Islets最新文献 - Book学术

Differential expression of mitomiRs in pancreatic islet cells associated with maternal protein restriction. 与母体蛋白限制相关的胰岛细胞mitomir差异表达。

IF 1.7 4区医学

Islets Pub Date : 2026-12-31 Epub Date: 2026-01-01 DOI: 10.1080/19382014.2025.2610590

Cecile Jacovetti, Romano Regazzi

{"title":"Differential expression of mitomiRs in pancreatic islet cells associated with maternal protein restriction.","authors":"Cecile Jacovetti, Romano Regazzi","doi":"10.1080/19382014.2025.2610590","DOIUrl":"10.1080/19382014.2025.2610590","url":null,"abstract":"Objective: Mitochondria are central to energy production and cellular homeostasis. Beyond importing diverse RNAs, they also encode hundreds of their own non-coding RNAs, contributing to a complex and dynamic RNA landscape. Early-life nutritional insults, such as fetal and postnatal protein deficiency, can impair mitochondrial function and increase the long-term diabetes risk. However, the mitochondrial non-coding transcriptome of pancreatic islets, particularly its responsiveness to nutritional cues, remains largely unexplored.Methods: We performed RNA sequencing to profile small non-coding RNAs in mitochondrial fractions of islet cells from offspring of rats exposed to low-protein (LP) or control diets during gestation and lactation and employed mRNA-miRNA network analysis to explore the potential regulatory roles of differentially expressed mitomiRs in LP-exposed pups.Results: Protein deficiency during gestation and lactation led to a profound remodeling of the small non-coding RNA landscape in whole islets, with microRNAs and piRNAs showing the most pronounced changes. In mitochondrial fractions, LP exposure resulted in a striking shift in microRNA composition, with 33 mitomiRs detected in control islets versus 23 in LP-exposed rats, and only 5 shared between groups. Notably, ten mitomiRs were selectively depleted from the cytosol and enriched in mitochondria of LP-exposed islets. Amongst these, miR-10a-5p and miR-126a-5p, are predicted to target genes involved in mitochondrial metabolism and structural organization.Conclusion: Early-life protein restriction triggers a highly selective reorganization of the mitomiR landscape in pancreatic islets. The identified mitomiRs may serve as regulators of mitochondrial function and intracellular signaling, potentially influencing β-cell metabolic coupling and contributing to diabetes susceptibility.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"18 1","pages":"2610590"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A geometry-informed continuous 3D IEQ framework enables more accurate dose estimation in stem cell-derived islet transplantation. 几何信息的连续三维IEQ框架使干细胞来源的胰岛移植的剂量估计更加准确。

IF 1.7 4区医学

Islets Pub Date : 2026-12-31 Epub Date: 2026-05-07 DOI: 10.1080/19382014.2026.2671454

Yu Lu, Jinhui Fang, Zhongyi Jia, Pei Yang, Songtao Bi, Qianyun Liu, Zhe Yu, Jingyi Yin, Limin Chen, Rúben A Ricardo, Anup K Singh, Tongri Liu

