Skip to main content

Screening of Natural Antidiabetic Agents

  • Chapter
  • First Online:
Phytochemistry: An in-silico and in-vitro Update

Abstract

Diabetes mellitus (DM) is a metabolic disease characterized by a relative or absolute lack of insulin that leads to hyperglycaemia. Approximately two to five million cases of deaths result from diabetes each year. As of 2017, there are over 425 million sufferers of DM worldwide (representing over 8.3% of the adult population) and a projected increase to 629 million by the year 2045. Every year, millions of dollars are committed in the global health care and in research and development of effective antidiabetic medications. So far, tremendous progress has been made in the search for safer natural antidiabetic agents but more needs to be done because of the multifactorial nature of diabetes and its comorbidities. This chapter details the various methods involved in the screening of natural antidiabetic agents. It takes into account the various in silico tools, in vitro and animal models. The methods are presented in a clear and concise manner to aid easy adoption and replications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Allen RE, Hughes TD, Ng JL, Ortiz RD, Ghantous MA, Bouhali O, Frogue P, Arredouani A. Mechanisms behind the immediate effects of Roux-en-Y gastric bypass surgery on type 2 diabetes. Theor Biol Med Model. 2013;10(45):1–19.

    Google Scholar 

  • American Diabetes Association. Diabetes Care. 2015; 38(Supplement 1): S8-S16. https://doi.org/10.2337/dc15-S005. Available: http://care.diabetesjournals.org/content/38/Supplement_1/S8 Retrieved: 9th August, 2018.

  • Ansarullah BB, Dwivedi M, Laddha NC, Begum R, Hardikar AA, Ramachandran A. Antioxidant rich flavonoids from Oreocnide integrifolia enhance glucose uptake and insulin secretion and protects pancreatic β-cells from streptozotocin insult. BMC Complement Altern Med. 2011;11:126. https://doi.org/10.1186/1472-6882-11-126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asano T, Ogihara T, Katagiri H, Sakoda H, Ono H, Fujishiro M, Anai M, Kurihara H, Uchijima Y. Glucose transporter and Na+ / glucose cotransporter as molecular targets of anti-diabetic drugs. Curr Med Chem. 2004;11(20):2717–24.

    Article  CAS  PubMed  Google Scholar 

  • Basu A, Sohn YS, Alyan M, Nechushtai R, Domb AJ, Goldblum A. Discovering novel and diverse iron-chelators in silico. J Chem Inf Model. 2016;56:2476–85.

    Article  CAS  PubMed  Google Scholar 

  • Bergman RN, Ader M. Atypical antipsychotics and glucose homeostasis. J Clin Psychiatry. 2005;66:504–14.

    Article  CAS  PubMed  Google Scholar 

  • Brayer GD, Luo Y, Withers SG. The structure of human pancreatic α-amylase at 1.8 A resolution and comparisons with related enzymes. Protein Sci. 1995;4:1730–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cavarape A, Feletto F, Mercuri F, Quagliaro L, Damante G, Ceriello A. High-fructose diet decreases catalase mRNA levels in rat tissues. J Endocrinol Investig. 2001;24(11):838–45.

    Article  CAS  Google Scholar 

  • Chaudhury A, Duvoor C, Dendi VSR, Kraleti S, Chada A, Ravilla R, et al. Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management. Front Endocrinol. 2017;8(6):1–12. https://doi.org/10.3389/fendo.2017.00006.

    Article  Google Scholar 

  • Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus-present and future perspectives. Nat Rev Endocrinol. 2011;8(4):228–36.

    Article  PubMed  CAS  Google Scholar 

  • Choi SB, Park CH, Choi MK, Jun DW, Park S. Improvement of insulin resistance and insulin secreation by water extracts of Cordiceps militaris, phellinus linteus and paecilomyce tenuipes in 90% pancreatectomized rats. J Biotech Biochem. 2004;68:2257–64.

    Article  CAS  Google Scholar 

  • Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab. 2011;13:7–18.

    Article  CAS  PubMed  Google Scholar 

  • Defronzo RA. Banting lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DePaula AL, Macedo AL, Mota BR, Schraibman V. Laparoscopic ileal interposition associated to a diverted sleeve gastrectomy is an effective operation for the treatment of type 2 diabetes mellitus patients with BMI 21–29. Surg Endosc. 2009;23:1313–20.

