Role of α-Amylase and α-Glucosidase (Key Enzymes Linked to Type 2 Diabetes) Activities in the Management/Prevention of Diabetes Mellitus

References

[1] American Diabetes Association.. Standards of medical care in diabetes—2023. Diabetes Care, 46, S1–S284.

[2] Ye, J., Wu, Y., Yang, S., Zhu, D., Chen, F., Chen, J., Ji, X. and Hou, K. (2023). The global, regional and national burden of type 2 diabetes mellitus in the past, present and future: a systematic analysis of the Global Burden of Disease Study 2019. Frontiers in endocrinology, 14, 1192629.

[3] Seuring, T., Archangelidi, O. and Suhrcke, M. (2015). The Economic Costs of Type 2 Diabetes: A Global Systematic Review. PharmacoEconomics, 33(8), 811–831. 

[4] Ceriello, A. (2018). Postprandial hyperglycemia and cardiovascular complications of diabetes: An update. Nutrition, Metabolism and Cardiovascular Diseases, 28, 157–159.

[5] Lam, T. P., Tran, N. N., Pham, L. D., Lai, N. V., Dang, B. N., Truong, N. N., Nguyen-Vo, S. K., Hoang, T. L., Mai, T. T. and Tran, T. D. (2024). Flavonoids as dual-target inhibitors against α-glucosidase and α-amylase: a systematic review of in vitro studies. Natural products and bioprospecting, 14(1), 4.

[6] Falchi, M., El-Sayed Moustafa, J. S., and Takousis, P. (2014). Low copy number of the salivary amylase gene predisposes to obesity. Nature Genetics, 46, 492–497.

[7] Viljakainen, H., Andersson-Assarsson, J. C. and Armenio, M. (2015). Low copy number of the AMY1 locus is associated with early-onset female obesity in Finland. PLOS ONE, 10, e0132882.

[8] Bischoff, H. (1994) Pharmacology of α-glucosidase inhibition. European Journal of Clinical Investigation, 24, 3–10.

[9] Lebovitz, H. E. (1997). Alpha-glucosidase inhibitors. Endocrinology and Metabolism Clinics of North America, 26, 539–551.

[10] Tahrani, A. A., Barnett, A. H. and Bailey, C. J. (2016). Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus. Nature Reviews Endocrinology, 12, 566–592.

[11] Proença, C., Ribeiro, D. and Freitas, M. (2021). Flavonoids as potential agents in the management of type 2 diabetes through the modulation of α-amylase and α-glucosidase activity: A review. Critical Reviews in Food Science and Nutrition, 62, 4157–4178.

[12] van der Maarel, M. J. E. C., van der Veen, B., Uitdehaag, J. C. M., Leemhuis, H. and Dijkhuizen, L. (2002). Properties and applications of starch-converting enzymes of the α-amylase family. Journal of Biotechnology, 94(2), 137–155.

[13] Lo Piparo, E., Scheib, H., Frei, N., Williamson, G., Grigorov, M. and Chou, C. J. (2008). Flavonoids for controlling starch digestion: Structural requirements for inhibiting human α-amylase. Journal of Medicinal Chemistry, 51(12), 3555–3561.

[14] Visvanathan, R., Houghton, M. J. and Barber, E. (2024). Structure-function relationships in (poly)phenol-enzyme binding: Direct inhibition of human salivary and pancreatic α-amylases. Food Chemistry, 444, 138621.

[15] Erta, G., Gersone, G., Jurka, A. and Tretjakovs, P. (2025). Decoding metabolic connections: The role of salivary amylase activity in modulating visceral fat and triglyceride glucose index. Lipids in Health and Disease, 24, Article 98.

[16] Peyrot des Gachons, C. and Breslin, P. A. S. (2016). Salivary amylase: Digestion and metabolic syndrome. Current Diabetes Reports, 16(10), Article 102.

[17] Sales, P. M., Souza, P. M., Simeoni, L. A. and Silveira, D. (2012). α-Amylase inhibitors: A review of raw material and isolated compounds from plant source. Journal of Pharmacy & Pharmaceutical Sciences, 15(1), 141–183.

