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    Effects of a 33 residue interleukin-1 beta peptide and the antioxidant PQQ on interleukin-1 beta-mediated inhibition of glucose-stimulated insulin release from cultured mouse pancreatic islets.

    Abstract

    Interleukin-1 beta (IL-1 beta) significantly inhibits insulin secretion from glucose stimulated islet cells. The mechanism for this inhibition has been hypothesized to be due to stimulation of the inducible form of nitric oxide synthase and a resulting increase in nitric oxide (NO) concentration. Ways to block the effect of IL-1 beta have focused on blocking the binding of IL-1 beta to the IL-1 receptor and the use of antioxidants to neutralize increases in NO. This report focuses on a 33 residue peptide synthesized based on the C-terminal region of the IL-1 beta molecule, a reported binding site of the IL-1 beta molecule, and the redoxcycling antioxidant pyrroloquinoline quinone (PQQ). The 33 residue peptide did not function as an antagonist, but as a weak agonist. High concentrations of PQQ itself inhibited glucose-dependent insulin release while low concentrations did not. PQQ had no effect on the actions of IL-1 beta. Three isosteric and isomeric analogues of PQQ were also investigated. One of the PQQ isomers had an inhibitory effect on insulin secretion at low concentrations where PQQ had no effect. These results reflect the sensitivity of islets to oxidative stress.

    Authors+Show Affiliations

    McInerney MF
    ,

    Department of Medicinal & Biological Chemistry, College of Pharmacy, University of Toledo, OH 43606, USA.

    Seidel MJ
    ,
    Nguyen JM
    ,
    Flynn JC
    ,
    Sturm N
    ,
    Lee H
    ,
    Zhang Z
    ,
    Tillekeratne LM
    ,
    Hudson RA

    Source

    MeSH

    Amino Acid Sequence
    Animals
    Cells, Cultured
    Glucose
    Insulin
    Insulin Antagonists
    Insulin Secretion
    Interleukin-1
    Islets of Langerhans
    Mice
    Mice, Inbred CBA
    Mice, Inbred NOD
    Molecular Sequence Data
    Peptide Fragments

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    8987109

    Citation

    TY - JOUR T1 - Effects of a 33 residue interleukin-1 beta peptide and the antioxidant PQQ on interleukin-1 beta-mediated inhibition of glucose-stimulated insulin release from cultured mouse pancreatic islets. AU - McInerney,M F, AU - Seidel,M J, AU - Nguyen,J M, AU - Flynn,J C, AU - Sturm,N, AU - Lee,H, AU - Zhang,Z, AU - Tillekeratne,L M, AU - Hudson,R A, PY - 1996/11/1/pubmed PY - 1996/11/1/medline PY - 1996/11/1/entrez SP - 115 EP - 28 JF - Research communications in molecular pathology and pharmacology JO - Res. Commun. Mol. Pathol. Pharmacol. VL - 94 IS - 2 N2 - Interleukin-1 beta (IL-1 beta) significantly inhibits insulin secretion from glucose stimulated islet cells. The mechanism for this inhibition has been hypothesized to be due to stimulation of the inducible form of nitric oxide synthase and a resulting increase in nitric oxide (NO) concentration. Ways to block the effect of IL-1 beta have focused on blocking the binding of IL-1 beta to the IL-1 receptor and the use of antioxidants to neutralize increases in NO. This report focuses on a 33 residue peptide synthesized based on the C-terminal region of the IL-1 beta molecule, a reported binding site of the IL-1 beta molecule, and the redoxcycling antioxidant pyrroloquinoline quinone (PQQ). The 33 residue peptide did not function as an antagonist, but as a weak agonist. High concentrations of PQQ itself inhibited glucose-dependent insulin release while low concentrations did not. PQQ had no effect on the actions of IL-1 beta. Three isosteric and isomeric analogues of PQQ were also investigated. One of the PQQ isomers had an inhibitory effect on insulin secretion at low concentrations where PQQ had no effect. These results reflect the sensitivity of islets to oxidative stress. SN - 1078-0297 UR - https://www.unboundmedicine.com/medline/citation/8987109/Effects_of_a_33_residue_interleukin_1_beta_peptide_and_the_antioxidant_PQQ_on_interleukin_1_beta_mediated_inhibition_of_glucose_stimulated_insulin_release_from_cultured_mouse_pancreatic_islets_ L2 - https://medlineplus.gov/diabetesmedicines.html ER -