    Article  CAS  PubMed  Google Scholar 

  • Dsouza D, Lakshmidev N. Models to study in vitro antidiabetic activity of plants: a review. Int J Pharm Bio Sci. 2015;6(3):732–41.

    Google Scholar 

  • Dunn JS, Sheehan HL, McLetchie NGB. Necrosis of islets of Langerhans produced experimentally. Lancet. 1943;241(6242):484–7. https://doi.org/10.1016/S0140-6736(00)42072-6.

    Article  Google Scholar 

  • Eleazu CO, Eleazu KC, Chukwuma S, Essien UN. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J Diabetes Metab Disord. 2013;12:60e67.

    Article  CAS  Google Scholar 

  • Epand RM, Stafford AR, Tyers M, Nieboer E. Mechanism of action of diabetogenic zinc chelating agents. Model Syst Stud Mol Pharmacol. 1985;27(3):366–74.

    CAS  Google Scholar 

  • Etuk EU. Animals models for studying diabetes mellitus. Agric Biol J N Am. 2010;1:130–4.

    CAS  Google Scholar 

  • Gallagher AM, Flatt PR, Duffy G, Abdelwahab YHA. The effects of traditional antidiabetic plants on in vitro glucose diffusion. Nutr Res. 2003;23(3):413–24.

    Article  CAS  Google Scholar 

  • Ganda OP, Rossini AA, Like AA. Studies on streptozotocin diabetes. Diabetes. 1976;25:596–603.

    Article  Google Scholar 

  • Garcia-Sosa AT, Maran U, Hetenyi C. Molecular property filters describing pharmacokinetics and drug binding. Curr Med Chem. 2012;19:1646–62.

    Article  CAS  PubMed  Google Scholar 

  • Gavin TP, Sloan RC, Lukosius EZ, et al. Duodenal-jejunal bypass surgery does not increase skeletal muscle insulin signal transduction or glucose disposal in Goto-Kakazaki type 2 diabetic rats. Obes Surg. 2011;21(2):231–7. https://doi.org/10.1007/s11695-010-0304-y.

    Article  PubMed  Google Scholar 

  • Gillespie EL, White CM, Kardas M, Lindberg M, Coleman CI. The impact of ACE inhibitors or angiotensin II type 1 receptor blockers on the development of new-onset type 2 diabetes. Diabetes Care. 2005;28(9):2261–5.

    Article  CAS  PubMed  Google Scholar 

  • Glick M, Goldblum A. A novel energy-based stochastic method for positioning polar protons in protein structures from X-rays. Proteins. 2000;38:273–87.

    Article  CAS  PubMed  Google Scholar 

  • Glick M, Rayan A, Goldblum A. A stochastic algorithm for global optimization and for best populations: a test case of side chains in proteins. Proc Natl Acad Sci. 2002;99:703–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gondi M, Prasada RU. Ethanol extract of mango (Mangifera indica L.) peel inhibits α-amylase and α-glucosidase activities, and ameliorates diabetes related biochemical parameters in streptozotocin (STZ)-induced diabetic rats. J Food Sci Technol Mysore. 2015;52(12):7883–93.

    Article  CAS  Google Scholar 

  • Goto Y, Kakizaki M. The spontaneous diabetes rat: a model of non insulin dependent diabetes mellitus. Proc Jpn Acad. 1981;57:381–4.

    Article  Google Scholar 

  • Goyal SN, Reddy NM, Patil KR, Nakhate KT, Ojha S, Patil CR, Agrawal YO. Challenges and issues with streptozotocin-induced diabetes – a clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics. Chem Biol Interact. 2016;244:49–63.

    Article  CAS  PubMed  Google Scholar 

  • Gustavsson C, Soga T, Wahlström E, Vesterlund M, Azimi A, et al. Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in zucker diabetic fatty rats. J Mol Endocrinol. 2011;47(2):129–43.

    Article  CAS  PubMed  Google Scholar 

  • Hao M, Zhang S, Qiu J. Toward the prediction of FBPase inhibitory activity using chemoinformatic methods. Int J Mol Sci. 2012;13:7015–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harbilas D, Martineau LC, Harris CS, Adeyiwolα-Spoor DCA, et al. Evaluation of the antidiabetic potential of selected medicinal plant extracts from the Canadian boreal forest used to treat symptoms of diabetes: part II. Can J Physiol Pharmacol. 2009;87:479–92.