[18] Ali, H., Houghton, P. J. and Soumyanath, A (2006). α-Amylase inhibitory activity of some Malaysian plants used to treat diabetes; with particular reference to Phyllanthus amarus. Journal of Ethnopharmacology, 107, 449–455.

[19] Adefegha, S. A. and Oboh, G. (2013). Phytochemistry and mode of action of some tropical spices in the management of type-2 diabetes and hypertension. African Journal of Pharmacy and Pharmacology, 7(7), 332–346.

[20] Kim, Y., Keogh, J. B. and Clifton, P. M. (2016). Polyphenols and glycemic control. Nutrients, 8(1), 17.

[21] Monnier, L., Mas, E., Ginet, C., Michel, F., Villon, L., Cristol, J. P. and Colette, C. (2006). Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. Journal of the American Medical Association (JAMA), 295(14), 1681–1687.

[22] Ko, S.-H., Kim, S.-R., Kim, D.-J., Oh, S.-J., Lee, H.-J., Shim, K.-H., Woo, M.-H., Kim, J.-Y., Kim, N.-H., Kim, J.-T., Kim, C. H., Kim, H. J., Jeong, I.-K., Hong, E.-G., Cho, J.-H., Mok, J.-O. and Yoon, K.-H. (2011). 2011 clinical practice guidelines for type 2 diabetes in Korea. Diabetes & Metabolism Journal, 35(5), 431–436.

[23] Nathan, N., Janssen, L., Sutherland, R., Hodder, R. K., Evans, C. E. L., Booth, D., Yoong, S. L., Reilly, K., Finch, M. and Wolfenden, L. (2019). The effectiveness of lunchbox interventions on improving the foods and beverages packed and consumed by children at centre-based care or school: A systematic review and meta-analysis. International Journal of Behavioral Nutrition and Physical Activity, 16, Article 38.

[24] Fowler, M. J. (2008. Microvascular and macrovascular complications of diabetes. Clinical Diabetes, 26, 77–82.

[25] Zhu, J., Chen, C., Zhang, B. and Huang, Q. (2020). The inhibitory effects of flavonoids on α-amylase and α-glucosidase. Critical Reviews in Food Science and Nutrition, 60(4), 695–708.

[26] Xu, W., Shao, R. and Xiao, J. (2015). Is there consistency between the binding affinity and inhibitory potential of natural polyphenols as α-amylase inhibitors? Journal of Agricultural and Food Chemistry, 63, 8571–8577.

[27] Chiasson, J. L., Josse, R. G., Gomis, R., Hanefeld, M., Karasik, A., Laakso, M. and STOP-NIDDM Trial Research Group. (2002). Acarbose for prevention of type 2 diabetes mellitus: The STOP-NIDDM randomised trial. The Lancet, 359(9323), 2072–2077.

[28] Khader, Y., Abu Khudair, S., Tanaka, E., Kufoof, L., Al Nsour, M., Aqel, A., Al-Dubai, S. A. R., Alblihed, M., Altammemi, A. B., Obeidat, S., Alzoubi, K. H., Al-Horani, H., Khader, A., AlAli, A., AlMannai, M., Abdel-Razeq, H. and Ghandour, R. (2024). Psychosocial, emotional and behavioral problems, quality of life, and mental health care-seeking behaviors among children and adolescents in Jordan: A national school-based survey. Frontiers in Public Health, 12, Article 1409158.

[29] Holman, R. R., Coleman, R. L., Chan, J. C. N., Chiasson, J. L., Feng, H., Ge, J., Gerstein, H. C., Gray, R., Huo, Y., McMurray, J. J. V., Rydén, L., Schröder, S., Sun, Y., Theodorakis, M. J., Tendera, M., Tucker, L., Tuomilehto, J., Wei, Y., Yang, W., Wang, D., Hu, D., Pan, C. and ACE Study Group. (2017). Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): A randomised, double-blind, placebo-controlled trial. The Lancet Diabetes & Endocrinology, 5(11), 877–886.

[30] Holman, R. R. (2018). What does the Acarbose Cardiovascular Evaluation (ACE) trial tell us? Journal of Diabetes, 10(8), 683–685.