{"title":"A geometry-informed continuous 3D IEQ framework enables more accurate dose estimation in stem cell-derived islet transplantation.","authors":"Yu Lu, Jinhui Fang, Zhongyi Jia, Pei Yang, Songtao Bi, Qianyun Liu, Zhe Yu, Jingyi Yin, Limin Chen, Rúben A Ricardo, Anup K Singh, Tongri Liu","doi":"10.1080/19382014.2026.2671454","DOIUrl":"https://doi.org/10.1080/19382014.2026.2671454","url":null,"abstract":"Accurate quantification of islet mass is critical for the preclinical evaluation and therapeutic application of stem cell-derived pancreatic islet organoids. Traditional methods, including Ricordi's islet equivalent (IEQ) approach and its equivalent circle diameter adaptations, often overestimate islet volume due to reliance on maximal diameters and discrete size bins. To address these limitations, we developed an automated image segmentation and three-dimensional modeling framework to quantify individual islet clusters from brightfield images. Clusters were fitted with ellipses and modeled as ellipsoids using rotation about either the minor or major axis, allowing IEQs to be calculated continuously relative to a reference 150 μm spherical islet. Major-axis (prolate) rotation provided the most conservative and physically plausible volume estimates, whereas minor-axis (oblate) rotation and diameter-based approaches systematically overestimated IEQs. Functional assessment with glucose-stimulated insulin secretion assays across multiple size categories demonstrated consistent insulin output for clusters below 250 μm, supporting the reproducibility of our 3D differentiation system. In vivo, streptozotocin-induced diabetic mice transplanted with islet doses based on major-axis modeling exhibited faster and more stable restoration of glycemia compared with groups receiving doses derived from overestimated approaches. These findings establish that major-axis ellipsoid modeling offers a mathematically consistent, conservative, and biologically relevant method for estimating IEQs, providing a practical framework to guide dosing in preclinical studies and supporting the translational development of stem cell-derived islet therapies.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"18 1","pages":"2671454"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Is the intraportal or renal subcapsular space a preferable site for islet allo- and xeno-transplantation? A brief historical review. 门静脉内或肾包膜下间隙是胰岛异体和异体移植的首选位置吗？简要回顾一下历史。

IF 1.7 4区医学

Islets Pub Date : 2026-12-31 Epub Date: 2026-04-22 DOI: 10.1080/19382014.2026.2658317

Sara De Taeye, Rita Bottino, David K C Cooper

{"title":"Is the intraportal or renal subcapsular space a preferable site for islet allo- and xeno-transplantation? A brief historical review.","authors":"Sara De Taeye, Rita Bottino, David K C Cooper","doi":"10.1080/19382014.2026.2658317","DOIUrl":"https://doi.org/10.1080/19382014.2026.2658317","url":null,"abstract":"Diabetes mellitus and end-stage renal disease (ESRD) are major causes of morbidity and mortality worldwide.Pancreatic islet transplantation offers potential insulin independence. Different sites and their suitability for islet transplantation have been investigated, including renal subcapsular and intraportal sites, among others. Various limitations and complications have been reported, such as the number of donor islet species, islet isolation, and site of transplantation. Combining islets and kidney transplantation in diabetic patients suffering from ESRD has several advantages.This review compares the experimental experience of the renal subcapsular and intraportal sites for islet allo- and xeno-transplantation. The subcapsular site appears preferable in rodent models. The intraportal site has been more successful in large animals. Combined islet-kidneys have been suggested as a treatment targeting both ESRD and type 1 diabetes. With our increasing ability to genetically-engineer pigs, and the availability of novel immunosuppressive agents, xenotransplantation is an emerging therapeutic option.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"18 1","pages":"2658317"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Annexin A1 exacerbates islet stellate cell activation by regulating triglyceride catabolism via the PPARα/ACOX1/CYP4a pathway. 膜联蛋白A1通过PPARα/ACOX1/CYP4a途径调节甘油三酯分解代谢，从而加剧胰岛星状细胞的活化。

IF 1.7 4区医学

Islets Pub Date : 2026-12-31 Epub Date: 2026-02-22 DOI: 10.1080/19382014.2026.2633793

Qing Li, Yan Zhang, Tianpei Yu, Li Shi, Qinqin Qiu, Ben Wang, Yiquan Sang, Rui Li, Qian Lv, Jie Wang, Xuekui Liu, Houfa Geng, Peter M Jones, Jun Liang, Wei Xu

