Abstract
Background and Objective: Diabetes mellitus is the third leading cause of death in Indonesia (6.7 %), followed by stroke (21.1 %) and coronary heart disease (12.9 %). The prevalence of diabetes worldwide continues to increase on a yearly basis, including in Indonesia. Diabetes is a significant burden for many countries due to the high costs of treatment and reduced productivity of diabetes patients. Comprehensive strategies to prevent and treat diabetes are therefore mandatory. Oral hypoglycemic drugs are the first-line therapy for diabetes mellitus patients; however, these oral drugs still have several side effects. Therefore, it is necessary to conduct studies on medicinal plants with hypoglycemic effects to identify substances that have an anti-diabetic potential resembling physiological processes in the body. Indonesian people often use herbal medicines empirically, but the benefits have not been scientifically documented. Melinjo (Gnetum gnemon L.) is a native Indonesian gymnosperm plant, and the seeds are often processed into food. Melinjo seeds extract contains many polyphenols, including trans-resveratrol.
Conclusion: Studies on the health benefits of resveratrol are widely available, including antidiabetes and blood sugar control in patients with type 2 diabetes.
Keywords: Anti-diabetic, Gnetum gnemon L., melinjo seed extract, resveratrol, type 2 diabetes mellitus, metabolism.
[1]
Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 2014; 383(9922): 1068-83.
[http://dx.doi.org/10.1016/S0140-6736(13)62154-6] [PMID: 24315620]
[http://dx.doi.org/10.1016/S0140-6736(13)62154-6] [PMID: 24315620]
[2]
Schwartz SS, Epstein S, Corkey BE, Grant SF, Gavin JR III, Aguilar RB. The time is right for a new classification system for diabetes: Rationale and implications of the β-cell-centric classification schema. Diabetes Care 2016; 39(2): 179-86.
[http://dx.doi.org/10.2337/dc15-1585] [PMID: 26798148]
[http://dx.doi.org/10.2337/dc15-1585] [PMID: 26798148]
[3]
Dimitriadis G, Mitrou P, Lambadiari V, Maratou E, Raptis SA. Insulin effects in muscle and adipose tissue. Diabetes Res Clin Pract 2011; 93 (Suppl. 1): S52-9.
[http://dx.doi.org/10.1016/S0168-8227(11)70014-6] [PMID: 21864752]
[http://dx.doi.org/10.1016/S0168-8227(11)70014-6] [PMID: 21864752]
[4]
Zhou B, Lu Y, Hajifathalian K, et al. Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 2016; 387(10027): 1513-30.
[http://dx.doi.org/10.1016/S0140-6736(16)00618-8] [PMID: 27061677]
[http://dx.doi.org/10.1016/S0140-6736(16)00618-8] [PMID: 27061677]
[5]
Galicia-Garcia U, Benito-Vicente A, Jebari S, et al. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci 2020; 21(17): 6275.
[http://dx.doi.org/10.3390/ijms21176275] [PMID: 32872570]
[http://dx.doi.org/10.3390/ijms21176275] [PMID: 32872570]
[6]
Wong ND, Zhao Y, Patel R, et al. Cardiovascular risk factor targets and cardiovascular disease event risk in diabetes: A pooling project of the atherosclerosis risk in communities study, multi-ethnic study of atherosclerosis, and jackson heart study. Diabetes Care 2016; 39(5): 668-76.
[http://dx.doi.org/10.2337/dc15-2439] [PMID: 27208374]
[http://dx.doi.org/10.2337/dc15-2439] [PMID: 27208374]
[7]
Buse JB, Wexler DJ, Tsapas A, et al. 2019 update to: Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020; 43(2): 487-93.
[http://dx.doi.org/10.2337/dci19-0066] [PMID: 31857443]
[http://dx.doi.org/10.2337/dci19-0066] [PMID: 31857443]
[8]
McGovern A, Tippu Z, Hinton W, Munro N, Whyte M, de Lusignan S. Comparison of medication adherence and persistence in type 2 diabetes: A systematic review and meta-analysis. Diabetes Obes Metab 2018; 20(4): 1040-3.
