Skip to main content

Advertisement

Log in

Proteins and bioactive peptides

Mechanisms of action on diabetes management

  • Review
  • Published:
Nutrafoods

Abstract

Type 2 diabetes mellitus (T2DM) is a major metabolic, multi-causal and heterogeneous disorder, characterised by chronic hyperglycaemia, which causes significant morbidity and mortality, with a considerable burden on health-care resources. The number of deaths due to T2DM highlights the importance of controlling the disease and its complications. It has been demonstrated that some proteins, protein hydrolysates, bioactive peptides and amino acids can control glucose levels directly or indirectly. Bioactive peptides have been identified in a range of food ingredients and offer the potential for incorporation into functional and nutraceutical foods. In this review, we discuss the possible mechanisms by which these compounds exert their action on glucose control such as modulating insulin production, incretin secretion, dipeptidyl peptidase-4 inhibition, regulation of glucose uptake in peripheral tissue and inhibition of some enzymes related with glucose absorption. Peptides such as IPAVF, PGVGGPLGPIGPCYE, CAYQWQRPVNRIR, PACGGFYISGRPG, WV, GPAE, GPGA, LP, IP, KLPGF and LI have shown potential for regulating blood glucose. Bioavailability and delivery of bioactive peptides are also discussed.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kankeu HT, Saksena P, Xu K, Evans DB (2013) The financial burden from non-communicable diseases in low- and middle-income countries: a literature review. Health Res Policy Syst 11:31

    Article  Google Scholar 

  2. Rochette L, Zeller M, Cottin Y, Vergely C (2014) Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta 1840(9):2709–2729

    Article  CAS  Google Scholar 

  3. Weir GC, Bonner-Weir S (2004) Five stages of evolving betacell dysfunction during progression to diabetes. Diabetes 53[Suppl 3]:S16–21

    Article  Google Scholar 

  4. Foster-Powell K, Barclay A, Brand-Miller J (2009) Glycemic health, type 2 diabetes, and functional foods. In: Pasupuleti VK, Anderson JW (eds) Nutraceuticals, glycemic health and type 2 diabetes. Wiley-Blackwell, Ames, IA, pp 87–95

    Chapter  Google Scholar 

  5. Korhonen H, Pihlanto A (2003) Food-derived bioactive peptides—opportunities for designing future foods. Curr Pharm Des 9(16):1297–1308

    Article  CAS  Google Scholar 

  6. Liljeberg Elmstahl H, Bjorck I (2001) Milk as a supplement to mixed meals may elevate postprandial insulinaemia. Eur J Clin Nutr 55(11):994–999

    Article  CAS  Google Scholar 

  7. Segura-Campos M, Chel-Guerrero L, Betancur-Ancona D, Hernandez-Escalante VM (2011) Bioavailability of bioactive peptides. Food Rev Int 27(3):213–226

    Article  CAS  Google Scholar 

  8. Shimizu M, Tsunogai M, Arai S (1997) Transepithelial transport of oligopeptides in the human intestinal cell, Caco-2. Peptides 18(5):681–687

    Article  CAS  Google Scholar 

  9. Rubio-Aliaga I, Daniel H (2002) Mammalian peptide transporters as targets for drug delivery. Trends Pharmacol Sci 23(9):434–440

    Article  CAS  Google Scholar 

  10. Daniel H (2004) Molecular and integrative physiology of intestinal peptide transport. Annu Rev Physiol 66(1):361–388

    Article  CAS  Google Scholar 

  11. Geissler S, Zwarg M, Knütter I, Markwardt F, Brandsch M (2010) The bioactive dipeptide anserine is transported by human proton-coupled peptide transporters. FEBS J 277(3):790–795

    Article  CAS  Google Scholar 

  12. Dantzig AH, Hoskins J, Tabas LB, Bright S, Shepard RL, Jenkins IL, Duckworth DC, Sportsman JR, Mackensen D, Rosteck PR, Skatrud PL (1994) Association of intestinal peptide-transport with a protein related to the cadherin superfamily. Science 264(5157):430–433

