Effects of L-arabinose by hypoglycemic and modulating gut microbiome in a high-fat diet- and streptozotocin-induced mouse model of type 2 diabetes mellitus
Dan Shen
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Data curation, Investigation, Writing - original draft
Search for more papers by this authorYingjian Lu
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Formal analysis, Resources, Supervision, Writing - review & editing
Search for more papers by this authorShuhua Tian
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Formal analysis, Investigation, Project administration, Software, Visualization
Search for more papers by this authorShaotong Ma
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Formal analysis, Investigation
Search for more papers by this authorJing Sun
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Formal analysis, Visualization
Search for more papers by this authorQiaobin Hu
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Conceptualization, Data curation, Formal analysis
Search for more papers by this authorXinyi Pang
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Investigation, Visualization
Search for more papers by this authorCorresponding Author
Xiangfei Li
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Correspondence
Xiangfei Li, College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, P. R. China.
Email: [email protected]
Contribution: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Resources
Search for more papers by this authorDan Shen
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Data curation, Investigation, Writing - original draft
Search for more papers by this authorYingjian Lu
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Formal analysis, Resources, Supervision, Writing - review & editing
Search for more papers by this authorShuhua Tian
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Formal analysis, Investigation, Project administration, Software, Visualization
Search for more papers by this authorShaotong Ma
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Formal analysis, Investigation
Search for more papers by this authorJing Sun
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Formal analysis, Visualization
Search for more papers by this authorQiaobin Hu
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Conceptualization, Data curation, Formal analysis
Search for more papers by this authorXinyi Pang
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Contribution: Investigation, Visualization
Search for more papers by this authorCorresponding Author
Xiangfei Li
College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, P. R. China
Correspondence
Xiangfei Li, College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, P. R. China.
Email: [email protected]
Contribution: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Resources
Search for more papers by this authorAbstract
L-arabinose is a good and healthy food additive. This study was conducted to investigate the effect of L-arabinose in a mouse model of type 2 diabetes mellitus (T2DM) induced by exposure to a high-fat diet (HFD) and streptozotocin (STZ). The model mice received L-arabinose at 20 and 60 mg (kg body weight [bw])−1d−1, metformin at 300 mg (kg bw)−1d−1 (positive control) or sterile water (control) via oral gavage. Compared with the model group, mice treated with L-arabinose exhibited attenuated symptoms of diabetes mellitus, including a slower rate of body weight loss, increased homeostasis model assessment of β-cell function index levels, decreased blood glucose, alleviation of steatosis, and repair of pancreatic islet cells. L-arabinose also exerted an anti-inflammatory effect and partially mitigated dyslipidemia. A 16S-rRNA sequence analysis of the gut microbiota revealed that at the phylum level, treatment with L-arabinose significantly reduced the ratio of Firmicutes to Bacteroidetes due to a decreased relative abundance of Firmicutes; at the genus level, it reversed the increase in the relative abundance of Allobaculum and the decrease abundance of Oscillospira caused by exposure to an HFD and STZ. And the model mice received L-arabinose at 20 mg (kg bw)−1d−1 had a better effect on improving T2DM than the high-dose group supplemented L-arabinose at 60 mg (kg bw)−1d−1. These results strongly suggest L-arabinose as an excellent candidate supplement to prevent or treat T2DM.
Practical applications
L-arabinose, xylitol and sucralose are well-known substitutes for sucrose. L-arabinose has been reported to have beneficial effects on hyperglycemia, glycemic index, and fat accumulation. In this study, we found that low-dose (20 mg (kg bw)−1d-1) supplementation of L-arabinose significantly improved glucose intolerance and gut microbiota incoordination in T2DM caused by HFD and STZ.
