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Reports that DPP-4 may be associated with glucagon in the secretory granules of the pancreatic -cell first emerged in 1993, when positive staining in pig islets was shown using immunohistochemical and enzyme histochemical techniques (96), but the pancreatic localization of DPP-4 has also been unequivocally demonstrated more recently using molecular biological techniques (9799)

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30 Despite the well-established clinical cardiovascular benefits of GLP-1 RAs, the chronotropic effect may limit the use of GLP-1RAs in some patients with underlying heart conditions

*Correspondence: Natalie Jane Michael, [email protected] These authors contributed equally to this work and share first authorship Disclaimer All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers