Evidence map›Paper›PMID 39660516›Full record

ArticleProtein and peptide letters2025

Identifying the Role of Individual Seal IAPP Amino Acids in Inhibiting the Aggregation of Human IAPP.

Kate Menefee, Kelsy Larios, Dillon J Rinauro, Angela Tun, Betssy Jauregui, Jessica I Contreras, Luiza A Nogaj, David A Moffet

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Article in Protein and peptide letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Kate MenefeeDepartment of Chemistry and Biochemistry, Loyola Marymount University, 1 LMU Drive, Los Angeles, CA90045, USA.
Kelsy LariosDepartment of Biology, Mount Saint Mary's University, 12001 Chalon Drive, Los Angeles, CA90049, USA.
Dillon J RinauroDepartment of Chemistry and Biochemistry, Loyola Marymount University, 1 LMU Drive, Los Angeles, CA90045, USA.
Angela TunDepartment of Chemistry and Biochemistry, Loyola Marymount University, 1 LMU Drive, Los Angeles, CA90045, USA.
Betssy JaureguiDepartment of Chemistry and Biochemistry, Loyola Marymount University, 1 LMU Drive, Los Angeles, CA90045, USA.
Jessica I ContrerasDepartment of Biology, Mount Saint Mary's University, 12001 Chalon Drive, Los Angeles, CA90049, USA.
Luiza A NogajDepartment of Biology, Mount Saint Mary's University, 12001 Chalon Drive, Los Angeles, CA90049, USA.
David A MoffetDepartment of Chemistry and Biochemistry, Loyola Marymount University, 1 LMU Drive, Los Angeles, CA90045, USA.ORCID 0000-0002-7430-861X

Funding

NIH HHS 2R15DK112172-02
6 · The paper itself

Abstract

introductionThe progression of type 2 diabetes in humans appears to be linked to the loss of insulin-producing β-cells. One of the major contributors to β-cell loss is the formation of toxic human IAPP amyloid (hIAPP, Islet Amyloid Polypeptide, amylin) in the pancreas. Inhibiting the formation of toxic hIAPP amyloid could slow, if not prevent altogether, the progression of type 2 diabetes. Many non-human organisms also express amyloidogenic IAPP variants known to kill pancreatic cells and give rise to diabetes-like symptoms. Surprisingly, some of these non-human IAPP variants function as inhibitors of hIAPP aggregation, raising the possibility of developing non-human IAPP peptides into anti-diabetic therapeutic peptides. One such inhibitory IAPP variant is seal IAPP, which has been shown to inhibit hIAPP aggregation. Seal IAPP only differs from hIAPP by three amino acids. In this study, each of the six seal/human IAPP permutations was analyzed to identify the role of each of the three amino acid positions in inhibiting hIAPP aggregation.

aimsThis study aimed to identify the minimal amino acid substitutions to yield a peptide inhibitor of human IAPP aggregation.

objectiveThe goal of the study was to determine the minimal amino acid substitutions necessary to convert human IAPP into an amyloid-inhibiting peptide.

methodsThe formation of toxic hIAPP amyloid was monitored using Thioflavin T binding assays, atomic force microscopy, and MTT cell rescue studies.

resultsOne seal IAPP variant retained amyloid-inhibition activity, and two variants appeared to be more amyloidogenic and toxic than wild-type human IAPP.

conclusionThese results suggest that inhibition of hIAPP requires both the H18R and F23L substitutions of hIAPP.

Indexed as

Islet Amyloid PolypeptideAmino Acid SequenceAmino Acid SubstitutionAmyloidDiabetes Mellitus, Type 2HumansProtein AggregatesAmyloidIslet Amyloid PolypeptideProtein AggregatesamylinAmyloid inhibitiondiabetesIAPP.islet amyloidprotein aggregation

Identifiers

PMID39660516

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.