    Article  CAS  PubMed  Google Scholar 

  • Haskell BD, Flurkey K, Duffy TM, Sargent EE, Leiter EH. The diabetes- prone NZO/H1Lt strain. I. Immunophenotypic comparison to the related NZB/B1NJ and NZW/LacJ strains. Lab Investig. 2002;82:833–42.

    Article  PubMed  Google Scholar 

  • Heikamp K, Bajorath J. Comparison of confirmed inactive and randomly selected compounds as negative training examples in support vector machine-based virtual screening. J Chem Inf Model. 2013;53:1595–601.

    Article  CAS  PubMed  Google Scholar 

  • Holt AIG, Peveler RC. Association between antipsychotic drugs and diabetes. Diabetes Obes Metab. 2006;8:125–35.

    Article  CAS  PubMed  Google Scholar 

  • Honda M, Hara Y. Inhibition of rat small intestinal sucrase and α-glucosidase activities by tea polyphenols. Biosci Biotechnol Biochem. 1993;57:123–4.

    Article  CAS  PubMed  Google Scholar 

  • Huang S, Czech MP. The GLUT4 glucose transporter. Cell Metab. 2007;5(4):237–52. https://doi.org/10.1016/j.cmet.2007.03.006.

    Article  CAS  PubMed  Google Scholar 

  • Hussain F, Arif M, Sheikh MA. Prevalence of diabetic retinopathy in Faisalabad, Pakistan: a population based study. Turk J Med Sci. 2011;41(4):735–42.

    Google Scholar 

  • Ighodaro OM, Adeosun AM, Akinloye OE. Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies. Medicina. 2017;53:365–74.

    Article  PubMed  Google Scholar 

  • im Walde SS, Dohle C, Schott-Ohly P, Gleichmann H. Molecular target structures in alloxan-induced diabetes in mice. Life Sci. 2002;71:1681–94.

    Article  PubMed  Google Scholar 

  • International Diabetes Federation. IDF diabetes atlas – 8th edition. Powerpoint presentation slide 3–4. 2017. Available: http://diabetesatlas.org/component/attachments/?task=download&id=271. Retrieved: 9th Aug 2018.

  • JeBailey L, Wanono O, Niu W, Roessler J, Rudich A, Klip A. Ceramide- and oxidant-induced insulin resistance involve loss of insulin-dependent Rac-activation and actin remodeling in muscle cells. Diabetes. 2007;56(2):394–403.

    Article  CAS  PubMed  Google Scholar 

  • Junod A, Lambert AE, Orci L, Pictet R, Gonet AE, et al. Studies of the diabetogenic action of streptozotocin. Proc Soc Exp Biol Med. 1967;126(1):201–5.

    Article  CAS  PubMed  Google Scholar 

  • Kahn SE. The importance of the beta-cell in the pathogenesis of type 2 diabetes mellitus. Am J Med. 2000;108(6a Suppl):2S–8S.

    Article  CAS  PubMed  Google Scholar 

  • Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C. Direct association of adenosine deaminase with a T cell activation antigen, CD26. Science. 1993;261(5120):466–9.

    Article  CAS  PubMed  Google Scholar 

  • Karasawa H, Takaishi K, Kumagae Y. Obesity-induced diabetes in mouse strains treated with gold thioglucose: a novel animal model for studying β-cell dysfunction. Obesity (Silver Spring, Md). 2011;19(3):514–21.

    Article  CAS  Google Scholar 

  • Kennedy BP. Role of protein tyrosine phosphatase-1B in diabetes and obesity. Biomed Pharmacother. 1999;53(10):466–70.

    Article  CAS  PubMed  Google Scholar 

  • Kerru N, Singh-Pillay A, Awolade P, Singh P. Current anti-diabetic agents and their molecular targets: a review. Eur J Med Chem. 2018;152:436–88.

    Article  CAS  PubMed  Google Scholar 

  • Kim HR, Rho HW, Park BH, Park JW, Kim JS, Kim UH, et al. Role of Ca2+ in alloxan-induced pancreatic beta-cell damage. Biochim Biophys Acta. 1994;1227:87–91.

    Article  CAS  PubMed  Google Scholar 

  • King AJ. The use of animal models in diabetes research. Br J Pharmacol. 2012;166:877–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knouff C, Auwerx J. Peroxisome proliferator-activated receptor –Î3 calls for activation in moderation: lessons from genetics and pharmacology. Endocr Rev. 2004;25(6):899–918.

