Type 2 diabetes (T2D) is a condition characterized by hyperglycemia and chronic complications. Antidiabetic drugs and lifestyle interventions are the current gold standard therapy for T2D; current therapies, however, can only delay long-term diabetic complications and can additionally be associated with beta cell failure. While the mechanism of beta cell failure is well-studied, little is known about the immunological and inflammatory events associated with antidiabetic agents. Here we studied the effects of three antidiabetic drugs (Metformin, Sitagliptin, and Liraglutide) on immune-relevant pathways in a human beta cell line. Costimulatory molecule expression, cytokine secretion, and gene expression profiles were evaluated at different time points following challenge with the aforementioned antidiabetic agents. Our results showed that these three antidiabetic agents, particularly Sitagliptin, downregulate HLA Class I and II expression and upregulate the immune-regulatory molecules PD-L1 and CTLA4. Metformin and Liraglutide were shown to elicit significantly greater release of TNFa, IL-6, and GM-CSF, while Sitagliptin had a lesser effect on pro-inflammatory cytokine production. Gene expression analysis confirmed the aforementioned observations and also demonstrated upregulation of NOS2, SIRT1, SITR3, POLRMT, MRPL43 and NFkB with antidiabetic agents. We conclude that Sitagliptin most effectively modulates beneficial immune-relevant pathways in a human beta cell line.
Sitagliptin favorably modulates immune-relevant pathways in human beta cells / A.M. Malvandi, C. Loretelli, M. Ben Nasr, G.V. Zuccotti, P. Fiorina. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - 148(2019 Oct).
|Titolo:||Sitagliptin favorably modulates immune-relevant pathways in human beta cells|
MALVANDI, AMIR MOHAMMAD (Primo)
LORETELLI, CRISTIAN (Secondo)
ZUCCOTTI, GIAN VINCENZO (Penultimo)
FIORINA, PAOLO (Ultimo) (Corresponding)
|Parole Chiave:||Human beta cells; Immunity; Liraglutide; Metformin; Sitagliptin; Type 2 diabetes|
|Settore Scientifico Disciplinare:||Settore MED/38 - Pediatria Generale e Specialistica|
|Data di pubblicazione:||ott-2019|
|Data ahead of print / Data di stampa:||20-ago-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.phrs.2019.104405|
|Appare nelle tipologie:||01 - Articolo su periodico|
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