    Article  CAS  Google Scholar 

  13. Lindley DJ, Carl SM, Herrera-Ruiz D, Pan LF, Karpes LB, Goole JME, Gudmundsson OS, Knipp GT (2011) Drug transporters and their role in absorption and disposition of peptides and peptide-based pharmaceuticals. In: Li X, Hu M (eds) Oral bioavailability. Wiley, Hoboken, NJ, pp 291–308

    Chapter  Google Scholar 

  14. Fernández-Musoles R, Salom JB, Castelló-Ruiz M, Contreras MdM, Recio I, Manzanares P (2013) Bioavailability of antihypertensive lactoferricin B-derived peptides: transepithelial transport and resistance to intestinal and plasma peptidases. Int Dairy J 32(2):169–174

    Article  Google Scholar 

  15. Quirós A, Dávalos A, Lasunción MA, Ramos M, Recio I (2008) Bioavailability of the antihypertensive peptide LHLPLP: transepithelial flux of HLPLP. Int Dairy J 18(3):279–286

    Article  Google Scholar 

  16. Vermeirssen V, Van Camp J, Verstraete W (2004) Bioavailability of angiotensin I converting enzyme inhibitory peptides. Br J Nutr 92(3):357–366

    Article  CAS  Google Scholar 

  17. Gaudel C, Nongonierma AB, Maher S, Flynn S, Krause M, Murray BA, Kelly PM, Baird AW, FitzGerald RJ, Newsholme P (2013) A whey protein hydrolysate promotes insulinotropic activity in a clonal pancreatic beta-cell line and enhances glycemic function in ob/ob mice. J Nutr 143(7):1109–1114

    Article  CAS  Google Scholar 

  18. Osadebe PO, Odoh EU, Uzor PF (2015) Oral anti-diabetic agents-review and updates. Br J Med Med Res 5(2):134–159

    Article  Google Scholar 

  19. Ley SH, Hamdy O, Mohan V, Hu FB (2014) Prevention and management of type 2 diabetes: dietary components and nutritional strategies. Lancet 383(9933):1999–2007

    Article  CAS  Google Scholar 

  20. Amer Diabet A (2014) Standards of Medical Care in Diabetes — 2014. Diabetes Care 37:S14–S80

    Article  Google Scholar 

  21. Mann JI, De Leeuw I, Hermansen K, Karamanos B, Karlström B, Katsilambros N, Riccardi G, Rivellese AA, Rizkalla S, Slama G, Toeller M, Uusitupa M, Vessby B (2004) Evidence-based nutritional approaches to the treatment and prevention of diabetes mellitus. Nutr Metab Cardiovasc Dis 14(6), 373–394

    Article  CAS  Google Scholar 

  22. van de Laar FA (2008) Alpha-glucosidase inhibitors in the early treatment of type 2 diabetes. Vasc Health Risk Manag 4(6):1189–1195

    Google Scholar 

  23. Matsui T, Yoshimoto C, Osajima K, Oki T, Osajima Y (1996) In vitro survey of alpha-glucosidase inhibitory food components. Biosci Biotechnol Biochem 60(12):2019–2022

    Article  CAS  Google Scholar 

  24. Yu Z, Yin Y, Zhao W, Liu J, Chen F (2012) Anti-diabetic activity peptides from albumin against alpha-glucosidase and alpha-amylase. Food Chem 135(3):2078–2085

    Article  CAS  Google Scholar 

  25. Yu Z, Yin Y, Zhao W, Yu Y, Liu B, Liu J, Chen F (2011) Novel peptides derived from egg white protein inhibiting alpha-glucosidase. Food Chem 129(4):1376–1382

    Article  CAS  Google Scholar 

  26. Lee HJ, Lee H-S, Choi JW, Ra KS, Kim J-M, Suh HJ (2011) Novel tripeptides with α-glucosidase inhibitory activity isolated from silk cocoon hydrolysate. J Agric Food Chem 59(21):11522–11525

    Article  CAS  Google Scholar 

  27. Dolečková-Marešová L, Pavlik M, Horn M, Mares M (2005) De novo design of alpha-amylase inhibitor: a small linear mimetic of macromolecular proteinaceous ligands. Chem Biol 12(12):1349–1357

