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Multiple antidiabetic effects of three α-glucosidase inhibitory peptides, PFP, YPL and YPG: Dipeptidyl peptidase–IV inhibition, suppression of lipid accumulation in differentiated 3T3-L1 adipocytes and scavenging activity on methylglyoxal
Antidiabetic agents with multiple targets have the greatest pharmaceutical potential. In this study, three α-glucosidase inhibitory peptides, PFP, YPL and YPG, were investigated for additional antidiabetic targets viz.; dipeptidyl peptidase-IV inhibition (DPP-IV), lipid accumulation and the differen...
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| Published in: | International journal of biological macromolecules 2019-02, Vol.122, p.104-114 |
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| container_title | International journal of biological macromolecules |
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| creator | Ibrahim, Mohammed Auwal Serem, June C. Bester, Megan J. Neitz, Albert W. Gaspar, Anabella R.M. |
| description | Antidiabetic agents with multiple targets have the greatest pharmaceutical potential. In this study, three α-glucosidase inhibitory peptides, PFP, YPL and YPG, were investigated for additional antidiabetic targets viz.; dipeptidyl peptidase-IV inhibition (DPP-IV), lipid accumulation and the differentiation of 3T3-L1 adipocytes, and scavenging of methylglyoxal (MGO), reactive oxygen species (ROS) and nitric oxide (NO). The peptides were subjected to molecular docking on human DPP-IV where the binding free energies were PFP |
| doi_str_mv | 10.1016/j.ijbiomac.2018.10.152 |
| format | article |
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•The peptides PFP, YPL and YPG were investigated for multiple antidiabetic effects.•In vitro, the peptides inhibited dipeptidyl peptidase-4 but YPG was the best.•YPG was the best in preventing lipid accumulation in 3T3-L1 differentiated adipocytes.•Along with other parameters, YPG is the best multifunctional antidiabetic candidate.</description><identifier>ISSN: 0141-8130</identifier><identifier>EISSN: 1879-0003</identifier><identifier>DOI: 10.1016/j.ijbiomac.2018.10.152</identifier><identifier>PMID: 30365987</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>3T3-L1 Cells ; Adipocyte differentiation ; Adipocytes - cytology ; Adipocytes - drug effects ; alpha-Glucosidases - metabolism ; Amino Acid Sequence ; Animals ; Antioxidant activity ; Cell Differentiation - drug effects ; Dipeptidyl peptidase IV inhibition ; Dipeptidyl-Peptidase IV Inhibitors - chemistry ; Dipeptidyl-Peptidase IV Inhibitors - metabolism ; Dipeptidyl-Peptidase IV Inhibitors - pharmacology ; Free Radical Scavengers - chemistry ; Free Radical Scavengers - metabolism ; Free Radical Scavengers - pharmacology ; Glycoside Hydrolase Inhibitors - chemistry ; Glycoside Hydrolase Inhibitors - metabolism ; Glycoside Hydrolase Inhibitors - pharmacology ; Humans ; Hypoglycemic Agents - chemistry ; Hypoglycemic Agents - pharmacology ; Lipid Metabolism - drug effects ; Methylglyoxal ; Mice ; Molecular docking ; Molecular Docking Simulation ; Oligopeptides - chemistry ; Oligopeptides - metabolism ; Oligopeptides - pharmacology ; Pyruvaldehyde - metabolism ; α-Glucosidase inhibitory peptides</subject><ispartof>International journal of biological macromolecules, 2019-02, Vol.122, p.104-114</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-568e90c0f3889e269030098a8ff950c63779c30983af433a9ca3f511ad0311a63</citedby><cites>FETCH-LOGICAL-c416t-568e90c0f3889e269030098a8ff950c63779c30983af433a9ca3f511ad0311a63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30365987$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ibrahim, Mohammed Auwal</creatorcontrib><creatorcontrib>Serem, June C.</creatorcontrib><creatorcontrib>Bester, Megan J.</creatorcontrib><creatorcontrib>Neitz, Albert W.</creatorcontrib><creatorcontrib>Gaspar, Anabella R.M.</creatorcontrib><title>Multiple antidiabetic effects of three α-glucosidase inhibitory peptides, PFP, YPL and YPG: Dipeptidyl peptidase–IV inhibition, suppression of lipid accumulation in differentiated 3T3-L1 adipocytes and scavenging activity on methylglyoxal</title><title>International journal of biological macromolecules</title><addtitle>Int J Biol Macromol</addtitle><description>Antidiabetic agents with multiple targets have the greatest pharmaceutical potential. In this study, three α-glucosidase inhibitory peptides, PFP, YPL and YPG, were investigated for additional antidiabetic targets viz.; dipeptidyl peptidase-IV inhibition (DPP-IV), lipid accumulation and the differentiation of 3T3-L1 adipocytes, and scavenging of methylglyoxal (MGO), reactive oxygen species (ROS) and nitric oxide (NO). The peptides were subjected to molecular docking on human DPP-IV where the binding free energies were PFP < YPG < YPL < diprotin A while hydrogen bond interactions were critical in the binding of YPL and YPG. Moreover, YPG demonstrated significantly higher (p < 0.05) in vitro DPP-IV inhibition than PFP and YPL. Kinetic analysis revealed that all three peptides are uncompetitive inhibitors of DPP-IV while YPG had the lowest inhibition binding constant. PFP and YPG prevented lipid accumulation in 3T3-L1 differentiated adipocytes but may be due to cytotoxicity for PFP. The peptides scavenged MGO, ROS and NO but only the ROS and NO scavenging activities of YPG were comparable to glutathione. In conclusion, PFP, YPL and YPG exhibited DPP-IV inhibitory activity, reduced adipocyte differentiation and lipid accumulation as well as scavenged MGO, ROS and NO. However, YPG had the best potential as a possible multifunctional antidiabetic agent.