CONFLICT OF INTEREST
The authors have declared no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- Abdel-Mobdy, A. E., Khattab, M. S., Mahmoud, E. A., Mohamed, E. R., & Abdel-Rahim, E. A. (2021). Semi-modified okara whey diet increased insulin secretion in diabetic rats fed a basal or high fat diet. Food Science and Biotechnology, 30(1), 107–116. https://doi.org/10.1007/s10068-020-00842-3
- American Diabetes, A. (2011). Executive summary: Standards of medical care in diabetes–2011. Diabetes Care, 34(Suppl 1), S4–S10. https://doi.org/10.2337/dc11-S004
- American Diabetes, A. (2014). Diagnosis and classification of diabetes mellitus. Diabetes Care, 37(Suppl 1), S81–S90. https://doi.org/10.2337/dc14-S081
- Betteridge, D. J. (2000). What is oxidative stress? Metabolism, 49(2 Suppl 1), 3–8. https://doi.org/10.1016/s0026-0495(00)80077-3
- Bonadonna, R. C., Blonde, L., Antsiferov, M., Berria, R., Gourdy, P., Hatunic, M., Mohan, V., & Horowitz, M. (2017). Lixisenatide as add-on treatment among patients with different beta-cell function levels as assessed by HOMA-beta index. Diabetes/Metabolism Research and Reviews, 33(6), e2897. https://doi.org/10.1002/dmrr.2897
- Bozcaarmutlu, A., Sapmaz, C., Bozdoğan, Ö., Kükner, A., Kılınç, L., Kaya, S. T., Özarslan, O. T., & Ekşioğlu, D. (2020). The effect of co-administration of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rat liver. Drug and Chemical Toxicology, 1–9. https://doi.org/10.1080/01480545.2020.1802475
- Buse, J. B. (2011). Type 2 diabetes mellitus in 2010: Individualizing treatment targets in diabetes care. Nature Reviews Endocrinology, 7(2), 67–68. https://doi.org/10.1038/nrendo.2010.230
- Chatterjee, S., Khunti, K., & Davies, M. J. (2017). Type 2 diabetes. The Lancet, 389(10085), 2239–2251. https://doi.org/10.1016/s0140-6736(17)30058-2
- Chen, D., Chen, G., Ding, Y. U., Wan, P., Peng, Y., Chen, C., Ye, H., Zeng, X., & Ran, L. (2019). Polysaccharides from the flowers of tea (Camellia sinensis L.) modulate gut health and ameliorate cyclophosphamide-induced immunosuppression. Journal of Functional Foods, 61, 103470. https://doi.org/10.1016/j.jff.2019.103470
- Chen, P., Zhang, Q., Dang, H., Liu, X., Tian, F., Zhao, J., Chen, Y., Zhang, H., & Chen, W. (2014). Oral administration of Lactobacillus rhamnosus CCFM0528 improves glucose tolerance and cytokine secretion in high-fat-fed, streptozotocin-induced type 2 diabetic mice. Journal of Functional Foods, 10, 318–326. https://doi.org/10.1016/j.jff.2014.06.014
- Dhuique-Mayer, C., Gence, L., Portet, K., Tousch, D., & Poucheret, P. (2020). Preventive action of retinoids in metabolic syndrome/type 2 diabetic rats fed with citrus functional food enriched in beta-cryptoxanthin. Food & Function, 11(10), 9263–9271. https://doi.org/10.1039/d0fo02430a
- Ding, Y., Xu, M., Lu, Q., Wei, P., Tan, J., & Liu, R. (2019). Combination of honey with metformin enhances glucose metabolism and ameliorates hepatic and nephritic dysfunction in STZ-induced diabetic mice. Food & Function, 10(11), 7576–7587. https://doi.org/10.1039/c9fo01575b
- DiSogra, R. M., & Meece, J. (2019). Auditory and vestibular side effects of FDA-approved drugs for diabetes. Seminars in Hearing, 40(4), 315–326. https://doi.org/10.1055/s-0039-1697645
