A novel peptide isolated from Aphonopelma chalcodes tarantula venom with benefits on pancreatic islet function and appetite control

A Coulter-Parkhill, Swm Dobbin, N Tanday, V A Gault, S McClean, N Irwin

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2 Citations (Scopus)
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Abstract

Proof-of-concept for therapeutic application of venom-derived compounds in diabetes is exemplified by the incretin mimetic, exenatide, originally extracted from the saliva of the venomous Heloderma suspectum lizard. In this regard, we have isolated and sequenced a novel 28 amino acid peptide named Δ-theraphotoxin-Ac1 (Δ-TRTX-AC1) from venom of the Mexican Blond tarantula spider Aphonopelma chalcodes, with potential therapeutic benefits for diabetes. Following confirmation of the structure and safety profile of the synthetic peptide, assessment of enzymatic stability and effects of Δ-TRTX-AC1 on in vitro beta-cell function were studied, alongside potential mechanisms. Glucose homeostatic and satiety actions of Δ-TRTX-AC1 alone, and in combination with exenatide, were then assessed in C57BL/6 mice. Synthetic Δ-TRTX-AC1 was shown to adopt a characteristic inhibitor cysteine knot (ICK)-like structure and was non-toxic to beta-cells. Δ-TRTX-AC1 evoked glucose-dependent insulin secretion from BRIN BD11 cells with bioactivity confirmed in murine islets. Insulin secretory potency was established to be dependent on KATP and Ca2+ channel beta-cell signalling. In addition, Δ-TRTX-AC1 enhanced beta-cell proliferation and provided significant protection against cytokine-induced apoptosis. When injected co-jointly with glucose in mice at a dose of 250 nmol/kg, Δ-TRTX-AC1 decreased blood-glucose levels and evoked a significant satiating effect. Moreover, whilst Δ-TRTX-AC1 did not enhance exenatide induced benefits on glucose homeostasis, the peptide significantly augmented exenatide mediated suppression of appetite. Together these data highlight the therapeutic potential of tarantula spider venom-derived peptides, such as Δ-TRTX-Ac1, for diabetes and related obesity.

Original languageEnglish
Article number115544
Pages (from-to)1-9
Number of pages10
JournalBiochemical Pharmacology
Volume212
Early online date11 Apr 2023
DOIs
Publication statusPublished (in print/issue) - 30 Jun 2023

Bibliographical note

Funding Information:
These studies were supported by a Diabetes UK funded PhD studentship (ACP), a Nicobrand Ltd., Coleraine funded PhD studentship (SWMD) and Ulster University Research Funding support.

Publisher Copyright:
© 2023 The Author(s)

Keywords

  • Aphonopelma chalcodes
  • Venom-derived peptides
  • Beta-cell function
  • Satiety

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