In Vitro and In Vivo Effects of Palmaria palmata Derived Peptides on Glucose Metabolism

Pádraigín A. Harnedy‐Rothwell; Christopher McLaughlin; AV Le Gouic; Ciaran Mullen; Parthsarathy V; Philip J Allsopp; Emeir M. McSorley; RJ Fitzgerald; Finbarr O'Harte

doi:10.1007/s10989-021-10199-8

In Vitro and In Vivo Effects of Palmaria palmata Derived Peptides on Glucose Metabolism

Pádraigín A. Harnedy‐Rothwell, Christopher McLaughlin, AV Le Gouic, Ciaran Mullen, Parthsarathy V, Philip J Allsopp, Emeir M. McSorley, RJ Fitzgerald, Finbarr O'Harte

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Abstract

Three synthetic peptides, ILAP, LLAP and MAGVDHI, derived from a Palmaria palmata protein hydrolysate were assessed for their antidiabetic potential in vitro and in vivo. In addition to inhibiting dipeptidyl peptidase-IV in a cell-based in situ assay all three peptides significantly increased the half-life of the incretin hormone glucagon-like peptide-1 (GLP-1). ILAP and LLAP mediated a significant increase (p < 0.001) in insulin secretion from BRIN-BD11 cells compared to the glucose control, while MAGVDHI had no insulinotropic activity at an eqimolar concentration (10 ^–6 M). A significant increase in the concentration of cyclic adenosine monophosphate production in BRIN-BD11 cells mediated by ILAP (p < 0.001) and LLAP (p < 0.01) compared to the basal control, would indicate that insulin secretion may be mediated by membrane based activation. Furthermore, ILAP and LLAP acted as glucose-dependent insulinotropic polypeptide (GIP) secretagogues, stimulating a significant increase (p < 0.01) in the concentration of GIP released from enteroendocrine STC-1 cells compared to the glucose control. When tested in vivo in healthy male NIH Swiss mice, ILAP and LLAP, mediated a significant increase (p < 0.01) in plasma insulin and decrease (p < 0.05) in blood glucose, respectively, compared to the control. MAGVDHI mediated a significant (p < 0.001) sustained reduction in food intake in food deprived trained mice. These results demonstrate that the Palmaria palmata peptides studied herein have prospective antidiabetic activity and have the potential to act as agents that can be used alone or in combination with drugs, to aid in the prevention and management of Type 2 diabetes mellitus.

Original language	English
Pages (from-to)	1667–1676
Number of pages	10
Journal	International Journal of Peptide Research and Therapeutics
Volume	27
Issue number	3
DOIs	https://doi.org/10.1007/s10989-021-10199-8
Publication status	Published (in print/issue) - Sept 2021

Bibliographical note

Funding Information:
This research was funded under the National Development Plan, through the Food Institutional Research Measure, administered by the Department of Agriculture, Food and the Marine, Ireland under Grant Numbers 13/F/467 and 14/F/873 and a Northern Ireland Department of Employment and Learning PhD scholarship for Chris M. McLaughlin.

Funding Information:
The authors would like to acknowledge the Department of Agriculture, Food and the Marine, Ireland (under Grant Numbers 13/F/467 and 14/F/873) and the Northern Ireland Department of Employment and Learning for financial support and Dr. Thanyaporn Kleekayai, University of Limerick, for growth of the Caco-2 cells used in the in situ DPP-IV inhibitory activity quantification study herein.

Publisher Copyright:
© 2021, The Author(s).

