{
  "abstract": "Glucagon (GCG) and glucagon-like peptide 1 (GLP1) are hormones involved in maintaining glucose homeostasis. Diabetic patients display a chronic dysfunction of these hormones along with an increase in copper levels in the bloodstream. Although GCG(1–29) and GLP1(1–37) harbour Cu2+-anchoring groups at their N-terminal regions, their metal-binding properties have not been assesed, nor their implications in metal homeostasis/hormone function. In this study, spectroscopic tools (circular dichroism, electron paramagnetic resonance and X-ray absorption spectroscopy) were used to elucidate the Cu2+-binding properties of GCG and GLP1, and to assay the ability of these hormones to compete for the metal ion with the extracellular Cu2+-binding site of the Copper transporter 1 (CTR1)–the major source of copper uptake in mammalian cells–and Metformin–the Cu2+-binding drug used as first-line treatment for Type 2 diabetes. Our results show that Cu2+-binding to GCG(1–29) and GLP1(1–37) is highly dependent on metal-to-hormone ratio, yielding at least two different Cu2+ complexes (Modes I and II) depending on the metal-to-hormone ratio. Mode I, favoured at low metal-tohormone ratio, can efficiently transfer Cu2+ to the metal-binding site of CTR1, while Mode II can only do a partially transfer, suggesting that Cu2+-hormone speciation could impact metal homeostasis. Metformin can deliver Cu2+ to GCG and GLP1, indicating that this drug could buffer Cu2+ accumulation in the bloodstream in diabetes, without preventing Cu2+-hormone interactions. Altogether, this study elucidates metal-hormone interactions that are crucial to understand the role of Cu2+ in the pathophysiology of diabetes and paves the way for evaluating the potential of Metformin, and other drugs, as regulators of Cu2+-hormone interactions in diabetes.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Yanahi Posadas"
    },
    {
      "name": "Carolina Sánchez-López"
    },
    {
      "name": "Victor E. López-Guerrero"
    },
    {
      "name": "Christophe Den Auwer"
    },
    {
      "name": "José Segovia"
    },
    {
      "name": "Liliana Quintanar",
      "orcid": "0000-0003-3090-7175"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8qadzcfz61mfx.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010094/v1",
  "fulltext_url": null,
  "id": "8qadzcfz61mfx",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010094/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2916|Trace Elements in Health"
    ]
  ],
  "openalex": "W7221015306",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010094/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/8qadzcfz61mfx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.26434/chemrxiv.15010094",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010094/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "source:chemrxiv",
      "subfield": "general"
    }
  ],
  "title": "Copper binding to glucagon and glucagon-like peptide 1: Relevance to diabetes",
  "title_text": "Copper binding to glucagon and glucagon-like peptide 1: Relevance to diabetes",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/8qadzcfz61mfx",
  "venue": "ChemRxiv",
  "versions": []
}