Bonifacio, M. Solimena, et al., An update on preventive and regenerative therapies in diabetes mellitus, Pharmacol Ther. 121 (2009) 317-331. https://doi.org/10.1016/j.pharmthera.2008.11.009.

[3]

G.A. Nichols, T.M. Kimes, J.B. Harp, et al., Glycemic response and attainment of a1c goals following newly initiated insulin therapy for type 2 diabetes, Diabetes Care 35 (2012) 495-497. https://doi.org/10.2337/dc11-1171.

[4]

H.Y. Wang, X. Liu, H.F. Gan, et al., Genomic and biological characterization of a novel strain of sweet potato latent virus isolated from lotus (Nelumbo nucifera Gaertn.) J. Plant Pathology. 101 (2019) 1077-1084. https://doi.org/10.1007/s42161-019-00338-y.

[5]

Z. Lin, C. Zhang, D. Cao, et al., The Latest Studies on Lotus (Nelumbo nucifera)-an Emerging Horticultural Model Plant, Int J Mol Sci.Agr. 20 (2019) 36801. https://doi.org/10.3390/ijms20153680.

[6]

K.H. Nguyen, T.N. Ta, T.H. Pham, et al., Nuciferine stimulates insulin secretion from beta cells-an in vitro comparison with glibenclamide, J. Ethnopharmacol. 142 (2012) 488-495. https://doi.org/10.1016/j.jep.2012.05.024.

[7]

W.T. Garvey, L. Maianu, J.H. Zhu, et al., Multiple defects in the adipocyte glucose transport system cause cellular insulin resistance in gestational diabetes. heterogeneity in the number and a novel abnormality in subcellular localization of GLUT4 glucose transporters, Diabetes 42 (1993) 1773-1785. https://doi.org/10.2337/diab.42.12.1773.

[8]

W.T. Garvey, L. Maianu, J.H. Zhu, et al., Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance, J. Clin. Invest. 101 (1998) 2377-2386. https://doi.org/10.1172/JCI1557.

[9]

V.A. Lacombe, Expression and regulation of facilitative glucose transporters in equine insulin-sensitive tissue: from physiology to pathology, ISRN Vet. Sci. 2014 (2014) 409547. https://doi.org/10.1155/2014/409547.

[10]

M. Huang, P. Zhao, M. Xiong, et al., Antidiabetic activity of perylenequinonoid-rich extract from shiraia bambusicola in KK-AY mice with spontaneous type 2 diabetes mellitus, J. Ethnopharmacol. 191 (2016) 71-81. https://doi.org/10.1016/j.jep.2016.06.018.

[11]

P. Zhao, Q. Ming, M. Xiong, et al., Dandelion chloroform extract promotes glucose uptake via the AMPK/GLUT4 pathway in l6 cells, Evid Based Complement Alternat Med. 2018 (2018) 1709587. https://doi.org/10.1155/2018/1709587.

[12]

Y. Yao, F. Chen, M. Wang, et al., Antidiabetic activity of mung bean extracts in diabetic KK-AY mice, J. Agric. Food Chem. 56 (2008) 8869-8873. https://doi.org/10.1021/jf8009238.

[13]

C. Ma, G. Li, Y. He, et al., Pronuciferine and nuciferine inhibit lipogenesis in 3T3-L1 adipocytes by activating the AMPK signaling pathway, Life Sci. 136 (2015) 120-125. https://doi.org/10.1016/j.lfs.2015.07.001.

[14]

V. Ramachandran, R. Saravanan, Glucose uptake through translocation and activation of GLUT4 in PI3K/Akt signaling pathway by asiatic acid in diabetic rats, Hum. Exp. Toxicol. 34 (2015) 884-893. https://doi.org/10.1177/0960327114561663.

[15]

A. Tsuchiya, T. Kanno, T. Nishizaki, Diacylglycerol promotes GLUT4 translocation to the cell surface in a PKCε-dependent and PKCλ/ι and -ζ-independent manner, Life Sci. 93 (2013) 240-246. https://doi.org/10.1016/j.lfs.2013.06.014.

