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.
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.
McInerney
M F
MF
Department of Medicinal & Biological Chemistry, College of Pharmacy, University of Toledo, OH 43606, USA.
Seidel
M J
MJ
Nguyen
J M
JM
Flynn
J C
JC
Sturm
N
N
Lee
H
H
Zhang
Z
Z
Tillekeratne
L M
LM
Hudson
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000737:chemistry* / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*
D007328:Insulin; D007329:Insulin Antagonists; D007375:Interleukin-1; D010446:Peptide Fragments; D005947:Glucose