[http://dx.doi.org/10.1111/dom.13160] [PMID: 29135080]
[http://dx.doi.org/10.1111/dom.13160] [PMID: 29135080]
[9]
Fullerton MD, Steinberg GR. SIRT1 takes a backseat to AMPK in the regulation of insulin sensitivity by resveratrol. Diabetes 2010; 59(3): 551-3.
[http://dx.doi.org/10.2337/db09-1732] [PMID: 20190133]
[http://dx.doi.org/10.2337/db09-1732] [PMID: 20190133]
[10]
Christensen AA, Gannon M. The beta cell in type 2 diabetes. Curr Diab Rep 2019; 19(9): 81.
[http://dx.doi.org/10.1007/s11892-019-1196-4] [PMID: 31399863]
[http://dx.doi.org/10.1007/s11892-019-1196-4] [PMID: 31399863]
[11]
Power D. Standards of medical care in diabetes. Diabetes Care 2006; 29(2): 476.
[http://dx.doi.org/10.2337/diacare.29.02.06.dc05-1593] [PMID: 16482699]
[http://dx.doi.org/10.2337/diacare.29.02.06.dc05-1593] [PMID: 16482699]
[12]
Pataky MW, Yu CS, Nie Y, et al. Skeletal muscle fiber type-selective effects of acute exercise on insulin-stimulated glucose uptake in insulin-resistant, high-fat-fed rats. Am J Physiol Endocrinol Metab 2019; 316(5): E695-706.
[http://dx.doi.org/10.1152/ajpendo.00482.2018] [PMID: 30753114]
[http://dx.doi.org/10.1152/ajpendo.00482.2018] [PMID: 30753114]
[13]
Morigny P, Houssier M, Mouisel E, Langin D. Adipocyte lipolysis and insulin resistance. Biochimie 2016; 125: 259-66.
[http://dx.doi.org/10.1016/j.biochi.2015.10.024] [PMID: 26542285]
[http://dx.doi.org/10.1016/j.biochi.2015.10.024] [PMID: 26542285]
[14]
Campbell JE, Drucker DJ. Islet α cells and glucagon-critical regulators of energy homeostasis. Nat Rev Endocrinol 2015; 11(6): 329-38.
[http://dx.doi.org/10.1038/nrendo.2015.51] [PMID: 25850661]
[http://dx.doi.org/10.1038/nrendo.2015.51] [PMID: 25850661]
[15]
Reinehr T. Type 2 diabetes mellitus in children and adolescents. World J Diabetes 2013; 4(6): 270-81.
[http://dx.doi.org/10.4239/wjd.v4.i6.270] [PMID: 24379917]
[http://dx.doi.org/10.4239/wjd.v4.i6.270] [PMID: 24379917]
[16]
Lankatillake C, Huynh T, Dias DA. Understanding glycaemic control and current approaches for screening antidiabetic natural products from evidence-based medicinal plants. Plant Methods 2019; 15(1): 105.
[http://dx.doi.org/10.1186/s13007-019-0487-8] [PMID: 31516543]
[http://dx.doi.org/10.1186/s13007-019-0487-8] [PMID: 31516543]
[17]
American Diabetes Association. (2) Classification and diagnosis of diabetes. Diabetes Care 2015; 38 (Suppl.): S8-S16.
[http://dx.doi.org/10.2337/dc15-S005] [PMID: 25537714]
[http://dx.doi.org/10.2337/dc15-S005] [PMID: 25537714]
[18]
Oniki K, Kawakami T, Nakashima A, et al. Melinjo seed extract increases adiponectin multimerization in physiological and pathological conditions. Sci Rep 2020; 10(1): 4313.
[http://dx.doi.org/10.1038/s41598-020-61148-2] [PMID: 32152335]
[http://dx.doi.org/10.1038/s41598-020-61148-2] [PMID: 32152335]
[19]
Huang DD, Shi G, Jiang Y, Yao C, Zhu C. A review on the potential of Resveratrol in prevention and therapy of diabetes and diabetic complications. Biomed Pharmacother 2020; 125109767
[http://dx.doi.org/10.1016/j.biopha.2019.109767] [PMID: 32058210]
[http://dx.doi.org/10.1016/j.biopha.2019.109767] [PMID: 32058210]
[20]
Critical Appraisal tools - Centre for evidence-based medicine (CEBM), University of Oxford. Available from: http://www.cebm.ox.ac.uk/resources/ebm-tools/critical-appraisal-tools (Accessed January 10, 2021).