    Article  CAS  PubMed  Google Scholar 

  • Ktorza A, Bernard C, Parent V, Penicaud L, Froguel P, et al. Are animal models of diabetes relevant to the study of the genetics of noninsulin-dependent diabetes in humans? Diabetes Metab. 1997;23(Suppl 2):38–46.

    PubMed  Google Scholar 

  • Kwon YI, Vattem DV, Shetty K. Evaluation of clonal herbs of Lamiaceae species for management of diabetes and hypertension. Asia Pac J Clin Nutr. 2006;15:107–18.

    PubMed  Google Scholar 

  • Lenzen S. The mechanisms of alloxan-and streptozotocin-induced diabetes. Diabetologia. 2008;51:216e226.

    Article  CAS  Google Scholar 

  • Lusci A, Pollastri G, Baldi P. Deep architectures and deep learning in chemoinformatics: the prediction of aqueous solubility for drug-like molecules. J Chem Inf Model. 2013;53:1563–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malaisse WJ, Malaisse-Lagae F, Sener A, Pipeleers DG. Determinants of the selective toxicity of alloxan to the pancreatic β cell. Proc Natl Acad Sci U S A. 1982;79:927–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malhotra A, Penpargkul S, Fein FS, Sonnenblick EH, Scheuer J. The effect of streptozotocin induced diabetes in rats on cardiac contractile proteins. Circ Res. 1981;49(6):1243–50.

    Article  CAS  PubMed  Google Scholar 

  • Manikandan R, Anand AV, Kumar S, Pushpa. Phytochemical and in vitro antidiabetic activity of Psidium Guajava leaves. Pharm J. 2016;8(4):392–4.

    CAS  Google Scholar 

  • Masiello P. Animal models of type11 diabetes with reduced pancreatic β-cell mass. Int J Biochem Cell Biol. 2006;38:873–93.

    Article  CAS  PubMed  Google Scholar 

  • Mathews CE, Leiter EH. Constitutive differences in antioxidant defense status distinguish alloxan-resistant and alloxan-susceptible mice. Free Radic Biol Med. 1999;27:449–55.

    Article  CAS  PubMed  Google Scholar 

  • McIntosh CHS, Pederson RA. Non-insulin dependent animal models of diabetes mellitus. In: McNeil JH, editor. Experimental models of diabetes. Boca Raton: CRC Press LLC; 1999. p. 337–98.

    Google Scholar 

  • McNeil JH. Experimental models of diabetes. Boca Raton: CRC Press LLC; 1999.

    Google Scholar 

  • Mendez JD, Ramos HG. Animal models in diabetes research. Arch Med Res. 1994;25(4):367–75.

    CAS  PubMed  Google Scholar 

  • Miralles F, Portha B. Early development of beta cells is impaired in the GK rat model of type 2 diabetes. Diabetes. 2001;50:S84–8.

    Article  CAS  PubMed  Google Scholar 

  • Momose K, Nunomiya S, Nakata M, Yada T, Kikuchi M, et al. Immunohistochemical and electron-microscopic observation of β-cells in pancreatic islets of spontaneously diabetic Goto-Kakizaki rats. Med Mol Morphol. 2006;39(3):146–53.

    Article  PubMed  Google Scholar 

  • Mordes JP, Guberski DL, Leif JH, Woda BA, Flanagan JF, et al. LEW.1WR1 rats develop autoimmune diabetes spontaneously and in response to environmental perturbation. Diabetes. 2005;54(9):2727–33.

    Article  CAS  PubMed  Google Scholar 

  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.

    Article  CAS  PubMed  Google Scholar 

  • Motyl K, McCabe LR. Streptozotocin, type I diabetes severity and bone. Biol Proced Online. 2009;11:296–315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nerup J, Mandrup-Poulsen T, Helqvist S, Andersen HU, Pociot F, Reimers JI, et al. On the pathogenesis of IDDM. Diabetologia. 1994;37(Suppl. 2):S82–9.

    Article  PubMed  Google Scholar 

  • Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19(Suppl 1):1–93.

    CAS  PubMed  Google Scholar 

  • Nuss JM, Wagman AS. Recent advances in therapeutic approaches to type2 diabetes. Annu Rep Med Chem. 2000;35:211–20.

    CAS  Google Scholar 

  • Ozturk Y, Altan VM, Yildizoğlu-Ari N. Effects of experimental diabetes and insulin on smooth muscle functions. Pharmacol Rev. 1999;48:69–112.

