TY - JOUR
T1 - Liraglutide compromises pancreatic β cell function in a humanized mouse model
AU - Abdulreda, Midhat H.
AU - Rodriguez-Diaz, Rayner
AU - Caicedo, Alejandro
AU - Berggren, Per Olof
N1 - Funding Information:
This work was supported by funds from the Diabetes Research Institute Foundation (DRIF), grants from the NIH/NIDDK (F32DK083226/DK097194/R01DK084321), the Swedish Diabetes Association Funds, the Swedish Research Council, Novo Nordisk Foundation, the Family Erling-Persson Foundation, Strategic Research Program in Diabetes at Karolinska Institutet, the ERC-2013-AdG 338936-BetaImage, the Family Knut and Alice Wallenberg Foundation, Skandia Insurance Company Ltd, Diabetes and Wellness Foundation, the Bert von Kantzow Foundation, and the Stichting af Jochnick Foundation. P.-O.B. is cofounder and CEO of Biocrine, an unlisted biotech company that is using the anterior chamber of the eye technique as a research tool. M.H.A. is consultant for the same company. We thank pRED at F. Hoffmann- La Roche, Basel, Switzerland, for bioanalytic and islet morphology analyses and support of this study. We also thank Dr. April Mann from the University of Miami''s Writing Center for feedback on the manuscript. We acknowledge the organ donors and their families for enabling our research with human pancreatic islets.
PY - 2016/3/8
Y1 - 2016/3/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cmet.2016.01.009
DO - 10.1016/j.cmet.2016.01.009
M3 - Article
C2 - 26876561
AN - SCOPUS:84960852527
VL - 23
SP - 541
EP - 546
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 3
ER -