    Article  Google Scholar 

  28. van Loon LJ, Kruijshoop M, Menheere PP, Wagenmakers AJ, Saris WH, Keizer HA (2003) Amino acid ingestion strongly enhances insulin secretion in patients with longterm type 2 diabetes. Diabetes Care 26(3):625–630

    Article  Google Scholar 

  29. Newsholme P, Brennan L, Bender K (2006) Amino acid metabolism, β-cell function, and diabetes. Diabetes 55[Suppl 2]:S39–S47

    Article  Google Scholar 

  30. Gunnerud UJ, Ostman EM, Bjorck IME (2013) Effects of whey proteins on glycaemia and insulinaemia to an oral glucose load in healthy adults; a dose-response study. Eur J Clin Nutr 67(7):749–753

    Article  CAS  Google Scholar 

  31. Nongonierma AB, Gaudel C, Murray BA, Flynn S, Kelly PM, Newsholme P, FitzGerald RJ (2013) Insulinotropic properties of whey protein hydrolysates and impact of peptide fractionation on insulinotropic response. Int Dairy J 32(2):163–168

    Article  CAS  Google Scholar 

  32. Manders RJF, Hansen D, Zorenc AHG, Dendale P, Kloek J, Saris WHM, van Loon LJC (2014) Protein co-ingestion strongly increases postprandial insulin secretion in type 2 diabetes patients. J Med Food 17(7):758–763

    Article  CAS  Google Scholar 

  33. Nauck MA (2011) Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications. Am J Med 124[1 Suppl]:S3–18

    Article  Google Scholar 

  34. Nauck MA, Meier JJ (2010) Individualised incretin-based treatment for type 2 diabetes. Lancet 376(9739):393–394

    Article  Google Scholar 

  35. Yabe D, Seino Y (2011) Two incretin hormones GLP-1 and GIP: comparison of their actions in insulin secretion and beta cell preservation. Prog Biophys Mol Biol 107(2):248–256

    Article  CAS  Google Scholar 

  36. Nilsson M, Holst JJ, Bjorck IM (2007) Metabolic effects of amino acid mixtures and whey protein in healthy subjects: studies using glucose-equivalent drinks. Am J Clin Nutr 85(4):996–1004

    CAS  Google Scholar 

  37. Jakubowicz D, Froy O, Ahren B, Boaz M, Landau Z, Bar-Dayan Y, Ganz T, Barnea M, Wainstein J (2014) Incretin, insulinotropic and glucose-lowering effects of whey protein pre-load in type 2 diabetes: a randomised clinical trial. Diabetologia 57(9):1807–1811

    Article  CAS  Google Scholar 

  38. Higuchi N, Hira T, Yamada N, Hara H (2013) Oral administration of corn zein hydrolysate stimulates GLP-1 and GIP secretion and improves glucose tolerance in male normal rats and Goto-Kakizaki rats. Endocrinology 154(9):3089–3098

    Article  CAS  Google Scholar 

  39. Zhang J, Xue C, Zhu T, Vivekanandan A, Pennathur S, Ma ZA, Chen YE (2013) A tripeptide diapin effectively lowers bood glucose levels in male type 2 diabetes mice by increasing blood levels of insulin and GLP-1. PLos One 8(12)

    Google Scholar 

  40. Le Neve B, Daniel H (2011) Selected tetrapeptides lead to a GLP-1 release from the human enteroendocrine cell line NCI-H716. Regul Peptides 167(1):14–20

    Article  Google Scholar 

  41. Gallego M, Aristoy MC, Toldra F (2014) Dipeptidyl peptidase IV inhibitory peptides generated in Spanish dry-cured ham. Meat Sci 96(2 Pt A):757–761

    Article  CAS  Google Scholar 

  42. Lacroix IME, Li-Chan ECY (2012) Dipeptidyl peptidase-IV inhibitory activity of dairy protein hydrolysates. Int Dairy J 25(2):97–102

    Article  CAS  Google Scholar 

  43. Nongonierma AB, FitzGerald RJ (2013) Dipeptidyl peptidase IV inhibitory and antioxidative properties of milk proteinderived dipeptides and hydrolysates. Peptides 39:157–163