•The peptides PFP, YPL and YPG were investigated for multiple antidiabetic effects.•In vitro, the peptides inhibited dipeptidyl peptidase-4 but YPG was the best.•YPG was the best in preventing lipid accumulation in 3T3-L1 differentiated adipocytes.•Along with other parameters, YPG is the best multifunctional antidiabetic candidate.</description><subject>3T3-L1 Cells</subject><subject>Adipocyte differentiation</subject><subject>Adipocytes - cytology</subject><subject>Adipocytes - drug effects</subject><subject>alpha-Glucosidases - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antioxidant activity</subject><subject>Cell Differentiation - drug effects</subject><subject>Dipeptidyl peptidase IV inhibition</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - chemistry</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - metabolism</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - pharmacology</subject><subject>Free Radical Scavengers - chemistry</subject><subject>Free Radical Scavengers - metabolism</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Glycoside Hydrolase Inhibitors - chemistry</subject><subject>Glycoside Hydrolase Inhibitors - metabolism</subject><subject>Glycoside Hydrolase Inhibitors - pharmacology</subject><subject>Humans</subject><subject>Hypoglycemic Agents - chemistry</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Lipid Metabolism - drug effects</subject><subject>Methylglyoxal</subject><subject>Mice</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Oligopeptides - chemistry</subject><subject>Oligopeptides - metabolism</subject><subject>Oligopeptides - pharmacology</subject><subject>Pyruvaldehyde - metabolism</subject><subject>α-Glucosidase inhibitory peptides</subject><issn>0141-8130</issn><issn>1879-0003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFUU2O0zAUthCIKQNXGHnJoil23KQJK9AMM4xURBcDEqvItV_aVzlxsJ2K7LgDJ-EiHIIbcAOc_rBl4yd__n6e9RFyxdmMM56_2s1wt0bbSDVLGS9mI56lj8iEF4syYYyJx2TC-JwnBRfsgjzzfhfRPOPFU3IhmMizslhMyJ8PvQnYGaCyDahRriGgolDXoIKntqZh6wDor5_JxvTKetTSA8V2i2sM1g20gy4KwU_p6nY1pV9Wy2il47x7TW_w-DqYEy1qf3__cf_5bIC2nVLfd50D7-NlDDTYoaZSqb7pjRwpkU01xpUcxCVlAE3Fg0iWnEqNnVVDAH8I9Uruod1gu4n6gHsMA43yBsJ2MBsz2G_SPCdPamk8vDjNS_Lp9t3D9ftk-fHu_vrtMlFznockywsomWK1KIoS0rxkgrGykEVdlxlTuVgsSiUiImQ9F0KWSoo641xqJuKZi0vy8ujbOfu1Bx-qBr0CY2QLtvdVyg-msZBIzY9U5az3Duqqc9hIN1ScVWPd1a46112NdR_wLI3Cq1NGv25A_5Od-42EN0cCxJ_uEVzlFUKrQKOLBVfa4v8y_gJxPsWn</recordid><startdate>20190201</startdate><enddate>20190201</enddate><creator>Ibrahim, Mohammed Auwal</creator><creator>Serem, June C.</creator><creator>Bester, Megan J.</creator><creator>Neitz, Albert W.</creator><creator>Gaspar, Anabella R.M.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20190201</creationdate><title>Multiple antidiabetic effects of three α-glucosidase inhibitory peptides, PFP, YPL and YPG: Dipeptidyl peptidase–IV inhibition, suppression of lipid accumulation in differentiated 3T3-L1 adipocytes and scavenging activity on methylglyoxal</title><author>Ibrahim, Mohammed Auwal ; Serem, June C. ; Bester, Megan J. ; Neitz, Albert W. ; Gaspar, Anabella R.M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-568e90c0f3889e269030098a8ff950c63779c30983af433a9ca3f511ad0311a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>3T3-L1 Cells</topic><topic>Adipocyte differentiation</topic><topic>Adipocytes - cytology</topic><topic>Adipocytes - drug effects</topic><topic>alpha-Glucosidases - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antioxidant activity</topic><topic>Cell Differentiation - drug effects</topic><topic>Dipeptidyl peptidase IV inhibition</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - chemistry</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - metabolism</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - pharmacology</topic><topic>Free Radical Scavengers - chemistry</topic><topic>Free Radical Scavengers - metabolism</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>Glycoside Hydrolase Inhibitors - chemistry</topic><topic>Glycoside Hydrolase Inhibitors - metabolism</topic><topic>Glycoside Hydrolase Inhibitors - pharmacology</topic><topic>Humans</topic><topic>Hypoglycemic Agents - chemistry</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Lipid Metabolism - drug effects</topic><topic>Methylglyoxal</topic><topic>Mice</topic><topic>Molecular docking</topic><topic>Molecular Docking Simulation</topic><topic>Oligopeptides - chemistry</topic><topic>Oligopeptides - metabolism</topic><topic>Oligopeptides - pharmacology</topic><topic>Pyruvaldehyde - metabolism</topic><topic>α-Glucosidase inhibitory peptides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ibrahim, Mohammed Auwal</creatorcontrib><creatorcontrib>Serem, June C.