    Google Scholar 

  • Parekh PI, Petro AE, Tiller JM, Feinglos MN, Surwit RS. Reversal of diet-induced obesity and diabetes in C57BL/6J mice. Metabolism. 1998;47(9):1089–96.

    Article  CAS  PubMed  Google Scholar 

  • Pechhold K, Patterson NB, Blum C, Fleischacker CL, Boehm BO, Harlan DM. Low dose streptozotocin-induced diabetes in rat insulin promoter-mCD80-transgenic mice is T cell autoantigen-specific and CD28 dependent. J Immunol. 2001;166:2531–9.

    Article  CAS  PubMed  Google Scholar 

  • Rayan A, Noy E, Chema D, Levitzki A, Goldblum A. Stochastic algorithm for kinase homology model construction. Curr Med Chem. 2004;11:675–92.

    Article  CAS  PubMed  Google Scholar 

  • Rayan A, Falah M, Raiyn J, Mawassi H, Raiyn N. Assessing drugs for their cardio-toxicity. Lett Drug Des Discov. 2010;7:409–14.

    Article  CAS  Google Scholar 

  • Rayan A, Falah M, Raiyn J, Da’adoosh B, Kadan S, Zaid H, Goldblum A. Indexing molecules for their hERG liability. Eur J Med Chem. 2013;65:304–14.

    Article  CAS  PubMed  Google Scholar 

  • Reddi AS, Camerini-Davalos RA. Hereditary diabetes in the KK mouse: an overview. Adv Exp Med Biol. 1988;246:7–15.

    Article  CAS  PubMed  Google Scholar 

  • Rees DA, Alcolado JC. Animal models of diabetes mellitus. Diabet Med. 2005;22:359–70.

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues R. A comprehensive review: the use of animal models in diabetes research. J Anal Pharm Res. 2016;3(5):1–5.

    Google Scholar 

  • Saidu Y, Muhammad SA, Abbas AY, Onu A, Tsado IM, Muhammad L. In vitro screening for protein tyrosine phosphatase 1B and dipeptidyl peptidase IV inhibitors from selected Nigerian medicinal plants. J Intercult Ethnopharmacol. 2017;6(2):154–7. https://doi.org/10.5455/jice.20161219011346.

    Article  CAS  PubMed  Google Scholar 

  • Sasaki S, et al. Intra peritoneally implanted artificial pancrease with trans karyotic beta-cells on micro carrier beads in a diffusion chamber improve hyperglycemia after 90%pancreatectomy in rats. In Vivo. 2000;14:535–41.

    CAS  PubMed  Google Scholar 

  • Sattar NA, Hussain F, Iqbal T, Sheikh MA. Determination of in vitro antidiabetic effects of Zingiber officinale Roscoe. Braz J Pharm Sci. 2012;48(4):601–7.

    Article  Google Scholar 

  • Scheen AJ, De Hert M. Risque de diabète sucré sous antipsychotiques atypiques. Med Hyg (Geneve). 2004;62:1591–6.

    Google Scholar 

  • Scheen AJ, De Hert M. Abnormal glucose metabolism in patients treated with antipsychotics. Diabetes Metab. 2007;33:169–75.

    Article  CAS  PubMed  Google Scholar 

  • Schuller A, Schneider G. Identification of hits and lead structure candidates with limited resources by adaptive optimization. J Chem Inf Model. 2008;48:1473–91.

    Article  PubMed  CAS  Google Scholar 

  • Selim SA, Selim AO. Effect of streptozotocin-induced diabetes mellitus on the. Egypt J Histol. 2013;36:103–13.

    Article  Google Scholar 

  • Shafrir E. Diabetes in animals: contribution to the understanding of diabetes by study of its etiopathology in animal models. In: Porte D, Sherwin RS, Baron A, editors. Diabetes mellitus. New York: McGraw-Hill; 2003. p. 231–55.

    Google Scholar 

  • Shahaf N, Pappalardo M, Basile L, Guccione S, Rayan A. How to choose the suitable template for homology modelling of GPCRs: 5-HT7 receptor as a test case. Mol Inform. 2016;35:414–23.

    Article  CAS  PubMed  Google Scholar 

  • Shori AB. Screening of antidiabetic and antioxidant activities of medicinal plants. J Integr Med. 2015;13(5):297–305.

    Article  PubMed  Google Scholar 

  • Srinivasan K, Ramarao P. Animal models in type 2 diabetes research an overview. Indian J Med Res. 2007;125:451–72.