[31] Standl, E., Theodorakis, M. J., Erbach, M., Schnell, O. and Tuomilehto, J. (2014). On the potential of acarbose to reduce cardiovascular disease. Cardiovascular diabetology, 13, 81.

[32] Derosa, G., and Maffioli, P. (2012). Anti-obesity drugs: a review about their effects and their safety. Expert opinion on drug safety, 11(3), 459–471.

[33] van de Laar, F. A., Lucassen, P. L. B. J., Akkermans, R. P., van de Lisdonk, E. H., Rutten, G. E. H. M. and van Weel, C. (2005). Alpha-glucosidase inhibitors for patients with type 2 diabetes: Results from a Cochrane systematic review and meta-analysis. Diabetes Care, 28(1), 154–163.

[34] Patel, D. K., and Patel, K. (2015). Medicinal plants with potential anti-diabetic properties: A review. American Journal of Phytomedicine and Clinical Therapeutics, 3(2), 98–107.

[35] Tundis, R., Loizzo, M. R. and Menichini, F. (2010). Natural products as α-amylase and α-glucosidase inhibitors and their hypoglycaemic potential in the treatment of diabetes: An update. Mini-Reviews in Medicinal Chemistry, 10, 315–331.

[36] Kim, Y. M., Jeong, Y. K., Wang, M. H., Lee, W. Y. and Rhee, H. I. (2005). Inhibitory effect of pine extract on alpha-glucosidase activity and postprandial hyperglycemia. Nutrition (Burbank, Los Angeles County, Calif.), 21(6), 756–761.

[37] Adisakwattana, S., Sompong, W., Meeprom, A., Ngamukote, S. and Yibchok-Anun, S. (2012). Cinnamic acid and its derivatives inhibit fructose-mediated protein glycation. International Journal of Molecular Sciences, 13(2), 1778–1789.

[38] Hedrington, M. S. and Davis, S. N. (2019). Considerations when using alpha-glucosidase inhibitors in the treatment of type 2 diabetes. Expert opinion on pharmacotherapy, 20(18), 2229–2235.

[39] Nie, A., Su, X., Zhang, S., Guan, W. and Li, J. (2020). Psychological impact of COVID-19 outbreak on frontline nurses: A cross-sectional survey study. Journal of clinical nursing, 29(21-22), 4217–4226.

[40] Singh, J., Kaur, H., Singh, B., Sharma, S., Kaur, G., Kaur, A., Singh, B. and Arora, S. (2019). Phytochemical analysis and in vitro assessment of antioxidant, anti-diabetic and anti-inflammatory activities of Morus alba L. leaves. Scientific Reports, 9, Article 15259.

[41] Zhong, S., Qi, L., Huo, J., Wang, Y., Liu, Y., Zhang, H., Li, X. and Chen, Y. (2023). Mesoporous polydopamine and inulin hydrogel for improved deoxynojirimycin effect in type 2 diabetes mellitus management. International Journal of Biological Macromolecules, 244, 125037.

[42] Hunt, N. J., Lockwood, G. P., Heffernan, S. J., Daymond, J., Ngu, M., Narayanan, R. K., Westwood, L. J., Mohanty, B., Esser, L., Williams, C. C., Kuncic, Z., McCourt, P. A. G., Le Couteur, D. G. and Cogger, V. C. (2024). Oral nanotherapeutic formulation of insulin with reduced episodes of hypoglycaemia. Nature nanotechnology, 19(4), 534–544.

[43] DeFronzo, R. A., Abdul-Ghani, M., Norton, L. and Nissen, S. E. (2014). Combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists. Diabetes Care, 37(12), 3309–3316.

[44] De Block, C. E., De Leeuw, I. H., Bogers, J. J., Pelckmans, P. A., Ieven, M. M., Van Marck, E. A., Van Acker, K. L. and Van Gaal, L. F. (2003). Autoimmune gastropathy in type 1 diabetic patients with parietal cell antibodies: histological and clinical findings. Diabetes care, 26(1), 82–88. 

