Adiponectin receptor fragmentation in mouse models of type 1 and type 2 diabetes

dc.contributor.authorFrabutt, Dylan
dc.contributor.authorStull, Natalie
dc.contributor.authorPineros, Annie R.
dc.contributor.authorTersey, Sarah A.
dc.contributor.authorScheuner, Donalyn
dc.contributor.authorMastracci, Teresa L.
dc.contributor.authorPugia, Michael J.
dc.contributor.departmentBiology, School of Scienceen_US
dc.date.accessioned2023-02-23T10:46:49Z
dc.date.available2023-02-23T10:46:49Z
dc.date.issued2020
dc.description.abstractThe protein hormone adiponectin regulates glucose and fatty acid metabolism by binding to two PAQR-family receptors (AdipoR1 and AdipoR2). Both receptors feature a C-terminal segment which is released by proteolysis to form a freely circulating C-terminal fragment (CTF) found in the plasma of normal individuals but not in some undefined diabetes patients. The AdipoR1-CTF344-376 is a competitive inhibitor of tumor necrosis factor α cleavage enzyme (TACE) but it contains a shorter peptide domain (AdipoR1 CTF351-362) that is a strong non-competitive inhibitor of insulin-degrading enzyme (IDE). The link between adiponectin receptor fragmentation and diabetes pathology is unclear but could lead to new therapeutic strategies. We therefore investigated physiological variations in the concentrations of CTF in non-obese diabetic (NOD/ShiLtJ) mice and C57BL/6 mice with diet-induced obesity (DIO) as models of diabetes types 1 and 2, respectively. We tested for changes in adiponectin receptor signaling, immune responses, disease progression, and the abundance of neutralizing autoantibodies. Finally, we administered exogenous AdipoR1-CTF peptides either containing or lacking the IDE-binding domain. We observed the more pronounced CTF shedding in the TACE-active NOD mice, which represents an inflammatory autoimmune phenotype, but fragmentation was also observed to a lesser extent in the DIO model. Autoantibodies to CTF were detected in both models. Neither exogenous CTF peptide affected IgG-CTF plasma levels, body weight or the conversion of NOD mice to diabetes. The pattern of AdipoR1 fragmentation and autoantibody production under physiological conditions of aging, DIO, and autoimmune diabetes therefore provides insight into the association adiponectin biology and diabetes.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationFrabutt D, Stull N, Pineros AR, et al. Adiponectin receptor fragmentation in mouse models of type 1 and type 2 diabetes. Arch Autoimmune Dis. 2020;1(1):3-13. doi:10.46439/autoimmune.1.002en_US
dc.identifier.urihttps://hdl.handle.net/1805/31409
dc.language.isoen_USen_US
dc.publisherProBiologistsen_US
dc.relation.isversionof10.46439/autoimmune.1.002en_US
dc.relation.journalArchives of Autoimmune Diseasesen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectAdiponectinen_US
dc.subjectPlasmaen_US
dc.subjectInsulin-degrading enzymeen_US
dc.subjectDiet-induced obesityen_US
dc.subjectDiabetesen_US
dc.titleAdiponectin receptor fragmentation in mouse models of type 1 and type 2 diabetesen_US
dc.typeArticleen_US
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