Dipeptidyl Peptidase IV (DPP-IV) Inhibitory Activity of Ultrafiltration and Gel Filtration Fraction of Gelatin Hydrolyaste Derived from Bone of Fish for Antidiabetes

Yoni Atma, Hanifah Nuryani Lioe, Endang Prangdimurti, Hermawan Seftiono, Moh. Taufik, Apon Zaenal Mustopa


Bioactive peptides have been investigated largely for many biofunctional properties. The aim of this research was to determine the inhibitory activity of ultrafiltration (UF) and gel filtration (GF) fractions of gelatin derived from bone of Pangasius catfish against dipeptidyl peptidase IV (DPP-IV). Previous studies have shown that gelatin from skins of salmon, hake, halibut, milkfish, tilapia and bone of pangasius catfish have the activity in DPP-IV inhibition. While, as inhibitor, most of previous and recent studies shown that separation and fractination of gelatin hydrolysate increase their activity. This research was conducted in three stages including gelatin hydrolysates fractination by ultrafiltration (UF), UF fraction loaded into gel filtration (GF) and DPP-IV inhibition measurement. The fish bone gelatin was hydrolyzed using flavourzyme at three enzyme/substrate ratios (E/S of 3%, 6% and 9%) with incubation times 4, 6, and 8 h. Then, the hydrolysates fractioned by ultrafiltration with 3 kDa cutoff membrane continued with Superfine G-25 sephadex column (65 cm x 3 cm, flow rate 1 mL/min). The result shown that both group of fractions i.e UF and GF have inhibitory activity regarding their capacity to inhibit DPP-IV.  The UF fraction >3 kDa derived from 9% (E/S) ratio for hdyrolysis were superb as DPP-IV inhibitor than other fractions, the highest one also has bioactivity higher than other previous fish gelatin fractions. 


dipeptidyl peptidase-IV inhibitor; fish gelatin; antidiabetes type 2; incretin; bioactive peptide.

Full Text:



S. Chakrabarti, S. Guha, and K. Majumder, “Food-Derived Bioactive Peptides in Human Health :,” Nutrients, vol. 10, no. 11, pp. 1–17, 2018.

J. L. Díaz-gómez, F. Castorena-torres, and R. E. Preciado-ortiz, “Anti-Cancer Activity of Maize Bioactive Peptides,” Front Chem., vol. 5, no. June, pp. 1–8, 2017.

M. E. Oseguera-Toledo, E. González de Mejía, R. Reynoso-Camacho, A. Cardador-Martínez, and S. L. Amaya-Llano, “Proteins and bioactive peptides,” Nutrafoods, vol. 13, no. 4, pp. 147–157, 2014.

P. Patil, S. Mandal, S. K. Tomar, and S. Anand, “Food protein-derived bioactive peptides in management of type 2 diabetes,” Eur. J. Nutr., vol. 54, no. 6, pp. 863–880, 2015.

A. B. Nongonierma and R. J. FitzGerald, “Prospects for the management of type 2 diabetes using food protein-derived peptides with dipeptidyl peptidase IV (DPP-IV) inhibitory activity,” Curr. Opin. Food Sci., vol. 8, pp. 19–24, 2016.

K. Kazakos, “Incretin effect: GLP-1, GIP, DPP4,” Diabetes Res. Clin. Pract., vol. 93, pp. S32–S36, 2011.

Y. Zhang, R. Chen, H. Ma, and S. Chen, “Isolation and Identification of Dipeptidyl Peptidase IV-Inhibitory Peptides from Trypsin/Chymotrypsin-Treated Goat Milk Casein Hydrolysates by 2D-TLC and LC-MS/MS,” J. Agric. Food Chem., vol. 63, no. 40, pp. 8819–8828, 2015.

A. B. Olokoba, O. A. Obateru, and L. B. Olokoba, “Type 2 Diabetes Mellitus: A Review of Current Trends,” Oman Med. J., vol. 27, no. 4, pp. 269–273, 2012.

D. A. Tatosian et al., “Dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes treated with saxagliptin, sitagliptin, or vildagliptin,” Diabetes Ther., vol. 4, no. 2, pp. 431–442, 2013.

A. B. Nongonierma, L. Dellafiora, S. Paolella, G. Galaverna, P. Cozzini, and R. J. FitzGerald, “In silico approaches applied to the study of peptide analogs of Ile-Pro-Ile in relation to their dipeptidyl peptidase IV inhibitory properties,” Front. Endocrinol. (Lausanne)., vol. 9, no. JUN, pp. 1–15, 2018.