[45] Goldstein, B. J., Gomis, R., Lee, H.-K. and Leiter, L. A., on behalf of the Global Partnership for Effective Diabetes Management. (2007). Type 2 diabetes—Treat early, treat intensively. International Journal of Clinical Practice, 61(Suppl. 157), 16–21.

[46] Mantsiou, C., Karagiannis, T., Kakotrichi, P., Malandris, K., Avgerinos, I., Liakos, A., Tsapas, A. and Bekiari, E. (2020). Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors as combination therapy for type 2 diabetes: A systematic review and meta-analysis. Diabetes, obesity & metabolism, 22(10), 1857–1868.

[47] Davies, M. J., Aroda, V. R., Collins, B. S., Gabbay, R. A., Green, J., Maruthur, N. M., Rosas, S. E., Del Prato, S., Mathieu, C., Mingrone, G., Rossing, P., Tankova, T., Tsapas, A. and Buse, J. B. (2022). Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care, 45(11), 2753–2786.

[48] Gkouskou, K. K., Grammatikopoulou, M. G., Lazou, E., Vasilogiannakopoulou, T., Sanoudou, D. and Eliopoulos, A. G. (2024). A genomics perspective of personalized prevention and management of obesity. Human genomics, 18(1), 4.

[49] Agius L. (2015). Role of glycogen phosphorylase in liver glycogen metabolism. Molecular aspects of medicine, 46, 34–45. 

[50] Lin, X., Xu, Y., Pan, X., Xu, J., Ding, Y., Sun, X., Song, X., Ren, Y. and Shan, P. F. (2020). Global, regional, and national burden and trend of diabetes in 195 countries and territories: an analysis from 1990 to 2025. Scientific reports, 10(1), 14790.

@article{1719443,
      author = {Bada, S. O.},
      title = {Role of α-Amylase and α-Glucosidase (Key Enzymes Linked to Type 2 Diabetes) Activities in the Management/Prevention of Diabetes Mellitus},
      journal = {Iconic Research And Engineering Journals},
      year = {2021},
      volume = {5},
      number = {4},
      pages = {447-457},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1719443.pdf},
      abstract = {Type 2 diabetes mellitus (T2DM) is a chronic, progressive metabolic disorder characterized by insulin resistance, progressive β-cell dysfunction, and persistent hyperglycemia, with postprandial hyperglycemia frequently prededing fasting glucose abnormalities in early disease. The global burden of diabetes continues to rise at an alarming rate. The International Diabetes Federation estimated that 10.5% of adults aged 20–79 years were living with diabetes in 2021, with prevalence projected to increase to 11.3% by 2030 and 12.2% by 2045. Approximately 90% of these cases are attributable to type 2 diabetes mellitus (T2DM), highlighting its dominant contribution to the worldwide diabetes epidemic. α-Amylase (EC 3.2.1.1) and α-glucosidase (EC 3.2.1.20) are brush-border and pancreatic enzymes that sequentially hydrolyze complex dietary carbohydrates into glucose. Because their catalytic efficiency directly governs the rate of postprandial glucose inflow into the circulation, pharmacological inhibition of these enzymes has emerged as a rational and clinically validated strategy to attenuate PPHG and its associated metabolic and cardiovascular sequelae. The present review critically examines the structure, physiological function, and pathophysiological contributions of α-amylase and α-glucosidase; collates mechanistic, preclinical, and clinical evidence supporting synthetic (acarbose, miglitol, voglibose) and naturally derived inhibitors; discusses recent advances in nanocarrier-based delivery and structure-guided inhibitor design; and evaluates the emerging roles of combination therapy, nutrigenomics, and personalized medicine. It is therefore concluded that, despite the challenges posed by gastrointestinal adverse effects and inter-individual variability, enzyme inhibition remains a cornerstone of multimodal therapeutic strategies for type 2 diabetes mellitus (T2DM), with significant potential for further optimization through the development of more selective, effective, and better-tolerated agents.},
      keywords = {α-Amylase, α-Glucosidase, Type 2 Diabetes Mellitus, Postprandial Hyperglycemia, Enzyme Inhibition, Acarbose, Flavonoids, Nanocarriers, Nutrigenomics},
      month = {October},
      doi = {https://doi.org/10.64388/IREV5I4-1719443}
  }