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

6 Citations (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.
Original languageEnglish
Pages (from-to)723-724
JournalAmino Acids
Volume50
Issue number6
DOIs
Publication statusAccepted/In press - 7 Mar 2018

Keywords

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

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