P. A. Harnedy and R. J. FitzGerald, “Bioactive peptides from marine processing waste and shellfish: A review,” J. Funct. Foods, vol. 4, no. 1, pp. 6–24, 2012.

Y. Atma and H. Ramdhani, “Gelatin extraction from the indigenous Pangasius catfish bone using pineapple liquid waste,” Indones. J. Biotechnol., vol. 22, no. 2, p. 86, 2017.

A. A. Mariod and H. F. Adam, “Review: Gelatin, source, extraction and industrial applications,” Acta Sci. Pol. Technol. Aliment., vol. 12, no. 2, pp. 135–147, 2013.

I. M. E. Lacroix and E. C. Y. Li-Chan, “Comparison of the susceptibility of porcine and human dipeptidyl-peptidase IV to inhibition by protein-derived peptides,” Peptides, vol. 69, pp. 19–25, 2015.

Y. Atma et al., “The proportion–ratio on dipeptidyl aminopeptidase-4 (DP-4) inhibition by gelatin compared to synthetic sitagliptin,” J. Immunoass. Immunochem., vol. 40, no. 4, 2019.

T. Y. Wang, C. H. Hsieh, C. C. Hung, C. L. Jao, M. C. Chen, and K. C. Hsu, “Fish skin gelatin hydrolysates as dipeptidyl peptidase IV inhibitors and glucagon-like peptide-1 stimulators improve glycaemic control in diabetic rats: A comparison between warm- and cold-water fish,” J. Funct. Foods, vol. 19, pp. 330–340, 2015.

R. Jeya Shakila, E. Jeevithan, A. Varatharajakumar, G. Jeyasekaran, and D. Sukumar, “Functional characterization of gelatin extracted from bones of red snapper and grouper in comparison with mammalian gelatin,” LWT - Food Sci. Technol., vol. 48, no. 1, pp. 30–36, 2012.

C. H. Hsieh, T. Y. Wang, C. C. Hung, M. C. Chen, and K. C. Hsu, “Improvement of glycemic control in streptozotocin-induced diabetic rats by Atlantic salmon skin gelatin hydrolysate as the dipeptidyl-peptidase IV inhibitor,” Food Funct., vol. 6, no. 6, pp. 1887–1892, 2015.

E. C. Y. Li-chan, S. Hunag, C. Jao, K. Ho, and K. Hsu, “Peptides Derived from Atlantic Salmon Skin Gelatin as Dipeptidyl-peptidase IV Inhibitors,” J. Agric. Food Chem., vol. 60, no. 4, pp. 973–978, 2012.

M. C. Gomez-Guillen, B. Gimenez, M. E. Lopez-Caballero, and M. P. Montero, “Functional and bioactive properties of collagen and gelatin from alternative sources: A review,” Food Hydrocoll., vol. 25, no. 8, pp. 1813–1827, 2011.

F. Mahmoodani, V. S. Ardekani, S. F. See, S. M. Yusop, and A. S. Babji, “Optimization and physical properties of gelatin extracted from pangasius catfish (Pangasius sutchi) bone,” J. Food Sci. Technol., vol. 51, no. 11, pp. 3104–3113, 2014.

Y. Atma, “Amino acid and proximate composition of fish bone gelatin from different warm-water species: A comparative study,” in IOP Conf Ser: Earth Environ Sci., 2017, vol. 58, no. 012008, pp. 1–5.

Y. Atma et al., “The hydroxyproline content of fish bone gelatin from Indonesian Pangasius catfish by enzymatic hydrolysis for producing the bioactive peptide,” Biofarmasi J. Nat. Prod. Biochem., vol. 16, no. 2, pp. 64–68, 2018.

J. M. Koli, S. Basu, B. B. Nayak, S. B. Patange, A. U. Pagarkar, and V. Gudipati, “Functional characteristics of gelatin extracted from skin and bone of Tiger-toothed croaker (Otolithes ruber) and Pink perch (Nemipterus japonicus),” Food Bioprod. Process., vol. 90, no. 3, pp. 555–562, 2012.

Y. Atma, H. Ramdhani, A. Z. Mustopa, M. Pertiwi, and R. Maisarah, “Karakteristik Fisikokimia Gelatin Tulang Ikan Patin (Pangasius sutchi) Hasil Ekstraksi Menggunakan Limbah Buah Nanas (Ananas comosus),” Agritech, vol. 38, no. 1, p. 56, 2018.