- Forsman, J. J., & Leino, R. (2011). L-Pentoses in biological and medicinal applications. Chemical Reviews, 111(5), 3334–3357. https://doi.org/10.1021/cr1002563
- Franks, P. W., & McCarthy, M. I. (2016). Exposing the exposures responsible for type 2 diabetes and obesity. Science, 354(6308), 69–73. https://doi.org/10.1126/science.aaf5094
- Giaccari, A., Solini, A., Frontoni, S., & Del Prato, S. (2021). Metformin benefits: Another example for alternative energy substrate mechanism? Diabetes Care, 44(3), 647–654. https://doi.org/10.2337/dc20-1964
- Gu, C., Yang, Y. E., Xiang, H., Li, S., Liang, L., Sui, H., Zhan, L., & Lu, X. (2016). Deciphering bacterial community changes in Zucker diabetic fatty rats based on 16S rRNA gene sequences analysis. Oncotarget, 7(31), 48941–48952. https://doi.org/10.18632/oncotarget.10597
- Hao, L., Lu, X., Sun, M., Li, K., Shen, L., & Wu, T. (2015). Protective effects of L-arabinose in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats. Food & Nutrition Research, 59, 28886. https://doi.org/10.3402/fnr.v59.28886
- Herman, W. (2017). The global burden of diabetes: An overview. Diabetes Mellitus in Developing Countries and Underserved Communities,1–5. DOI:10.1007/978-3-31-41559-8_1
- Hu, B., Li, H., Wang, Q., Tan, Y., Chen, R., Li, J., Ban, W., & Liang, L. (2018). Production and utilization of L-Arabinose in China. World Journal of Engineering and Technology, 6(03), 24–36. https://doi.org/10.4236/wjet.2018.63B004
10.4236/wjet.2018.63B004 Google Scholar
- Jin, D., Zhang, B., Li, Q., Tu, J., & Zhou, B. (2020). Effect of punicalagin on multiple targets in streptozotocin/high-fat diet-induced diabetic mice. Food & Function, 11(12), 10617–10634. https://doi.org/10.1039/d0fo01275k
- Kanikarla-Marie, P., & Jain, S. K. (2015). Role of hyperketonemia in inducing oxidative stress and cellular damage in cultured hepatocytes and type 1 diabetic rat liver. Cellular Physiology and Biochemistry, 37(6), 2160–2170. https://doi.org/10.1159/000438573
- Kanoski, S. E., & Davidson, T. L. (2011). Western diet consumption and cognitive impairment: Links to hippocampal dysfunction and obesity. Physiology & Behavior, 103(1), 59–68. https://doi.org/10.1016/j.physbeh.2010.12.003
- Khat-Udomkiri, N., Toejing, P., Sirilun, S., Chaiyasut, C., & Lailerd, N. (2020). Antihyperglycemic effect of rice husk derived xylooligosaccharides in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rat model. Food Sciences and Nutrition, 8(1), 428–444. https://doi.org/10.1002/fsn3.1327
- Krog-Mikkelsen, I., Hels, O., Tetens, I., Holst, J. J., Andersen, J. R., & Bukhave, K. (2011). The effects of L-arabinose on intestinal sucrase activity: Dose-response studies in vitro and in humans. American Journal of Clinical Nutrition, 94(2), 472–478. https://doi.org/10.3945/ajcn.111.014225
- Li, X., Chen, L., Zhu, X., Lu, Z., & Lu, Y. (2020). Effect of gamma-aminobutyric acid-rich yogurt on insulin sensitivity in a mouse model of type 2 diabetes mellitus. Journal of Dairy Science, 103(9), 7719–7729. https://doi.org/10.3168/jds.2019-17757
- Liu, T. Y., Shi, C. X., Gao, R., Sun, H. J., Xiong, X. Q., Ding, L., Chen, Q., Li, Y. H., Wang, J. J., Kang, Y. M., & Zhu, G. Q. (2015). Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes. Clinical Science (London), 129(10), 839–850. https://doi.org/10.1042/CS20150009