[16]

M. Diverse-Pierluissi, A.E. Remmers, R.R. Neubig, et al., Novel form of crosstalk between g protein and tyrosine kinase pathways, Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 5417-5421. https://doi.org/10.1073/pnas.94.10.5417.

[17]

J.P. Whitehead, J.C. Molero, S. Clark, et al., The role of Ca2+ in insulin-stimulated glucose transport in 3T3-L1 cells, J. Biol. Chem. 276 (2001) 27816-27824. https://doi.org/10.1074/jbc.M011590200.

[18]

C.H. Zhang, L.M. Lifshitz, K.F. Uy, et al., The cellular and molecular basis of bitter tastant-induced bronchodilation, PLoS Biol. 11 (2013) e1001501. https://doi.org/10.1371/journal.pbio.1001501.

[19]

F.S.A. Saadeldeen, Y. Niu, H. Wang, et al., Natural products: regulating glucose metabolism and improving insulin resistance, Food Sci. Human Well. 9 (2020) 214-228. https://doi.org/10.1016/j.fshw.2020.04.005.

[20]

C.J. Bailey, C. Day, Metformin: its botanical background, Practical Diabetes International. 21 (2004) 115-117. https://doi.org/10.1002/pdi.606.

[21]

X. Xu, F.S.A. Saadeldeen, L. Xu, et al., The mechanism of phillyrin from the leaves of forsythia suspensa for improving insulin resistance, Biomed. Res. Int. 2019 (2019) 3176483. https://doi.org/10.1155/2019/3176483.

[22]

L. Cui, J. Wang, M. Wang, et al., Chemical composition and glucose uptake effect on 3T3-L1 adipocytes of Ligustrum lucidum Ait. flowers, Food Sci. Human Well. 9 (2020) 124-129. https://doi.org/10.1016/j.fshw.2020.02.002.

[23]

M. Li, Z. Zhao, J. Xuan, et al., Research progress on chemical constituents and pharmacological effects of lotus leaf, J. Liaoning Univ. Tradit. Chin. Med. 22 (2020) 135-138. https://doi.org/10.13194/j.issn.1673-842x.2020.01.037.

[24]

Y. Yu, J. Lu, X.K. Lv, et al., Progress in pharmacology research and mechanisms of nuciferine, Modern Chinese Medicine 23 (2019) 1-14. https://doi.org/10.13313/j.issn.1673-4890.20191031002.

[25]

H. Xu, G.T. Barnes, Q. Yang, et al., Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance, J. Clin. Invest. 112 (2003) 1821-1830. https://doi.org/10.1172/JCI19451.

[26]

K. Srinivasan, P. Ramarao, Animal models in type 2 diabetes research: an overview, Indian J. Med. Res. 125 (2007) 451-472. https://doi.org/10.1111/j.1365-2567.2007.02591.x.

[27]

R. Weiss, S. Caprio, Obesity and T2DM in youth, Endocr Res. 33 (2008) 59-72. https://doi.org/10.1080/07435800802080211.

[28]

B.E. Vitola, S. Deivanayagam, R.I. Stein, et al., Weight loss reduces liver fat and improves hepatic and skeletal muscle insulin sensitivity in obese adolescents, Obesity (Silver Spring) 17 (2009) 1744-1748. https://doi.org/10.1038/oby.2009.171.

[29]

T. Hashimoto, W.S. Cook, C. Qi, et al., Defect in peroxisome proliferator-activated receptor alpha-inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting, J. Biol. Chem. 275 (2000) 28918-28928. https://doi.org/10.1074/jbc.M910350199.

[30]

J.K. Reddy, M.S. Rao, Lipid metabolism and liver inflammation, Ⅱ. fatty liver disease and fatty acid oxidation, Am. J. Physiol. Gastrointest Liver Physiol. 290 (2006) G852-G858. https://doi.org/10.1152/ajpgi.00521.2005.

[31]

E.R. Kallwitz, A. McLachlan, S.J. Cotler, Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease, World J. Gastroenterol. 14 (2008) 22-28. https://doi.org/10.3748/wjg.14.22.

[32]

B. Desvergne, L. Michalik, W. Wahli, Be fit or be sick: peroxisome proliferator-activated receptors are down the road, Mol. Endocrinol. 18 (2004) 1321-1332. https://doi.org/10.1210/me.2004-0088.