F. Mahmoodani, M. Ghassem, A. S. Babji, S. M. Yusop, and R. Khosrokhavar, “ACE inhibitory activity of pangasius catfish (Pangasius sutchi) skin and bone gelatin hydrolysate,” J. Food Sci. Technol., vol. 51, no. 9, pp. 1847–1856, 2014.

K. Kojima, T. Ham, and T. Kato, “Rapid Chromatographic Purification of Dipeptidyl Peptidase IV in Human Submaxillary Gland,” J. Chromatogr., vol. 189, no. 2, pp. 233–240, 1980.

A. Da Trindade Alfaro, C. Simões Da Costa, G. Graciano Fonseca, and C. Prentice, “Effect of extraction parameters on the properties of gelatin from king weakfish (Macrodon ancylodon) Bones,” Food Sci. Technol. Int., vol. 15, no. 6, pp. 553–562, 2009.

A. Taheri, A. M. Abedian Kenari, A. Gildberg, and S. Behnam, “Extraction and physicochemical characterization of greater lizardfish (Saurida tumbil) skin and bone gelatin,” J. Food Sci., vol. 74, no. 3, pp. 160–165, 2009.

F. Zhang, S. Xu, and Z. Wang, “Pre-treatment optimization and properties of gelatin from freshwater fish scales,” Food Bioprod. Process., vol. 89, no. 3, pp. 185–193, 2011.

H. Y. Liu, J. Han, and S. D. Guo, “Characteristics of the gelatin extracted from Channel Catfish (Ictalurus Punctatus) head bones,” LWT - Food Sci. Technol., vol. 42, no. 2, pp. 540–544, 2009.

S. H. Cho, M. L. Jahncke, K. B. Chin, and J. B. Eun, “The effect of processing conditions on the properties of gelatin from skate (Raja Kenojei) skins,” Food Hydrocoll., vol. 20, no. 6, pp. 810–816, 2006.

J. H. Muyonga, C. G. B. Cole, and K. G. Duodu, “Extraction and physico-chemical characterisation of Nile perch (Lates niloticus) skin and bone gelatin,” Food Hydrocoll., vol. 18, no. 4, pp. 581–592, 2004.

S. L. Huang, C. L. Jao, K. P. Ho, and K. C. Hsu, “Dipeptidyl-peptidase IV inhibitory activity of peptides derived from tuna cooking juice hydrolysates,” Peptides, vol. 35, no. 1, pp. 114–121, 2012.

R. Liu, J. Cheng, and H. Wu, “Discovery of food-derived dipeptidyl peptidase IV inhibitory peptides: A review,” Int. J. Mol. Sci., vol. 20, no. 3, p. E463, 2019.

A. B. Nongonierma and R. J. FitzGerald, “Dipeptidyl peptidase IV inhibitory properties of a whey protein hydrolysate: Influence of fractionation, stability to simulated gastrointestinal digestion and food-drug interaction,” Int. Dairy J., vol. 32, no. 1, pp. 33–39, 2013.

J. Davis et al., “Nature of action of sitagliptin, the dipeptidyl peptidase-IV inhibitor in diabetic animals,” Indian J. Pharmacol., vol. 42, no. 4, p. 229, 2010.

C. Jao, C. Hung, Y. Tung, P. Lin, M. Chen, and K. Hsu, “Review article The development of bioactive peptides from dietary proteins as a dipeptidyl peptidase IV inhibitor for the management of type 2 diabetes,” BioMedicine, vol. 5, no. 3, pp. 9–15, 2015.

S. Huang, C. Hung, C. Jao, Y. Tung, and K. Hsu, “Porcine skin gelatin hydrolysate as a dipeptidyl peptidase IV inhibitor improves glycemic control in streptozotocin-induced diabetic rats,” J. Funct. Foods, vol. 11, no. 91, pp. 235–242, 2014.

K. Hsu, Y. Tung, S. Huang, and C. Jao, “Dipeptidyl Peptidase-IV Inhibitory Activity of Peptides in Porcine Skin Gelatin Hydrolysates,” in Bioactive Food Peptides in Health and Disease, no. 2, B. Hernandez-Ledesma and C. C. Hsieh, Eds. London: Intech, 2013, pp. 205–218.

DOI: http://dx.doi.org/10.18517/ijaseit.9.6.10658


  • There are currently no refbacks.

Published by INSIGHT - Indonesian Society for Knowledge and Human Development