- Liu, X., Zhu, D., Sun, L., Gao, Y., & Wang, C. (2013). Effect of L-arabinose on the postprandial blood glucose and body weight. Wei Sheng Yan Jiu, 42(2), 295–297. https://www.ncbi.nlm.nih.gov/pubmed/23654110
- Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985). Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 28(7), 412–419. https://doi.org/10.1007/BF00280883
- Muskiet, M. H. A., Tonneijck, L., Smits, M. M., Kramer, M. H. H., Ouwens, D. M., Hartmann, B., Holst, J. J., Touw, D. J., Danser, A. J., Joles, J. A., & van Raalte, D. H. (2020). Effects of DPP-4 Inhibitor Linagliptin versus Sulfonylurea Glimepiride as add-on to metformin on renal physiology in overweight patients with type 2 diabetes (RENALIS): A randomized, double-blind trial. Diabetes Care, 43(11), 2889–2893. https://doi.org/10.2337/dc20-0902
- Obaroakpo, J. U., Nan, W., Hao, L., Liu, L., Zhang, S., Lu, J., Pang, X., & Lv, J. (2020). The hyperglycemic regulatory effect of sprouted quinoa yoghurt in high-fat-diet and streptozotocin-induced type 2 diabetic mice via glucose and lipid homeostasis. Food & Function, 11(9), 8354–8368. https://doi.org/10.1039/d0fo01575j
- Osaki, S., Kimura, T., Sugimoto, T., Hizukuri, S., & Iritani, N. (2001). L-Arabinose feeding prevents increases due to dietary sucrose in lipogenic enzymes and triacylglycerol levels in rats. The Journal of Nutrition, 131(3), 796–799. https://doi.org/10.1093/jn/131.3.796
- Pan, Y., Wang, C., Chen, Z., Li, W., Yuan, G., & Chen, H. (2017). Physicochemical properties and antidiabetic effects of a polysaccharide from corn silk in high-fat diet and streptozotocin-induced diabetic mice. Carbohydrate Polymers, 164, 370–378. https://doi.org/10.1016/j.carbpol.2017.01.092
- Rahier, J., Guiot, Y., Goebbels, R. M., Sempoux, C., & Henquin, J. C. (2008). Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes, Obesity & Metabolism, 10(Suppl 4), 32–42. https://doi.org/10.1111/j.1463-1326.2008.00969.x
- Rehfeld, J. F., Knop, F. K., & Asmar, M. (2019). Gastrin secretion in normal subjects and diabetes patients is inhibited by glucagon-like peptide 1: A role in the gastric side effects of GLP-1-derived drugs? Scandinavian Journal of Gastroenterology, 54(12), 1448–1451. https://doi.org/10.1080/00365521.2019.1690673
- Rosenson, R. S. (2005). HDL-C and the diabetic patient: Target for therapeutic intervention? Diabetes Research and Clinical Practice, 68(Suppl 2), S36–42. https://doi.org/10.1016/j.diabres.2005.03.013
- Seri, K., Sanai, K., Matsuo, N., Kawakubo, K., Xue, C., & Inoue, S. (1996). L-arabinose selectively inhibits intestinal sucrase in an uncompetitive manner and suppresses glycemic response after sucrose ingestion in animals. Metabolism, 45(11), 1368–1374. https://doi.org/10.1016/s0026-0495(96)90117-1
- Shaw, J. E., Sicree, R. A., & Zimmet, P. Z. (2010). Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice, 87(1), 4–14. https://doi.org/10.1016/j.diabres.2009.10.007
- Shibanuma, K., Degawa, Y., & Houda, K. (2011). Determination of the transient period of the EIS complex and investigation of the suppression of blood glucose levels by L-arabinose in healthy adults. European Journal of Nutrition, 50(6), 447–453. https://doi.org/10.1007/s00394-010-0154-3
