2023, Leciejewska, Natalia, Pruszyńska-Oszmałek, Ewa, Sassek, Maciej, Głowacki, M., Lehmann, T., Rekas-Dudziak, A., Nogowski, Leszek, Nowak, Krzysztof W., Kołodziejski, Paweł

2025, Czyzniewski, B., Chmielowiec, J., Pruszyńska-Oszmałek, Ewa, Hajduk-Warchol, M., Chmielowiec, K., Kołodziejski, Paweł, Huzarski, T., Checinska-Maciejewska, Z., Kowalski, M.T., Szczap, E., Gibas-Dorna, M.

2023, Pusch, Emily, Krążek, Małgorzata, Wojciechowicz, Tatiana, Sassek, Maciej, Kołodziejski, Paweł, Strowski, Mathias, Nowak, Krzysztof W., Skrzypski, Marek

GIP_HUMAN [22–51] is a recently discovered peptide that shares the same precursor molecule with glucose-dependent insulinotropic polypeptide (GIP). In vivo, chronic infusion of GIP_HUMAN [22–51] in ApoE−/− mice enhanced the development of aortic atherosclerotic lesions and upregulated inflammatory and proatherogenic proteins. In the present study, we evaluate the effects of GIP_HUMAN [22–51] on insulin mRNA expression and secretion in insulin-producing INS-1E cells and isolated rat pancreatic islets. Furthermore, we characterize the influence of GIP_HUMAN [22–51] on cell proliferation and death and on Nf-kB nuclear translocation. Rat insulin-producing INS-1E cells and pancreatic islets, isolated from male Wistar rats, were used in this study. Gene expression was evaluated using real-time PCR. Cell proliferation was studied using a BrdU incorporation assay. Cell death was quantified by evaluating histone-complexed DNA fragments. Insulin secretion was determined using an ELISA test. Nf-kB nuclear translocation was detected using immunofluorescence. GIP_HUMAN [22–51] suppressed insulin (Ins1 and Ins2) in INS-1E cells and pancreatic islets. Moreover, GIP_HUMAN [22–51] promoted the translocation of NF-κB from cytoplasm to the nucleus. In the presence of a pharmacological inhibitor of NF-κB, GIP_HUMAN [22–51] was unable to suppress Ins2 mRNA expression. Moreover, GIP_HUMAN [22–51] downregulated insulin secretion at low (2.8 mmol/L) but not high (16.7 mmol/L) glucose concentration. By contrast, GIP_HUMAN [22–51] failed to affect cell proliferation and apoptosis. We conclude that GIP_HUMAN [22–51] suppresses insulin expression and secretion in pancreatic β cells without affecting β cell proliferation or apoptosis. Notably, the effects of GIP_HUMAN [22–51] on insulin secretion are glucose-dependent.

2023, Chęcińska, Aleksandra, Chęcińska-Maciejewska, Zuzanna, Wojciechowska, Małgorzata, Ciborek, Andrzej, Kołodziejski, Paweł, Pruszyńska-Oszmałek, Ewa, Gibas-Dorna, Magdalena