Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33
Galectin-3 (Gal-3) has diverse roles in inflammatory and autoimmune diseases. There is evidence that Gal-3 plays a role in both type 1 and type 2 diabetes. While the role of Gal-3 expression in immune cells invading the pancreatic islets in the experimental model of type 1 diabetes mellitus has been...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:5e0b18209fee469b9c0d6335ceac4f002021-11-05T12:17:46ZTransgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-331663-981210.3389/fphar.2021.714683https://doaj.org/article/5e0b18209fee469b9c0d6335ceac4f002021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.714683/fullhttps://doaj.org/toc/1663-9812Galectin-3 (Gal-3) has diverse roles in inflammatory and autoimmune diseases. There is evidence that Gal-3 plays a role in both type 1 and type 2 diabetes. While the role of Gal-3 expression in immune cells invading the pancreatic islets in the experimental model of type 1 diabetes mellitus has been already studied, the importance of the overexpression of Gal-3 in the target β cells is not defined. Therefore, we used multiple low doses of streptozotocin (MLD–STZ)–induced diabetes in C57Bl/6 mice to analyze the effect of transgenic (TG) overexpression of Gal-3 in β cells. Our results demonstrated that the overexpression of Gal-3 protected β cells from apoptosis and attenuated MLD–STZ–induced hyperglycemia, glycosuria, and ketonuria. The cellular analysis of pancreata and draining lymph nodes showed that Gal-3 overexpression significantly decreased the number of pro-inflammatory cells without affecting the presence of T-regulatory cells. As the application of exogenous interleukin 33 (IL-33) given from the beginning of MLD–STZ diabetes induction attenuates the development of disease, by increasing the presence of regulatory FoxP3+ ST2+ cells, we evaluated the potential synergistic effect of the exogenous IL-33 and TG overexpression of Gal-3 in β cells at the later stage of diabetogenesis. The addition of IL-33 potentiated the survival of β cells and attenuated diabetes even when administered later, after the onset of hyperglycemia (12–18 days), suggesting that protection from apoptosis and immunoregulation by IL-33 may attenuate type 1 diabetes.Nemanja JovicicIvica PetrovicNada PejnovicBiljana LjujicMarina Miletic KovacevicSladjana PavlovicIlija JefticAleksandar DjukicIvan SrejovicVladimir JakovljevicVladimir JakovljevicMiodrag L LukicMiodrag L LukicFrontiers Media S.A.articlegalectin-3type 1 diabetes mellitus (T1D)β cellsinterleukin 33 (IL-33)regulatory T cells (T reg)Therapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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galectin-3 type 1 diabetes mellitus (T1D) β cells interleukin 33 (IL-33) regulatory T cells (T reg) Therapeutics. Pharmacology RM1-950 |
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galectin-3 type 1 diabetes mellitus (T1D) β cells interleukin 33 (IL-33) regulatory T cells (T reg) Therapeutics. Pharmacology RM1-950 Nemanja Jovicic Ivica Petrovic Nada Pejnovic Biljana Ljujic Marina Miletic Kovacevic Sladjana Pavlovic Ilija Jeftic Aleksandar Djukic Ivan Srejovic Vladimir Jakovljevic Vladimir Jakovljevic Miodrag L Lukic Miodrag L Lukic Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33 |
| description |
Galectin-3 (Gal-3) has diverse roles in inflammatory and autoimmune diseases. There is evidence that Gal-3 plays a role in both type 1 and type 2 diabetes. While the role of Gal-3 expression in immune cells invading the pancreatic islets in the experimental model of type 1 diabetes mellitus has been already studied, the importance of the overexpression of Gal-3 in the target β cells is not defined. Therefore, we used multiple low doses of streptozotocin (MLD–STZ)–induced diabetes in C57Bl/6 mice to analyze the effect of transgenic (TG) overexpression of Gal-3 in β cells. Our results demonstrated that the overexpression of Gal-3 protected β cells from apoptosis and attenuated MLD–STZ–induced hyperglycemia, glycosuria, and ketonuria. The cellular analysis of pancreata and draining lymph nodes showed that Gal-3 overexpression significantly decreased the number of pro-inflammatory cells without affecting the presence of T-regulatory cells. As the application of exogenous interleukin 33 (IL-33) given from the beginning of MLD–STZ diabetes induction attenuates the development of disease, by increasing the presence of regulatory FoxP3+ ST2+ cells, we evaluated the potential synergistic effect of the exogenous IL-33 and TG overexpression of Gal-3 in β cells at the later stage of diabetogenesis. The addition of IL-33 potentiated the survival of β cells and attenuated diabetes even when administered later, after the onset of hyperglycemia (12–18 days), suggesting that protection from apoptosis and immunoregulation by IL-33 may attenuate type 1 diabetes. |
| format |
article |
| author |
Nemanja Jovicic Ivica Petrovic Nada Pejnovic Biljana Ljujic Marina Miletic Kovacevic Sladjana Pavlovic Ilija Jeftic Aleksandar Djukic Ivan Srejovic Vladimir Jakovljevic Vladimir Jakovljevic Miodrag L Lukic Miodrag L Lukic |
| author_facet |
Nemanja Jovicic Ivica Petrovic Nada Pejnovic Biljana Ljujic Marina Miletic Kovacevic Sladjana Pavlovic Ilija Jeftic Aleksandar Djukic Ivan Srejovic Vladimir Jakovljevic Vladimir Jakovljevic Miodrag L Lukic Miodrag L Lukic |
| author_sort |
Nemanja Jovicic |
| title |
Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33 |
| title_short |
Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33 |
| title_full |
Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33 |
| title_fullStr |
Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33 |
| title_full_unstemmed |
Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33 |
| title_sort |
transgenic overexpression of galectin-3 in pancreatic β cells attenuates hyperglycemia in mice: synergistic antidiabetic effect with exogenous il-33 |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/5e0b18209fee469b9c0d6335ceac4f00 |
| work_keys_str_mv |
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