- Song, Y. B., Kim, B., Choi, M. J., Song, Y. O., & Cho, E. J. (2012). Protective effect of arabinose and sugar beet pulp against high glucose-induced oxidative stress in LLC-PK1 cells. Food Chemistry, 134(1), 189–194. https://doi.org/10.1016/j.foodchem.2012.02.091
- Ueno, H., Tsuchimochi, W., Wang, H.-W., Yamashita, E., Tsubouchi, C., Nagamine, K., Sakoda, H., & Nakazato, M. (2015). Effects of miglitol, acarbose, and sitagliptin on plasma insulin and gut peptides in type 2 diabetes mellitus: A crossover study. Diabetes Therapy, 6(2), 187–196. https://doi.org/10.1007/s13300-015-0113-3
- Wang, G., Li, X., Zhao, J., Zhang, H., & Chen, W. (2017). Lactobacillus casei CCFM419 attenuates type 2 diabetes via a gut microbiota dependent mechanism. Food & Function, 8(9), 3155–3164. https://doi.org/10.1039/c7fo00593h
- Wang, X., Yao, X., Ying, Y., Liu, J., Wang, Z., Xiang, X., Yi, Y., & Yang, Y. (2012). Effect of L-arabinose on glucose and lipid metabolism in type 2 diabetic rats. Wei Sheng Yan Jiu, 41(2), 260–263, 267. https://www.ncbi.nlm.nih.gov/pubmed/22611937
- Wang, Y., Guan, Y., Xue, L., Liu, J., Yang, Z., Nie, C., Yan, Y., Liu, S., Sun, J., Fan, M., Qian, H., Ying, H., Li, Y., & Wang, L. (2021). L-Arabinose suppresses gluconeogenesis through modulating AMP-activated protein kinase in metabolic disorder mice. Food & Function, 12(4), 1745–1756. https://doi.org/10.1039/d0fo02163f
- Winkler, G., Kiss, S., Keszthelyi, L., Sapi, Z., Ory, I., Salamon, F., Kovacs, M., Vargha, P., Szekeres, O., Speer, G., Karadi, I., Sikter, M., Kaszas, E., Dworak, O., Gero, G., & Cseh, K. (2003). Expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-alpha, soluble serum TNF-receptor-2 concentrations and C-peptide level. European Journal of Endocrinology, 149(2), 129–135. https://doi.org/10.1530/eje.0.1490129
- Wu, C.-Y., Zhou, J., Long, F., Zhang, W., Shen, H., Zhu, H. E., Xu, J.-D., & Li, S.-L. (2020). Similar hypoglycemic effects of glucomannan and its enzyme degraded products from Amorphophallus albus on type 2 diabetes mellitus in mice and potential mechanisms. Food & Function, 11(11), 9740–9751. https://doi.org/10.1039/d0fo02434a
- Yazdan, P. R., Esmaeili, A. M., & Ashrafi, H. J. (2005). Teucrium polium extract effects pancreatic function of streptozotocin diabetic rats: A histopathological examination. Iranian Biomedical Journal, 9(2), 81–85.
- Zhang, M., Du, N., Wang, L. U., Wang, X., Xiao, Y., Zhang, K., Liu, Q., & Wang, P. (2017). Conjugated fatty acid-rich oil from Gynostrmma pentaphyllum seed can ameliorate lipid and glucose metabolism in type 2 diabetes mellitus mice. Food & Function, 8(10), 3696–3706. https://doi.org/10.1039/c7fo00712d
- Zhao, L., Wang, Y., Zhang, G., Zhang, T., Lou, J., & Liu, J. (2019). L-Arabinose elicits gut-derived hydrogen production and ameliorates metabolic syndrome in C57BL/6J mice on high-fat-diet. Nutrients, 11(12), 3054. https://doi.org/10.3390/nu11123054
- Zou, Y., Ju, X., Chen, W., Yuan, J., Wang, Z., Aluko, R. E., & He, R. (2020). Rice bran attenuated obesity via alleviating dyslipidemia, browning of white adipocytes and modulating gut microbiota in high-fat diet-induced obese mice. Food & Function, 11(3), 2406–2417. https://doi.org/10.1039/c9fo01524h