Insulinotropic, glucose-lowering, and beta-cell anti-apoptotic actions of peptides related to esculentin-1a(1-21).NH2

V Musale, YHA Abdel-Wahab, Peter Flatt, J. Michael Conlon, Maria Luisa Mangoni

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Long-standing Type 2 diabetes is associated with loss of both β‐cell function and β‐cell mass. Peptides derived from the frogskin host-defense peptide esculentin-1 have been shown to exhibit potent, broad-spectrum antimicrobial activity. The aim of the present study is to determine whether such peptides also show insulinotropic and β-cell protective activities. Esculentin1a(1-21).NH2, esculentin-1b(1-18).NH2, and esculentin-1a(1-14).NH2 produced concentration-dependent stimulations of insulin release from BRIN-BD11 rat clonal β-cells, 1.1B4 human-derived pancreatic β-cells, and isolated mouse islets with no cytotoxicity at concentrations of up to 3 μM. The mechanism of insulinotropic action involved membrane depolarization and an increase in intracellular Ca2+ concentrations. The analogue [D-Lys14, D-Ser17]esculentin-1a(1-21).NH2 (Esc(1-21)-1c) was less potent in vitro than the all L-amino acid containing peptides and esculentin-1a(9-21) was inactive indicating that helicity is an important determinant of insulinotropic activity. However, intraperitoneal injection of Esc(1-21)-1c (75 nmol/ kg body weight) together with a glucose load (18 mmol/kg body weight) in C57BL6 mice improved glucose tolerance with a concomitant increase in insulin secretion, whereas administration of esculentin-1a(1-21).NH2, esculentin-1b(1-18).NH2, and esculentin-1a(1-14) was without signiicant efect on plasma glucose levels. Esc(1-21)-1c (1 µM) protected BRIN-BD11 cells against cytokine-induced apoptosis (P <0.01) and augmented proliferation of the cells (P <0.01) to a similar extent as glucagon-like peptide-1. The data demonstrate that the multifunctional peptide Esc(1-21)-1c, as well as showing therapeutic potential as an anti-infective and wound-healing agent, may constitute a template for development of compounds for treatment of patients with Type 2 diabetes.
LanguageEnglish
Pages723-724
JournalAmino Acids
Volume50
Issue number6
DOIs
Publication statusAccepted/In press - 7 Mar 2018

Fingerprint

Glucose
Peptides
Type 2 Diabetes Mellitus
Body Weight
Insulin
Glucagon-Like Peptide 1
esculentin steroid
Insulin-Secreting Cells
Intraperitoneal Injections
Wound Healing
Cell Proliferation
Apoptosis
Cytokines
Amino Acids
Membranes
Therapeutics

Keywords

  • Esculentin-1a(1-21)
  • Type 2 diabetes
  • Amphibian skin peptide
  • Insulin-release
  • β-cell proliferation
  • Anti-apoptotic peptide

Cite this

@article{7a2bf1d59a664297833211c3db7ce44e,
title = "Insulinotropic, glucose-lowering, and beta-cell anti-apoptotic actions of peptides related to esculentin-1a(1-21).NH2",
abstract = "Long-standing Type 2 diabetes is associated with loss of both β‐cell function and β‐cell mass. Peptides derived from the frogskin host-defense peptide esculentin-1 have been shown to exhibit potent, broad-spectrum antimicrobial activity. The aim of the present study is to determine whether such peptides also show insulinotropic and β-cell protective activities. Esculentin1a(1-21).NH2, esculentin-1b(1-18).NH2, and esculentin-1a(1-14).NH2 produced concentration-dependent stimulations of insulin release from BRIN-BD11 rat clonal β-cells, 1.1B4 human-derived pancreatic β-cells, and isolated mouse islets with no cytotoxicity at concentrations of up to 3 μM. The mechanism of insulinotropic action involved membrane depolarization and an increase in intracellular Ca2+ concentrations. The analogue [D-Lys14, D-Ser17]esculentin-1a(1-21).NH2 (Esc(1-21)-1c) was less potent in vitro than the all L-amino acid containing peptides and esculentin-1a(9-21) was inactive indicating that helicity is an important determinant of insulinotropic activity. However, intraperitoneal injection of Esc(1-21)-1c (75 nmol/ kg body weight) together with a glucose load (18 mmol/kg body weight) in C57BL6 mice improved glucose tolerance with a concomitant increase in insulin secretion, whereas administration of esculentin-1a(1-21).NH2, esculentin-1b(1-18).NH2, and esculentin-1a(1-14) was without signiicant efect on plasma glucose levels. Esc(1-21)-1c (1 µM) protected BRIN-BD11 cells against cytokine-induced apoptosis (P <0.01) and augmented proliferation of the cells (P <0.01) to a similar extent as glucagon-like peptide-1. The data demonstrate that the multifunctional peptide Esc(1-21)-1c, as well as showing therapeutic potential as an anti-infective and wound-healing agent, may constitute a template for development of compounds for treatment of patients with Type 2 diabetes.",
keywords = "Esculentin-1a(1-21), Type 2 diabetes, Amphibian skin peptide, Insulin-release, β-cell proliferation, Anti-apoptotic peptide",
author = "V Musale and YHA Abdel-Wahab and Peter Flatt and Conlon, {J. Michael} and Mangoni, {Maria Luisa}",
year = "2018",
month = "3",
day = "7",
doi = "10.1007/s00726-018-2551-5",
language = "English",
volume = "50",
pages = "723--724",
journal = "Amino Acids",
issn = "0939-4451",
number = "6",

}

Insulinotropic, glucose-lowering, and beta-cell anti-apoptotic actions of peptides related to esculentin-1a(1-21).NH2. / Musale, V; Abdel-Wahab, YHA; Flatt, Peter; Conlon, J. Michael; Mangoni, Maria Luisa.