Keywords

Bioactive peptides
dipeptidyl peptidase-IV inhibition
Glucagon-like peptide-1 (GLP-1)
Dipeptidyl peptidase-IV (DPP-IV) inhibition · GGlucosedependent insulinotropic polypeptide (GIP)
Type 2 diabetes
Palmaria palmata

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10989-021-10199-8

Harnedy-Rothwell_et_al-2021Author Accepted Manuscript, 1.15 MB

Cite this

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title = "In Vitro and In Vivo Effects of Palmaria palmata Derived Peptides on Glucose Metabolism",

abstract = "Three synthetic peptides, ILAP, LLAP and MAGVDHI, derived from a Palmaria palmata protein hydrolysate were assessed for their antidiabetic potential in vitro and in vivo. In addition to inhibiting dipeptidyl peptidase-IV in a cell-based in situ assay all three peptides significantly increased the half-life of the incretin hormone glucagon-like peptide-1 (GLP-1). ILAP and LLAP mediated a significant increase (p < 0.001) in insulin secretion from BRIN-BD11 cells compared to the glucose control, while MAGVDHI had no insulinotropic activity at an eqimolar concentration (10 –6 M). A significant increase in the concentration of cyclic adenosine monophosphate production in BRIN-BD11 cells mediated by ILAP (p < 0.001) and LLAP (p < 0.01) compared to the basal control, would indicate that insulin secretion may be mediated by membrane based activation. Furthermore, ILAP and LLAP acted as glucose-dependent insulinotropic polypeptide (GIP) secretagogues, stimulating a significant increase (p < 0.01) in the concentration of GIP released from enteroendocrine STC-1 cells compared to the glucose control. When tested in vivo in healthy male NIH Swiss mice, ILAP and LLAP, mediated a significant increase (p < 0.01) in plasma insulin and decrease (p < 0.05) in blood glucose, respectively, compared to the control. MAGVDHI mediated a significant (p < 0.001) sustained reduction in food intake in food deprived trained mice. These results demonstrate that the Palmaria palmata peptides studied herein have prospective antidiabetic activity and have the potential to act as agents that can be used alone or in combination with drugs, to aid in the prevention and management of Type 2 diabetes mellitus. ",

keywords = "Bioactive peptides, dipeptidyl peptidase-IV inhibition, Glucagon-like peptide-1 (GLP-1), Dipeptidyl peptidase-IV (DPP-IV) inhibition · GGlucosedependent insulinotropic polypeptide (GIP), Type 2 diabetes, Palmaria palmata",

author = "Harnedy‐Rothwell, {P{\'a}draig{\'i}n A.} and Christopher McLaughlin and {Le Gouic}, AV and Ciaran Mullen and Parthsarathy V and Allsopp, {Philip J} and McSorley, {Emeir M.} and RJ Fitzgerald and Finbarr O'Harte",

note = "Funding Information: This research was funded under the National Development Plan, through the Food Institutional Research Measure, administered by the Department of Agriculture, Food and the Marine, Ireland under Grant Numbers 13/F/467 and 14/F/873 and a Northern Ireland Department of Employment and Learning PhD scholarship for Chris M. McLaughlin. Funding Information: The authors would like to acknowledge the Department of Agriculture, Food and the Marine, Ireland (under Grant Numbers 13/F/467 and 14/F/873) and the Northern Ireland Department of Employment and Learning for financial support and Dr. Thanyaporn Kleekayai, University of Limerick, for growth of the Caco-2 cells used in the in situ DPP-IV inhibitory activity quantification study herein. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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T1 - In Vitro and In Vivo Effects of Palmaria palmata Derived Peptides on Glucose Metabolism

AU - Harnedy‐Rothwell, Pádraigín A.

AU - McLaughlin, Christopher

AU - Le Gouic, AV

AU - Mullen, Ciaran

AU - V, Parthsarathy

AU - Allsopp, Philip J

AU - McSorley, Emeir M.

AU - Fitzgerald, RJ

AU - O'Harte, Finbarr

N1 - Funding Information: This research was funded under the National Development Plan, through the Food Institutional Research Measure, administered by the Department of Agriculture, Food and the Marine, Ireland under Grant Numbers 13/F/467 and 14/F/873 and a Northern Ireland Department of Employment and Learning PhD scholarship for Chris M. McLaughlin. Funding Information: The authors would like to acknowledge the Department of Agriculture, Food and the Marine, Ireland (under Grant Numbers 13/F/467 and 14/F/873) and the Northern Ireland Department of Employment and Learning for financial support and Dr. Thanyaporn Kleekayai, University of Limerick, for growth of the Caco-2 cells used in the in situ DPP-IV inhibitory activity quantification study herein. Publisher Copyright: © 2021, The Author(s).