    Article  CAS  Google Scholar 

  44. Uenishi H, Kabuki T, Seto Y, Serizawa A, Nakajima H (2012) Isolation and identification of casein-derived dipeptidylpeptidase 4 (DPP-4)-inhibitory peptide LPQNIPPL from gouda-type cheese and its effect on plasma glucose in rats. Int Dairy J 22(1):24–30

    Article  CAS  Google Scholar 

  45. Estrada-Salas PA, Montero-Moran GM, Martinez-Cuevas PP, Gonzalez C, Barba de la Rosa AP (2014) Characterization of antidiabetic and antihypertensive properties of canary seed (Phalaris canariensis L.) peptides. J Agric Food Chem 62(2):427–433

    Article  CAS  Google Scholar 

  46. Velarde-Salcedo AJ, Barrera-Pacheco A, Lara-Gonzalez S, Montero-Moran GM, Diaz-Gois A, Gonzalez de Mejia E, Barba de la Rosa AP (2013) In vitro inhibition of dipeptidyl peptidase IV by peptides derived from the hydrolysis of amaranth (Amaranthus hypochondriacus L.) proteins. Food Chem 136(2):758–764

    Article  CAS  Google Scholar 

  47. Olson AL (2012) Regulation of GLUT4 and insulin-dependent glucose flux. Mol Biol 2012:12

    Google Scholar 

  48. Shulman GI (2000) Cellular mechanisms of insulin resistance. J Clin Invest 106(2):171–176

    Article  CAS  Google Scholar 

  49. Han D-N, Zhang D-H, Wang L-P, Zhang Y-S (2013) Protective effect of β-casomorphin-7 on cardiomyopathy of streptozotocin-induced diabetic rats via inhibition of hyperglycemia and oxidative stress. Peptides 44:120–126

    Article  CAS  Google Scholar 

  50. Morato PN, Lollo PCB, Moura CS, Batista TM, Camargo RL, Carneiro EM, Amaya-Farfan J (2013) Whey protein hydrolysate increases translocation of GLUT-4 to the plasma membrane independent of insulin in Wistar rats. PLoS One 8(8):7

    Article  Google Scholar 

  51. Morato PN, Lollo PC, Moura CS, Batista TM, Carneiro EM, Amaya-Farfan J (2013) A dipeptide and an amino acid present in whey protein hydrolysate increase translocation of GLUT-4 to the plasma membrane in Wistar rats. Food Chem 139(1–4):853–859

    Article  CAS  Google Scholar 

  52. Lee H-S, Lee HJ, Suh HJ (2011) Silk protein hydrolysate increases glucose uptake through up-regulation of GLUT 4 and reduces the expression of leptin in 3T3-L1 fibroblast. Nutr Res 31(12):937–943

    Article  CAS  Google Scholar 

  53. Lu J, Zeng Y, Hou W, Zhang S, Li L, Luo X, Xi W, Chen Z, Xiang M (2012) The soybean peptide aglycin regulates glucose homeostasis in type 2 diabetic mice via IR/IRS1 pathway. J Nutr Biochem 23(11):1449–1457

    Article  CAS  Google Scholar 

  54. Cavazos A, Gonzalez de Mejia E (2013). Identification of bioactive peptides from cereal storage proteins and their potential role in prevention of chronic diseases. Comprehen Rev Food Sci Food Safety 12(4):364–380

    Article  CAS  Google Scholar 

  55. Silveira ST, Martínez-Maqueda D, Recio I, Hernández-Ledesma B (2013) Dipeptidyl peptidase-IV inhibitory peptides generated by tryptic hydrolysis of a whey protein concentrate rich in β-lactoglobulin. Food Chem 141(2):1072–1077

    Article  CAS  Google Scholar 

  56. Lacroix IME, Li-Chan ECY (2013) Inhibition of dipeptidyl peptidase (DPP)-IV and α-glucosidase activities by pepsintreated whey proteins. J Agric Food Chem 61(31):7500–7506

    Article  CAS  Google Scholar 

  57. Huang S-L, Jao C-L, Ho K-P, Hsu K-C (2012) Dipeptidylpeptidase IV inhibitory activity of peptides derived from tuna cooking juice hydrolysates. Peptides 35(1):114–121