In: Amino Acids, Vol. 50, No. 6, 07.03.2018, p. 723-724.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Insulinotropic, glucose-lowering, and beta-cell anti-apoptotic actions of peptides related to esculentin-1a(1-21).NH2

AU - Musale, V

AU - Abdel-Wahab, YHA

AU - Flatt, Peter

AU - Conlon, J. Michael

AU - Mangoni, Maria Luisa

PY - 2018/3/7

Y1 - 2018/3/7

N2 - Long-standing Type 2 diabetes is associated with loss of both β‐cell function and β‐cell mass. Peptides derived from the frogskin host-defense peptide esculentin-1 have been shown to exhibit potent, broad-spectrum antimicrobial activity. The aim of the present study is to determine whether such peptides also show insulinotropic and β-cell protective activities. Esculentin1a(1-21).NH2, esculentin-1b(1-18).NH2, and esculentin-1a(1-14).NH2 produced concentration-dependent stimulations of insulin release from BRIN-BD11 rat clonal β-cells, 1.1B4 human-derived pancreatic β-cells, and isolated mouse islets with no cytotoxicity at concentrations of up to 3 μM. The mechanism of insulinotropic action involved membrane depolarization and an increase in intracellular Ca2+ concentrations. The analogue [D-Lys14, D-Ser17]esculentin-1a(1-21).NH2 (Esc(1-21)-1c) was less potent in vitro than the all L-amino acid containing peptides and esculentin-1a(9-21) was inactive indicating that helicity is an important determinant of insulinotropic activity. However, intraperitoneal injection of Esc(1-21)-1c (75 nmol/ kg body weight) together with a glucose load (18 mmol/kg body weight) in C57BL6 mice improved glucose tolerance with a concomitant increase in insulin secretion, whereas administration of esculentin-1a(1-21).NH2, esculentin-1b(1-18).NH2, and esculentin-1a(1-14) was without signiicant efect on plasma glucose levels. Esc(1-21)-1c (1 µM) protected BRIN-BD11 cells against cytokine-induced apoptosis (P <0.01) and augmented proliferation of the cells (P <0.01) to a similar extent as glucagon-like peptide-1. The data demonstrate that the multifunctional peptide Esc(1-21)-1c, as well as showing therapeutic potential as an anti-infective and wound-healing agent, may constitute a template for development of compounds for treatment of patients with Type 2 diabetes.

AB - Long-standing Type 2 diabetes is associated with loss of both β‐cell function and β‐cell mass. Peptides derived from the frogskin host-defense peptide esculentin-1 have been shown to exhibit potent, broad-spectrum antimicrobial activity. The aim of the present study is to determine whether such peptides also show insulinotropic and β-cell protective activities. Esculentin1a(1-21).NH2, esculentin-1b(1-18).NH2, and esculentin-1a(1-14).NH2 produced concentration-dependent stimulations of insulin release from BRIN-BD11 rat clonal β-cells, 1.1B4 human-derived pancreatic β-cells, and isolated mouse islets with no cytotoxicity at concentrations of up to 3 μM. The mechanism of insulinotropic action involved membrane depolarization and an increase in intracellular Ca2+ concentrations. The analogue [D-Lys14, D-Ser17]esculentin-1a(1-21).NH2 (Esc(1-21)-1c) was less potent in vitro than the all L-amino acid containing peptides and esculentin-1a(9-21) was inactive indicating that helicity is an important determinant of insulinotropic activity. However, intraperitoneal injection of Esc(1-21)-1c (75 nmol/ kg body weight) together with a glucose load (18 mmol/kg body weight) in C57BL6 mice improved glucose tolerance with a concomitant increase in insulin secretion, whereas administration of esculentin-1a(1-21).NH2, esculentin-1b(1-18).NH2, and esculentin-1a(1-14) was without signiicant efect on plasma glucose levels. Esc(1-21)-1c (1 µM) protected BRIN-BD11 cells against cytokine-induced apoptosis (P <0.01) and augmented proliferation of the cells (P <0.01) to a similar extent as glucagon-like peptide-1. The data demonstrate that the multifunctional peptide Esc(1-21)-1c, as well as showing therapeutic potential as an anti-infective and wound-healing agent, may constitute a template for development of compounds for treatment of patients with Type 2 diabetes.

KW - Esculentin-1a(1-21)

KW - Type 2 diabetes

KW - Amphibian skin peptide

KW - Insulin-release

KW - β-cell proliferation

KW - Anti-apoptotic peptide

U2 - 10.1007/s00726-018-2551-5

DO - 10.1007/s00726-018-2551-5

M3 - Article

VL - 50

SP - 723

EP - 724

JO - Amino Acids

T2 - Amino Acids

JF - Amino Acids

SN - 0939-4451

IS - 6

ER -