</creatorcontrib><creatorcontrib>Bester, Megan J.</creatorcontrib><creatorcontrib>Neitz, Albert W.</creatorcontrib><creatorcontrib>Gaspar, Anabella R.M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of biological macromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ibrahim, Mohammed Auwal</au><au>Serem, June C.</au><au>Bester, Megan J.</au><au>Neitz, Albert W.</au><au>Gaspar, Anabella R.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiple antidiabetic effects of three α-glucosidase inhibitory peptides, PFP, YPL and YPG: Dipeptidyl peptidase–IV inhibition, suppression of lipid accumulation in differentiated 3T3-L1 adipocytes and scavenging activity on methylglyoxal</atitle><jtitle>International journal of biological macromolecules</jtitle><addtitle>Int J Biol Macromol</addtitle><date>2019-02-01</date><risdate>2019</risdate><volume>122</volume><spage>104</spage><epage>114</epage><pages>104-114</pages><issn>0141-8130</issn><eissn>1879-0003</eissn><abstract>Antidiabetic agents with multiple targets have the greatest pharmaceutical potential. In this study, three α-glucosidase inhibitory peptides, PFP, YPL and YPG, were investigated for additional antidiabetic targets viz.; dipeptidyl peptidase-IV inhibition (DPP-IV), lipid accumulation and the differentiation of 3T3-L1 adipocytes, and scavenging of methylglyoxal (MGO), reactive oxygen species (ROS) and nitric oxide (NO). The peptides were subjected to molecular docking on human DPP-IV where the binding free energies were PFP < YPG < YPL < diprotin A while hydrogen bond interactions were critical in the binding of YPL and YPG. Moreover, YPG demonstrated significantly higher (p < 0.05) in vitro DPP-IV inhibition than PFP and YPL. Kinetic analysis revealed that all three peptides are uncompetitive inhibitors of DPP-IV while YPG had the lowest inhibition binding constant. PFP and YPG prevented lipid accumulation in 3T3-L1 differentiated adipocytes but may be due to cytotoxicity for PFP. The peptides scavenged MGO, ROS and NO but only the ROS and NO scavenging activities of YPG were comparable to glutathione. In conclusion, PFP, YPL and YPG exhibited DPP-IV inhibitory activity, reduced adipocyte differentiation and lipid accumulation as well as scavenged MGO, ROS and NO. However, YPG had the best potential as a possible multifunctional antidiabetic agent.
•The peptides PFP, YPL and YPG were investigated for multiple antidiabetic effects.•In vitro, the peptides inhibited dipeptidyl peptidase-4 but YPG was the best.•YPG was the best in preventing lipid accumulation in 3T3-L1 differentiated adipocytes.•Along with other parameters, YPG is the best multifunctional antidiabetic candidate.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30365987</pmid><doi>10.1016/j.ijbiomac.2018.10.152</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3T3-L1 Cells Adipocyte differentiation Adipocytes - cytology Adipocytes - drug effects alpha-Glucosidases - metabolism Amino Acid Sequence Animals Antioxidant activity Cell Differentiation - drug effects Dipeptidyl peptidase IV inhibition Dipeptidyl-Peptidase IV Inhibitors - chemistry Dipeptidyl-Peptidase IV Inhibitors - metabolism Dipeptidyl-Peptidase IV Inhibitors - pharmacology Free Radical Scavengers - chemistry Free Radical Scavengers - metabolism Free Radical Scavengers - pharmacology Glycoside Hydrolase Inhibitors - chemistry Glycoside Hydrolase Inhibitors - metabolism Glycoside Hydrolase Inhibitors - pharmacology Humans Hypoglycemic Agents - chemistry Hypoglycemic Agents - pharmacology Lipid Metabolism - drug effects Methylglyoxal Mice Molecular docking Molecular Docking Simulation Oligopeptides - chemistry Oligopeptides - metabolism Oligopeptides - pharmacology Pyruvaldehyde - metabolism α-Glucosidase inhibitory peptides |
| title | Multiple antidiabetic effects of three α-glucosidase inhibitory peptides, PFP, YPL and YPG: Dipeptidyl peptidase–IV inhibition, suppression of lipid accumulation in differentiated 3T3-L1 adipocytes and scavenging activity on methylglyoxal |
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