[21]
Howard C. Subject and course guides: evidence based medicine: PICO. Available from: http://researchguides.uic.edu/c.php?g=252338&p=3954402 (Accessed January 10, 2021).
[22]
Rorsman P, Ashcroft FM. Pancreatic β-cell electrical activity and insulin secretion: Of mice and men. Physiol Rev 2018; 98(1): 117-214.
[http://dx.doi.org/10.1152/physrev.00008.2017] [PMID: 29212789]
[http://dx.doi.org/10.1152/physrev.00008.2017] [PMID: 29212789]
[23]
Boland BB, Rhodes CJ, Grimsby JS. The dynamic plasticity of insulin production in β-cells. Mol Metab 2017; 6(9): 958-73.
[http://dx.doi.org/10.1016/j.molmet.2017.04.010] [PMID: 28951821]
[http://dx.doi.org/10.1016/j.molmet.2017.04.010] [PMID: 28951821]
[24]
Bunney PE, Zink AN, Holm AA, Billington CJ, Kotz CM. Orexin activation counteracts decreases in nonexercise activity thermogenesis (NEAT) caused by high-fat diet. Physiol Behav 2017; 176: 139-48.
[http://dx.doi.org/10.1016/j.physbeh.2017.03.040] [PMID: 28363838]
[http://dx.doi.org/10.1016/j.physbeh.2017.03.040] [PMID: 28363838]
[25]
Flannick J, Florez JC. Type 2 diabetes: Genetic data sharing to advance complex disease research. Nat Rev Genet 2016; 17(9): 535-49.
[http://dx.doi.org/10.1038/nrg.2016.56] [PMID: 27402621]
[http://dx.doi.org/10.1038/nrg.2016.56] [PMID: 27402621]
[26]
Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet 2017; 389(10085): 2239-51.
[http://dx.doi.org/10.1016/S0140-6736(17)30058-2] [PMID: 28190580]
[http://dx.doi.org/10.1016/S0140-6736(17)30058-2] [PMID: 28190580]
[27]
Zhao H, Song A, Zhang Y, Shu L, Song G, Ma H. Effect of resveratrol on blood lipid levels in patients with type 2 diabetes: A systematic review and meta-analysis. Obesity (Silver Spring) 2019; 27(1): 94-102.
[http://dx.doi.org/10.1002/oby.22348] [PMID: 30569644]
[http://dx.doi.org/10.1002/oby.22348] [PMID: 30569644]
[28]
Bo S, Togliatto G, Gambino R, et al. Impact of sirtuin-1 expression on H3K56 acetylation and oxidative stress: A double-blind randomized controlled trial with resveratrol supplementation. Acta Diabetol 2018; 55(4): 331-40.
[http://dx.doi.org/10.1007/s00592-017-1097-4] [PMID: 29330620]
[http://dx.doi.org/10.1007/s00592-017-1097-4] [PMID: 29330620]
[29]
Sun X, Yu W, Hu C. Genetics of type 2 diabetes: Insights into the pathogenesis and its clinical application. BioMed Res Int 2014; 2014926713
[http://dx.doi.org/10.1155/2014/926713] [PMID: 24864266]
[http://dx.doi.org/10.1155/2014/926713] [PMID: 24864266]
[30]
Cho NH, Shaw JE, Karuranga S, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018; 138: 271-81.
[http://dx.doi.org/10.1016/j.diabres.2018.02.023] [PMID: 29496507]
[http://dx.doi.org/10.1016/j.diabres.2018.02.023] [PMID: 29496507]
[31]
Kaul N, Ali S. Genes, genetics, and environment in type 2 diabetes: Implication in personalized medicine. DNA Cell Biol 2016; 35(1): 1-12.
[http://dx.doi.org/10.1089/dna.2015.2883] [PMID: 26495765]
[http://dx.doi.org/10.1089/dna.2015.2883] [PMID: 26495765]
[32]
Lund A, Bagger JI, Christensen M, Knop FK, Vilsbøll T. Glucagon and type 2 diabetes: The return of the alpha cell. Curr Diab Rep 2014; 14(12): 555.
