biostudies-literatureGiusti LUnion’s Horizon 2020 research and innovation programItalian Ministry of University and ResearchNIDDK NIH HHSInnovative Medicines Initiative 2 Joint Undertaking“EFPIA”, “JDRF”, and “The Leona M. and Harry B. Helmsley Charitable Trust”2465https://www.ebi.ac.uk/biostudies/studies/S-EPMC9368307biostudies-literatureUnknown11(15)Metformin, a drug widely used in type 2 diabetes (T2D), has been shown to protect human β-cells exposed to gluco- and/or lipotoxic conditions and those in islets from T2D donors. We assessed whether metformin could relieve the human β-cell stress induced by pro-inflammatory cytokines (which mediate β-cells damage in type 1 diabetes, T1D) and investigated the underlying mechanisms using shotgun proteomics. Human islets were exposed to 50 U/mL interleukin-1β plus 1000 U/mL interferon-γ for 48 h, with or without 2.4 µg/mL metformin. Glucose-stimulated insulin secretion (GSIS) and caspase 3/7 activity were studied, and a shotgun label free proteomics analysis was performed. Metformin prevented the reduction of GSIS and the activation of caspase 3/7 induced by cytokines. Proteomics analysis ideCellsThe Protective Action of Metformin against Pro-Inflammatory Cytokine-Induced Human Islet Cell Damage and the Mechanisms Involved.PMC9368307115,797U01 DK1277862017KAM2R5_005945,268Ronci MDel Guerra SZuccarini MTesi MCiregia FLucacchini ACnop MMarselli LGiusti LDe Luca CMarchetti PZallocco LTrerotola MMazzoni MRSuleiman MEizirik DLfalseThe Protective Action of Metformin against Pro-Inflammatory Cytokine-Induced Human Islet Cell Damage and the Mechanisms Involved.Metformin, a drug widely used in type 2 diabetes (T2D), has been shown to protect human β-cells exposed to gluco- and/or lipotoxic conditions and those in islets from T2D donors. We assessed whether metformin could relieve the human β-cell stress induced by pro-inflammatory cytokines (which mediate β-cells damage in type 1 diabetes, T1D) and investigated the underlying mechanisms using shotgun proteomics. Human islets were exposed to 50 U/mL interleukin-1β plus 1000 U/mL interferon-γ for 48 h, with or without 2.4 µg/mL metformin. Glucose-stimulated insulin secretion (GSIS) and caspase 3/7 activity were studied, and a shotgun label free proteomics analysis was performed. Metformin prevented the reduction of GSIS and the activation of caspase 3/7 induced by cytokines. Proteomics analysis ide2022-01-01T00:00:00Z2022 Aug2026-05-08T03:12:57.713Z2025-02-19T03:23:57.933ZS-EPMC93683073595430910.3390/cells11152465