{"title":"Annexin A1 exacerbates islet stellate cell activation by regulating triglyceride catabolism via the PPARα/ACOX1/CYP4a pathway.","authors":"Qing Li, Yan Zhang, Tianpei Yu, Li Shi, Qinqin Qiu, Ben Wang, Yiquan Sang, Rui Li, Qian Lv, Jie Wang, Xuekui Liu, Houfa Geng, Peter M Jones, Jun Liang, Wei Xu","doi":"10.1080/19382014.2026.2633793","DOIUrl":"10.1080/19382014.2026.2633793","url":null,"abstract":"Background: Activation of islet stellate cells (ISCs) contributes to islet fibrosis and diabetes progression through excessive extracellular matrix secretion and lipid loss. Annexin A1 (ANXA1) has been reported to modulate lipid metabolism in other tissues, but its role in ISCs remains unclear.Methods: ISCs were isolated from 9-and 28-week-old db/m and db/db mice. Lipid content analysis, qRT‒PCR, and Western blotting were used to assess lipid metabolism-related molecules. ANXA1 expression was analyzed by immunohistochemistry and Western blotting. Recombinant ANXA1 was co-cultured with db/db ISCs to evaluate lipid synthesis and lipolysis. The interaction between ANXA1 and peroxisome proliferator-activated receptor alpha (PPARα) was examined by immunoprecipitation.Results: Activation of ISCs markedly reduced intracellular triglycerides, with decreased Diacylglycerol Acyltransferase 1/2 (DGAT1/2) and increased adipose triglyceride lipase (ATGL) and hormone-sensitive triglyceride lipase (HSL) expression. ANXA1 was detected in islets, MIN6 cells, and their culture supernatants. Recombinant ANXA1 treatment lowered triglyceride levels and upregulated PPARα and its downstream genes, acyl-CoA oxidase 1 (ACOX1) and cytochrome P450 4 A (CYP4A); these effects were enhanced by a PPARα agonist but reversed by inhibition. Immunofluorescence and coimmunoprecipitation confirmed that PPARα acts as a key mediator of ANXA1-regulated triglyceride metabolism in ISCs.Conclusion: ANXA1 promotes ISCs activation by enhancing triglyceride catabolism through the PPARα signaling pathway, suggesting a novel therapeutic target for islet fibrosis.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"18 1","pages":"2633793"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation. 人和小鼠再生巨噬细胞增强β细胞的存活、功能和增殖。

IF 1.7 4区医学

Islets Pub Date : 2026-12-31 Epub Date: 2026-05-03 DOI: 10.1080/19382014.2026.2659457

Mahdis Monajemi, Alexandra S Craciun, Qing Huang, Lei Dai, Majid Mojibian, Sarah Q Crome, C Bruce Verchere, Megan K Levings

{"title":"Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation.","authors":"Mahdis Monajemi, Alexandra S Craciun, Qing Huang, Lei Dai, Majid Mojibian, Sarah Q Crome, C Bruce Verchere, Megan K Levings","doi":"10.1080/19382014.2026.2659457","DOIUrl":"https://doi.org/10.1080/19382014.2026.2659457","url":null,"abstract":"Aims: Type 1 diabetes is caused by immune-mediated destruction of beta cells. Interestingly, individuals with long-standing type 1 diabetes have residual beta cells, suggesting regenerative mechanisms may help beta cell survival. Islet-resident macrophages have an important role in diabetes, and can adopt a tissue-regenerating phenotype that may support beta cells. However, the roles of macrophages in beta cell survival, function, and proliferation remain poorly defined. This study aimed to elucidate how macrophage subtypes influence beta cell survival, function, and proliferation.Methods: Mouse and human islets were isolated from the pancreas and co-cultured in vitro with macrophages. To investigate whether macrophages enhance beta cell survival and function, apoptosis was measured using flow cytometry, and insulin secretion was assessed via glucose-stimulated insulin secretion assays. We also examined whether macrophages increased beta cell proliferation in the presence of harmine, a DYRK1A inhibitor. Finally, we evaluated the effect of islet co-culture on macrophage phenotype by flow cytometry and cytokine secretion analysis.Results: We found that regenerative, but not pro-inflammatory, macrophages enhanced beta cell survival and function through mechanisms that did not require direct cell contact. Direct contact between macrophages and islets promoted a macrophage regenerative phenotype characterized by increased CD206 expression and secretion of anti-inflammatory factors. Additionally, regenerative macrophages promoted beta cell proliferation in the presence of harmine.Conclusions: Our findings demonstrate that regenerative macrophages support pancreatic beta cell survival, function, and proliferation. Harnessing the regenerative properties of macrophages could offer a novel strategy to promote beta cell survival and function.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"18 1","pages":"2659457"},"PeriodicalIF":1.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of HNF4α knockout in beta cells is age and sex dependent. HNF4α基因敲除对β细胞的影响具有年龄和性别依赖性。