[http://dx.doi.org/10.1007/s11892-014-0555-4] [PMID: 25344790]
[http://dx.doi.org/10.1007/s11892-014-0555-4] [PMID: 25344790]
[33]
Irwin N, Flatt PR. New perspectives on exploitation of incretin peptides for the treatment of diabetes and related disorders. World J Diabetes 2015; 6(15): 1285-95.
[http://dx.doi.org/10.4239/wjd.v6.i15.1285] [PMID: 26557956]
[http://dx.doi.org/10.4239/wjd.v6.i15.1285] [PMID: 26557956]
[34]
Drucker DJ. Deciphering metabolic messages from the gut drives therapeutic innovation: The 2014 Banting Lecture. Diabetes 2015; 64(2): 317-26.
[http://dx.doi.org/10.2337/db14-1514] [PMID: 25614665]
[http://dx.doi.org/10.2337/db14-1514] [PMID: 25614665]
[35]
Vergès B. Pathophysiology of diabetic dyslipidaemia: Where are we? Diabetologia 2015; 58(5): 886-99.
[http://dx.doi.org/10.1007/s00125-015-3525-8] [PMID: 25725623]
[http://dx.doi.org/10.1007/s00125-015-3525-8] [PMID: 25725623]
[36]
Artasensi A, Pedretti A, Vistoli G, Fumagalli L. Type 2 diabetes mellitus: A review of multi-target drugs. Molecules 2020; 25(8): 1987.
[http://dx.doi.org/10.3390/molecules25081987] [PMID: 32340373]
[http://dx.doi.org/10.3390/molecules25081987] [PMID: 32340373]
[37]
Sharma S, Tripathi P. Gut microbiome and type 2 diabetes: Where we are and where to go? J Nutr Biochem 2019; 63: 101-8.
[http://dx.doi.org/10.1016/j.jnutbio.2018.10.003] [PMID: 30366260]
[http://dx.doi.org/10.1016/j.jnutbio.2018.10.003] [PMID: 30366260]
[38]
Goyal R, Jialal I. Diabetes mellitus type 2 Available from: https://www.ncbi.nlm.nih.gov/books/NBK513253/ (Accessed January 10, 2021).
[39]
Koeck P, Bastiaens H, Benhalima K, et al. Diabetes mellitus type 2. Available from: http://www.domusmedica.be/sites/default/files/Richtlijn%20Diabetes_0.pdf (Accessed January 10, 2021).
[40]
Sears B, Perry M. The role of fatty acids in insulin resistance. Lipids Health Dis 2015; 14(1): 121.
[http://dx.doi.org/10.1186/s12944-015-0123-1] [PMID: 26415887]
[http://dx.doi.org/10.1186/s12944-015-0123-1] [PMID: 26415887]
[41]
The Beginner’s Guide to Boolean Search Operators. Available from: https://www.socialtalent.com/blog/recruitment/the-beginners-guide-to-boolean-search-terms (Accessed January 10, 2021).
[42]
PICO - Evidence Based Medicine - Subject and Course Guides at University of Illinois at Chicago. Available from: http://researchguides.uic.edu/c.php?g=252338&p=3954402 (Accessed January 10, 2021).
[43]
Szkudelski T, Szkudelska K. Resveratrol and diabetes: From animal to human studies. Biochim Biophys Acta 2015; 1852(6): 1145-54.
[http://dx.doi.org/10.1016/j.bbadis.2014.10.013] [PMID: 25445538]
[http://dx.doi.org/10.1016/j.bbadis.2014.10.013] [PMID: 25445538]
[44]
Timmers S, de Ligt M, Phielix E, et al. Resveratrol as add-on therapy in subjects with well-controlled type 2 diabetes: A randomized controlled trial. Diabetes Care 2016; 39(12): 2211-7.
[http://dx.doi.org/10.2337/dc16-0499] [PMID: 27852684]
[http://dx.doi.org/10.2337/dc16-0499] [PMID: 27852684]
[45]
Seyyedebrahimi S, Khodabandehloo H, Nasli Esfahani E, Meshkani R. The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial. Acta Diabetol 2018; 55(4): 341-53.