PY - 2021/9

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N2 - Three synthetic peptides, ILAP, LLAP and MAGVDHI, derived from a Palmaria palmata protein hydrolysate were assessed for their antidiabetic potential in vitro and in vivo. In addition to inhibiting dipeptidyl peptidase-IV in a cell-based in situ assay all three peptides significantly increased the half-life of the incretin hormone glucagon-like peptide-1 (GLP-1). ILAP and LLAP mediated a significant increase (p < 0.001) in insulin secretion from BRIN-BD11 cells compared to the glucose control, while MAGVDHI had no insulinotropic activity at an eqimolar concentration (10 –6 M). A significant increase in the concentration of cyclic adenosine monophosphate production in BRIN-BD11 cells mediated by ILAP (p < 0.001) and LLAP (p < 0.01) compared to the basal control, would indicate that insulin secretion may be mediated by membrane based activation. Furthermore, ILAP and LLAP acted as glucose-dependent insulinotropic polypeptide (GIP) secretagogues, stimulating a significant increase (p < 0.01) in the concentration of GIP released from enteroendocrine STC-1 cells compared to the glucose control. When tested in vivo in healthy male NIH Swiss mice, ILAP and LLAP, mediated a significant increase (p < 0.01) in plasma insulin and decrease (p < 0.05) in blood glucose, respectively, compared to the control. MAGVDHI mediated a significant (p < 0.001) sustained reduction in food intake in food deprived trained mice. These results demonstrate that the Palmaria palmata peptides studied herein have prospective antidiabetic activity and have the potential to act as agents that can be used alone or in combination with drugs, to aid in the prevention and management of Type 2 diabetes mellitus.

AB - Three synthetic peptides, ILAP, LLAP and MAGVDHI, derived from a Palmaria palmata protein hydrolysate were assessed for their antidiabetic potential in vitro and in vivo. In addition to inhibiting dipeptidyl peptidase-IV in a cell-based in situ assay all three peptides significantly increased the half-life of the incretin hormone glucagon-like peptide-1 (GLP-1). ILAP and LLAP mediated a significant increase (p < 0.001) in insulin secretion from BRIN-BD11 cells compared to the glucose control, while MAGVDHI had no insulinotropic activity at an eqimolar concentration (10 –6 M). A significant increase in the concentration of cyclic adenosine monophosphate production in BRIN-BD11 cells mediated by ILAP (p < 0.001) and LLAP (p < 0.01) compared to the basal control, would indicate that insulin secretion may be mediated by membrane based activation. Furthermore, ILAP and LLAP acted as glucose-dependent insulinotropic polypeptide (GIP) secretagogues, stimulating a significant increase (p < 0.01) in the concentration of GIP released from enteroendocrine STC-1 cells compared to the glucose control. When tested in vivo in healthy male NIH Swiss mice, ILAP and LLAP, mediated a significant increase (p < 0.01) in plasma insulin and decrease (p < 0.05) in blood glucose, respectively, compared to the control. MAGVDHI mediated a significant (p < 0.001) sustained reduction in food intake in food deprived trained mice. These results demonstrate that the Palmaria palmata peptides studied herein have prospective antidiabetic activity and have the potential to act as agents that can be used alone or in combination with drugs, to aid in the prevention and management of Type 2 diabetes mellitus.

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KW - Glucagon-like peptide-1 (GLP-1)

KW - Dipeptidyl peptidase-IV (DPP-IV) inhibition · GGlucosedependent insulinotropic polypeptide (GIP)

KW - Type 2 diabetes

KW - Palmaria palmata

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DO - 10.1007/s10989-021-10199-8

M3 - Article

SN - 1573-3149

VL - 27

SP - 1667

EP - 1676

JO - International Journal of Peptide Research and Therapeutics

JF - International Journal of Peptide Research and Therapeutics

IS - 3

ER -

In Vitro and In Vivo Effects of Palmaria palmata Derived Peptides on Glucose Metabolism

Abstract

Bibliographical note

Keywords

UN SDGs

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