    Article  CAS  Google Scholar 

  58. Li-Chan ECY, Hunag S-L, Jao C-L, Ho K-P, Hsu K-C (2012) Peptides derived from Atlantic salmon skin gelatin as dipeptidyl-peptidase IV inhibitors. J Agric Food Chem 60(4):973–978

    Article  CAS  Google Scholar 

  59. Hatanaka T, Inoue Y, Arima J, Kumagai Y, Usuki H, Kawakami K, Kimura M, Mukaihara T (2012) Production of dipeptidyl peptidase IV inhibitory peptides from defatted rice bran. Food Chem 134(2):797–802

    Article  CAS  Google Scholar 

  60. Roblet C, Doyen A, Amiot J, Pilon G, Marette A, Bazinet L (2014) Enhancement of glucose uptake in muscular cell by soybean charged peptides isolated by electrodialysis with ultrafiltration membranes (EDUF): activation of the AMPK pathway. Food Chem 147:124–130

    Article  CAS  Google Scholar 

  61. Doyen A, Udenigwe CC, Mitchell PL, Marette A, Aluko RE, Bazinet L (2014) Anti-diabetic and antihypertensive activities of two flaxseed protein hydrolysate fractions revealed following their simultaneous separation by electrodialysis with ultrafiltration membranes. Food Chem 145:66–76

    Article  CAS  Google Scholar 

  62. Zhu C-F, Peng H-B, Liu G-Q, Zhang F, Li Y (2010) Beneficial effects of oligopeptides from marine salmon skin in a rat model of type 2 diabetes. Nutrition 26(10):1014–1020

    Article  CAS  Google Scholar 

  63. Samocha-Bonet D, Wong O, Synnott EL, Piyaratna N, Douglas A, Gribble FM, Holst JJ, Chisholm DJ, Greenfield JR (2011) Glutamine reduces postprandial glycemia and augments the glucagon-like peptide-1 response in type 2 diabetes patients. J Nutr 141(7):1233–1238

    Article  CAS  Google Scholar 

  64. Greenfield JR, Farooqi IS, Keogh JM, Henning E, Habib AM, Blackwood A, Reimann F, Holst JJ, Gribble FM (2009) Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. Am J Clin Nutr 89(1):106–113

    Article  CAS  Google Scholar 

  65. Kalogeropoulo D, LaFave L, Schweim K, Gannon MC, Nuttall FQ (2008) Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose. Metabolism 57(12):1747–1752

    Article  Google Scholar 

  66. Manders RJF, Praet SFE, Meex RCR, Koopman R, de Roos AL, Wagenmakers AJM, Saris WHM, van Loon LJC (2006) Protein hydrolysate/leucine co-ingestion reduces the prevalence of hyperglycemia in type 2 diabetic patients. Diabetes Care 29(12):2721–2722

    Article  CAS  Google Scholar 

  67. Meric E, Lemieux S, Turgeon SL, Bazinet L (2014) Insulin and glucose responses after ingestion of different loads and forms of vegetable or animal proteins in protein enriched fruit beverages. J Funct Food 10:95–103

    Article  CAS  Google Scholar 

  68. Goudarzi M, Madadlou A (2013) Influence of whey protein and its hydrolysate on prehypertension and postprandial hyperglycaemia in adult men. Int Dairy J 33(1):62–66

    Article  CAS  Google Scholar 

  69. Karamanlis A, Chaikornin R, Doran S, Bellon M, Bartholomeusz FD, Wishart JM, Jones KL, Horowitz M, Rayner CK (2007) Effects of protein on glycemic and incretin responses and gastric emptying after oral glucose in healthy subjects. Am J Clin Nutr 86(5):1364–1368

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Silvia L. Amaya-Llano.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oseguera-Toledo, M.E., González de Mejía, E., Reynoso-Camacho, R. et al. Proteins and bioactive peptides. Nutrafoods 13, 147–157 (2014). https://doi.org/10.1007/s13749-014-0052-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13749-014-0052-z

Keywords

Navigation