[http://dx.doi.org/10.1007/s00592-017-1098-3] [PMID: 29357033]
[http://dx.doi.org/10.1007/s00592-017-1098-3] [PMID: 29357033]
[46]
Roden M, Shulman GI. The integrative biology of type 2 diabetes. Nature 2019; 576(7785): 51-60.
[http://dx.doi.org/10.1038/s41586-019-1797-8] [PMID: 31802013]
[http://dx.doi.org/10.1038/s41586-019-1797-8] [PMID: 31802013]
[47]
Lan F, Weikel KA, Cacicedo JM, Ido Y. Resveratrol-induced AMP-activated protein kinase activation is cell-type dependent: Lessons from basic research for clinical application. Nutrients 2017; 9(7): 751.
[http://dx.doi.org/10.3390/nu9070751] [PMID: 28708087]
[http://dx.doi.org/10.3390/nu9070751] [PMID: 28708087]
[48]
Moore T, Yanes RE, Calton MA, Vollrath D, Enns GM, Cowan TM. AMP-independent activator of AMPK for treatment of mitochondrial disorders. PLoS One 2020; 15(10)e0240517
[http://dx.doi.org/10.1371/journal.pone.0240517] [PMID: 33052980]
[http://dx.doi.org/10.1371/journal.pone.0240517] [PMID: 33052980]
[49]
Bellou V, Belbasis L, Tzoulaki I, Evangelou E. Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses. PLoS One 2018; 13(3)e0194127
[http://dx.doi.org/10.1371/journal.pone.0194127] [PMID: 29558518]
[http://dx.doi.org/10.1371/journal.pone.0194127] [PMID: 29558518]
[50]
Zhang T, He Q, Liu Y, Chen Z, Hu H. Efficacy and safety of resveratrol supplements on blood lipid and blood glucose control in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med 2021; 20215644171
[http://dx.doi.org/10.1155/2021/5644171] [PMID: 34484395]
[http://dx.doi.org/10.1155/2021/5644171] [PMID: 34484395]
[51]
Abdelhaleem IA, Brakat AM, Adayel HM, Asla MM, Rizk MA, Aboalfetoh AY. The effects of resveratrol on glycemic control and cardiometabolic parameters in patients with T2DM: A systematic review and meta-analysis Med Clin (Barc) 2021; S0025-7753(2): 00472-3 Epub ahead of print.
[http://dx.doi.org/10.1016/j.medcli.2021.06.028] [PMID: 34666902]
[http://dx.doi.org/10.1016/j.medcli.2021.06.028] [PMID: 34666902]
[52]
Ribeiro R, Santos AC, Calazans MO, De Oliveira ACP, Vieira LB. Is resveratrol a prospective therapeutic strategy in the co-association of glucose metabolism disorders and neurodegenerative diseases? Nutr Neurosci 2021; 1-16. Epub ahead of print
[http://dx.doi.org/10.1080/1028415X.2021.1972514] [PMID: 34514962]
[http://dx.doi.org/10.1080/1028415X.2021.1972514] [PMID: 34514962]
[53]
Cottart CH, Nivet-Antoine V, Laguillier-Morizot C, Beaudeux JL. Resveratrol bioavailability and toxicity in humans. Mol Nutr Food Res 2010; 54(1): 7-16.
[http://dx.doi.org/10.1002/mnfr.200900437] [PMID: 20013887]
[http://dx.doi.org/10.1002/mnfr.200900437] [PMID: 20013887]
[54]
Singh AP, Singh R, Verma SS, et al. Health benefits of resveratrol: Evidence from clinical studies. Med Res Rev 2019; 39(5): 1851-91.
[http://dx.doi.org/10.1002/med.21565] [PMID: 30741437]
[http://dx.doi.org/10.1002/med.21565] [PMID: 30741437]
[55]
Sangeetha MK, Vallabi DE, Sali VK, Thanka J, Vasanthi HR. Sub-acute toxicity profile of a modified resveratrol supplement. Food Chem Toxicol 2013; 59: 492-500.
[http://dx.doi.org/10.1016/j.fct.2013.06.037] [PMID: 23819915]
[http://dx.doi.org/10.1016/j.fct.2013.06.037] [PMID: 23819915]
Article Metrics
5