[33]

R.M. Evans, G.D. Barish, Y.X. Wang, Ppars and the complex journey to obesity, Nat. Med. 10 (2004) 355-361. https://doi.org/10.1038/nm1025

[34]

P. Tontonoz, B.M. Spiegelman, Fat and beyond: the diverse biology of PPARγ, Annu. Rev. Biochem. 77 (2008) 289-312. https://doi.org/10.1146/annurev.biochem.77.061307.091829.

[35]

S. Yu, K. Matsusue, P. Kashireddy, et al., Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor γ1 (PPARγ1) overexpression, J. Biol. Chem. 278 (2003) 498-505. https://doi.org/10.1074/jbc.M210062200.

[36]

E.D. Abel, O. Peroni, J.K. Kim, et al., Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver, Nature 409 (2001) 729-733. https://doi.org/10.1038/35055575.

[37]

A. Zisman, O.D. Peroni, E.D. Abel, et al., Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance, Nat. Med. 6 (2000) 924-928. https://doi.org/10.1038/78693.

[38]

Y. Li, L. Zheng, D. Wang, et al., Staurosporine as an agonist for induction of GLUT4 translocation, identified by a pH-sensitive fluorescent IRAP-mOrange2 probe, Biochem. Biophys. Res. Commun. 480 (2016) 534-538. https://doi.org/10.1016/j.bbrc.2016.10.056.

[39]

F.S. Thong, C.B. Dugani, A. Klip, Turning signals on and off: GLUT4 traffic in the insulin-signaling highway, Physiology (Bethesda) 20 (2005) 271-284. https://doi.org/10.1152/physiol.00017.2005.

[40]

Q. Li, X. Zhu, S. Ishikura, et al., Ca2+ signals promote GLUT4 exocytosis and reduce its endocytosis in muscle cells, Am. J. Physiol. Endocrinol. Metab. 307 (2014) E209-E224. https://doi.org/10.1152/ajpendo.00045.2014.

[41]

S.C. Lin, D.G. Hardie, AMPK: sensing glucose as well as cellular energy status, Cell Metab. 27 (2018) 299-313. https://doi.org/10.1016/j.cmet.2017.10.009.

[42]

B.B. Zhang, G. Zhou, C. Li, AMPK: an emerging drug target for diabetes and the metabolic syndrome, Cell Metab. 9 (2009) 407-416. https://doi.org/10.1016/j.cmet.2009.03.012.

[43]

D. Carling, C. Thornton, A. Woods, et al., AMP-activated protein kinase: new regulation, new roles?, Biochem. J. 445 (2012) 11-27. https://doi.org/10.1042/BJ20120546.

[44]

D. Leto, A.R. Saltiel, Regulation of glucose transport by insulin: traffic control of GLUT4, Nat. Rev. Mol. Cell Biol. 13 (2012) 383-396. https://doi.org/10.1038/nrm3351.

[45]

D.R. Park, K.H. Park, B.J. Kim, et al., Exercise ameliorates insulin resistance via Ca2+ signals distinct from those of insulin for GLUT4 translocation in skeletal muscles, Diabetes 64 (2015) 1224-1234. https://doi.org/10.2337/db14-0939.

[46]

N.B. Thillaiappan, P. Chakraborty, G. Hasan, et al., Ip3 receptors and Ca2+ entry, Biochim. Biophys. Acta Mol. Cell Res. 1866 (2019) 1092-1100. https://doi.org/10.1016/j.bbamcr.2018.11.007.

Food Science and Human Wellness
Pages 2040-2051
Cite this article:
Zhou T, Song G, Tian D, et al. Nuciferine relieves type 2 diabetes mellitus via enhancing GLUT4 expression and translocation. Food Science and Human Wellness, 2023, 12(6): 2040-2051. https://doi.org/10.1016/j.fshw.2023.03.020

726

Views

39

Downloads

3

Crossref

5

Web of Science

6

Scopus

0

CSCD

Altmetrics

Received: 08 May 2021
Revised: 27 May 2021
Accepted: 03 July 2021
Published: 04 April 2023
© 2023 Beijing Academy of Food Sciences.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Return