title: Liraglutide Compromises Pancreatic β Cell Function in a Humanized Mouse Model.
abstract: Incretin mimetics are frequently used in the treatment of type 2 diabetes because they potentiate β cell response to glucose. Clinical evidence showing short-term benefits of such therapeutics (e.g., liraglutide) is abundant; however, there have been several recent reports of unexpected complications in association with incretin mimetic therapy. Importantly, clinical evidence on the potential effects of such agents on the β cell and islet function during long-term, multiyear use remains lacking. We now show that prolonged daily liraglutide treatment of >200 days in humanized mice, transplanted with human pancreatic islets in the anterior chamber of the eye, is associated with compromised release of human insulin and deranged overall glucose homeostasis. These findings raise concern about the chronic potentiation of β cell function through incretin mimetic therapy in diabetes.
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10th Avenue, Miami, FL 33136, USA. Electronic address: mabdulreda@miami.edu.
authors.forename: Midhat H
authors.initials: MH
authors.lastname: Abdulreda
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, 1580 NW 10th Avenue, Miami, FL 33136, USA.
authors.forename: Rayner
authors.initials: R
authors.lastname: Rodriguez-Diaz
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, 1580 NW 10th Avenue, Miami, FL 33136, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Caicedo
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10th Avenue, Miami, FL 33136, USA; The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm SE-17176, Sweden. Electronic address: per-olof.berggren@ki.se.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D005123:Eye / Q000473:pathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D000069450:Liraglutide / Q000494:pharmacology*; D051379:Mice
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000069450:Liraglutide