Bingjie Fan, Lili Yin, A 'ni Wang, Fei Li, Shuguang Han
{"title":"PIM1通过灭活JNK/p38信号通路，增强PINK1/ parkinson介导的有丝分裂，从而增强胰岛素分泌，抑制高糖诱导的胰腺β-细胞铁凋亡。","authors":"Bingjie Fan, Lili Yin, A 'ni Wang, Fei Li, Shuguang Han","doi":"10.1016/j.tice.2025.102722","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM), a chronic metabolic disease, is characterized by long-term hyperglycemia resulting from the defect of insulin production and insulin resistance. The damage and dysfunction of pancreatic β-cells is a main link in DM development.</p><p><strong>Methods: </strong>In this work, pancreatic β-cell line INS-1E cells were exposed to 30 mM glucose for 48 h to construct an in vitro DM model. For gain-of-function experiments, HG-treated INS-1E cells were transfected with Oe-PIM1 to thoroughly discuss the biological role of PIM1 in HG-injured pancreatic β-cells. Furthermore, to probe into whether JNK/p38 signaling involved in the protective role of PIM1 in HG-injured pancreatic β-cells, HG-treated INS-1E cells were pre-treated with a JNK activator anisomycin (0.01 μM) for 1 h for rescue experiments.</p><p><strong>Results: </strong>It was verified that HG treatment obviously downregulated PIM1 expression in INS-1E cells. PIM1 overexpression enhanced insulin secretion, inhibited ferroptosis and strengthened PINK1/Parkin-mediated mitophagy of HG-treated INS-1E cells. PIM1 overexpression inactivated JNK/p38 signaling pathway in HG-treated INS-1E cells. Activation of JNK/p38 signaling pathway partially abolished the strengthening effects of PIM1 overexpression on PINK1/Parkin-mediated mitophagy in HG-treated INS-1E cells. Upregulation of PIM1 strengthened PINK1/Parkin-mediated mitophagy in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway. Besides, activation of JNK/p38 signaling pathway partially abolished the enhancing effects of PIM1 overexpression on insulin secretion and the suppressive effects of PIM1 overexpression on ferroptosis in HG-treated INS-1E cells. Upregulation of PIM1 enhanced insulin secretion and inhibited ferroptosis in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway.</p><p><strong>Conclusion: </strong>In a word, upregulation of PIM1 may alleviate HG-induced pancreatic β-cell injury through strengthening PINK1/Parkin-mediated mitophagy via inactivating JNK/p38 signaling pathway.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"102722"},"PeriodicalIF":2.7000,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PIM1 enhances insulin secretion and inhibits ferroptosis of high glucose-induced pancreatic β-cells through strengthening PINK1/Parkin-mediated mitophagy via inactivating JNK/p38 signaling pathway.\",\"authors\":\"Bingjie Fan, Lili Yin, A 'ni Wang, Fei Li, Shuguang Han\",\"doi\":\"10.1016/j.tice.2025.102722\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Diabetes mellitus (DM), a chronic metabolic disease, is characterized by long-term hyperglycemia resulting from the defect of insulin production and insulin resistance. The damage and dysfunction of pancreatic β-cells is a main link in DM development.</p><p><strong>Methods: </strong>In this work, pancreatic β-cell line INS-1E cells were exposed to 30 mM glucose for 48 h to construct an in vitro DM model. For gain-of-function experiments, HG-treated INS-1E cells were transfected with Oe-PIM1 to thoroughly discuss the biological role of PIM1 in HG-injured pancreatic β-cells. Furthermore, to probe into whether JNK/p38 signaling involved in the protective role of PIM1 in HG-injured pancreatic β-cells, HG-treated INS-1E cells were pre-treated with a JNK activator anisomycin (0.01 μM) for 1 h for rescue experiments.</p><p><strong>Results: </strong>It was verified that HG treatment obviously downregulated PIM1 expression in INS-1E cells. PIM1 overexpression enhanced insulin secretion, inhibited ferroptosis and strengthened PINK1/Parkin-mediated mitophagy of HG-treated INS-1E cells. PIM1 overexpression inactivated JNK/p38 signaling pathway in HG-treated INS-1E cells. Activation of JNK/p38 signaling pathway partially abolished the strengthening effects of PIM1 overexpression on PINK1/Parkin-mediated mitophagy in HG-treated INS-1E cells. Upregulation of PIM1 strengthened PINK1/Parkin-mediated mitophagy in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway. Besides, activation of JNK/p38 signaling pathway partially abolished the enhancing effects of PIM1 overexpression on insulin secretion and the suppressive effects of PIM1 overexpression on ferroptosis in HG-treated INS-1E cells. Upregulation of PIM1 enhanced insulin secretion and inhibited ferroptosis in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway.</p><p><strong>Conclusion: </strong>In a word, upregulation of PIM1 may alleviate HG-induced pancreatic β-cell injury through strengthening PINK1/Parkin-mediated mitophagy via inactivating JNK/p38 signaling pathway.</p>\",\"PeriodicalId\":23201,\"journal\":{\"name\":\"Tissue & cell\",\"volume\":\"93 \",\"pages\":\"102722\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-01-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tissue & cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.tice.2025.102722\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ANATOMY & MORPHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.tice.2025.102722","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
PIM1 enhances insulin secretion and inhibits ferroptosis of high glucose-induced pancreatic β-cells through strengthening PINK1/Parkin-mediated mitophagy via inactivating JNK/p38 signaling pathway.
Background: Diabetes mellitus (DM), a chronic metabolic disease, is characterized by long-term hyperglycemia resulting from the defect of insulin production and insulin resistance. The damage and dysfunction of pancreatic β-cells is a main link in DM development.
Methods: In this work, pancreatic β-cell line INS-1E cells were exposed to 30 mM glucose for 48 h to construct an in vitro DM model. For gain-of-function experiments, HG-treated INS-1E cells were transfected with Oe-PIM1 to thoroughly discuss the biological role of PIM1 in HG-injured pancreatic β-cells. Furthermore, to probe into whether JNK/p38 signaling involved in the protective role of PIM1 in HG-injured pancreatic β-cells, HG-treated INS-1E cells were pre-treated with a JNK activator anisomycin (0.01 μM) for 1 h for rescue experiments.
Results: It was verified that HG treatment obviously downregulated PIM1 expression in INS-1E cells. PIM1 overexpression enhanced insulin secretion, inhibited ferroptosis and strengthened PINK1/Parkin-mediated mitophagy of HG-treated INS-1E cells. PIM1 overexpression inactivated JNK/p38 signaling pathway in HG-treated INS-1E cells. Activation of JNK/p38 signaling pathway partially abolished the strengthening effects of PIM1 overexpression on PINK1/Parkin-mediated mitophagy in HG-treated INS-1E cells. Upregulation of PIM1 strengthened PINK1/Parkin-mediated mitophagy in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway. Besides, activation of JNK/p38 signaling pathway partially abolished the enhancing effects of PIM1 overexpression on insulin secretion and the suppressive effects of PIM1 overexpression on ferroptosis in HG-treated INS-1E cells. Upregulation of PIM1 enhanced insulin secretion and inhibited ferroptosis in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway.
Conclusion: In a word, upregulation of PIM1 may alleviate HG-induced pancreatic β-cell injury through strengthening PINK1/Parkin-mediated mitophagy via inactivating JNK/p38 signaling pathway.
期刊介绍：
Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed.
Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.
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