    CAS  PubMed  Google Scholar 

  • Sylow L, Kleinert M, Pehmøller C, Prats C, Chiu TT, Klip A, Richter EA, Jensen TE. Akt and Rac1 signaling are jointly required for insulin-stimulated glucose uptake in skeletal muscle and downregulated in insulin resistance. Cell Signal. 2014;26(2):323–31.

    Article  CAS  PubMed  Google Scholar 

  • Szkudelski T. The mechanism of alloxan and streptozotocin action in β cells of the rat pancreas. Physiol Res. 2001;50:537–46.

    CAS  PubMed  Google Scholar 

  • Thatte U. Still in search of herbal medicine. Indian J Pharm. 2009;41:1–3.

    Article  Google Scholar 

  • Tripathi V, Verma J. Different models used to induce diabetes a comprehensive review. Int J Pharm Pharm Sci. 2014;6:29–32.

    Google Scholar 

  • Umezawa K, Kawakami M, Watanabe T. Molecular design and biological activities of protein tyrosine phosphatase inhibitors. Pharmacol Ther. 2003;99:15–24.

    Article  CAS  PubMed  Google Scholar 

  • Varmaan V, Rani Y, Avupati V. In silico based virtual screening for bioactive PPAR-y agonists. Indo Am J Pharm Sci. 2016;3(10):1237–75.

    CAS  Google Scholar 

  • Vavra JJ, Deboer C, Dietz A, Hanka LJ, Sokolski WT. Streptozotocin, a new antibacterial antibiotic. Antibiot Annu. 1959;7:230–5.

    PubMed  Google Scholar 

  • Vogel HG, Vogel WH. Drug discovery and evaluation; pharmacological assays. Heidelberg/Berlin: Springer; 1997.

    Book  Google Scholar 

  • Wang Q, Khayata Z, Kishib K, Ebinab Y, Klipa A. GLUT4 translocation by insulin in intact muscle cells: detection by a fast and quantitative assay. FEBS Lett. 1998;427(2):193–7.

    Article  CAS  PubMed  Google Scholar 

  • Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011;17(4):448–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • WHO. Global Health Estimates (GHE), 2000–2015 estimates. Geneva: World Health Organization; 2017. Available: http://www.who.int/mediacentre/factsheets/fs312/en/. Accessed on 26 July 2018.

    Google Scholar 

  • Winzell MS, Ahrén B. The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes. 2004;53(Suppl 3):S215–9.

    Article  PubMed  Google Scholar 

  • Wu KK, Huan Y. Streptozotocin-induced diabetic models in mice and rats. Curr Protoc Pharmacol. 2008;5:47.. 41–45.47. 14

    PubMed  Google Scholar 

  • Wu J, Yan L. Streptozotocin-induced type 1 diabetes in rodents as a model for studying.pdf>. Diabetes, Metab Syndr Obes Targets Ther Diabetes, Metab Syndr Obes: Targets Ther. 2015;8:181–8.

    CAS  Google Scholar 

  • Yang H, Fan S, Song D, Wang Z, Ma S, Li S, Li X, Xu M, Xu M, Wang X. Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress. Mol Med Rep. 2013;7(2):431–40.

    Article  CAS  PubMed  Google Scholar 

  • Zaid H, Talior-Volodarsky I, Antonescu C, Liu Z, Klip A. GAPDH binds GLUT4 reciprocally to hexokinase-II and regulates glucose transport activity. Biochem J. 2009;419(2):475–84.

    Article  CAS  PubMed  Google Scholar 

  • Zatsepin M, Mattes A, Rupp S, Finkelmeier D, Basu A, Burger-Kentischer A, Goldblum A. Computational discovery and experimental confirmation of TLR9 receptor antagonist leads. J Chem Inf Model. 2016;56:1835–46.

    Article  CAS  PubMed  Google Scholar 

  • Zeidan M, Rayan M, Zeidan N, Falah M, Rayan A. Indexing natural products for their potential anti-diabetic activity: filtering and mapping discriminative physicochemical properties. Molecules. 2017;22(9):1563.

    Article  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chukwuebuka Egbuna .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Egbuna, C. et al. (2019). Screening of Natural Antidiabetic Agents. In: Kumar, S., Egbuna, C. (eds) Phytochemistry: An in-silico and in-vitro Update. Springer, Singapore. https://doi.org/10.1007/978-981-13-6920-9_11

Download citation

Publish with us

Policies and ethics