IF 1.7 4区医学

Islets Pub Date : 2025-12-31 Epub Date: 2025-09-29 DOI: 10.1080/19382014.2025.2552549

Catharina B P Villaca, Viviane R Oliveira, Gustavo J Santos, Fernanda Ortis

{"title":"The effect of HNF4α knockout in beta cells is age and sex dependent.","authors":"Catharina B P Villaca, Viviane R Oliveira, Gustavo J Santos, Fernanda Ortis","doi":"10.1080/19382014.2025.2552549","DOIUrl":"10.1080/19382014.2025.2552549","url":null,"abstract":"HNF4α is important for beta cells' ability to adequately secrete insulin in response to glucose concentration and endoplasmic reticulum (ER) homeostasis. In humans, HNF4α mutations are responsible for Diabetes mellitus subtype MODY1, which has an age-determining onset. Additionally, in other forms of DM, there is evidence that sex can influence beta cell dysfunction, with possible involvement of ER stress pathways. Thus, we assessed the influence of sex and age on beta-cell dysfunction induced by HNF4α absence. We used an animal model with specific beta cells KO of HNF4α, induced after birth (Ins. CRE HNF4αloxP/loxP). Glucose intolerance is observed after 10 d of KO induction, at 50 d of age, with KO males (MKO) displaying more severe glucose intolerance than KO females (FKO). The percentage of insulin-positive cells in KO mice islets is lower compared to Control at all ages evaluated, with MKO mice showing a more pronounced decline at later ages compared to FKO. Both KO groups exhibited reduced beta cell mass and increased α-cell mass, which was more pronounced in MKO. ER stress was induced in both KO groups; however, ER stress-mediated apoptosis was observed only in MKO. FKO mice show evidence of beta cell differentiated state loss. In summary, beta cell loss in HNF4α-KO is influenced by sex and age, involves induction of ER stress, and is more severe in males, where ER stress-induced beta cell death is observed. Partial protection observed in females seems to involve dedifferentiation of beta cells.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"17 1","pages":"2552549"},"PeriodicalIF":1.7,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction. 修正。

IF 1.7 4区医学

Islets Pub Date : 2025-12-31 Epub Date: 2025-09-07 DOI: 10.1080/19382014.2025.2557668

引用次数: 0

The effects of free fatty acid-free bovine serum albumin and palmitate on pancreatic β-cell function. 无脂肪酸牛血清白蛋白和棕榈酸酯对胰腺β细胞功能的影响。

IF 1.9 4区医学

Islets Pub Date : 2025-12-01 Epub Date: 2025-03-16 DOI: 10.1080/19382014.2025.2479911

Katherine Sentjens, Renjitha Pillai, Jamie W Joseph

{"title":"The effects of free fatty acid-free bovine serum albumin and palmitate on pancreatic β-cell function.","authors":"Katherine Sentjens, Renjitha Pillai, Jamie W Joseph","doi":"10.1080/19382014.2025.2479911","DOIUrl":"10.1080/19382014.2025.2479911","url":null,"abstract":"Pancreatic β-cells release insulin in response to fluctuations in plasma glucose, amino acids, and free fatty acids (FFA). Clonal cell lines and isolated islets serve as essential early models for studying the impact of nutrients and evaluating potential therapies to address β-cell dysfunction. Acute and chronic changes in FFA levels have been shown to have positive and negative effects on β-cell function both in vivo and in vitro. A key problem in comparing islet lipid studies from different laboratories is that a wide variety of methods are used to isolate, culture, and assess islet function. The current study compares bovine serum albumin (BSA) types and lipid preparation methods in clonal 832/13 cells and human islets. Changing the percentage and culture conditions when using FFA-free BSA can negatively affect β-cell function compared to regular BSA. Preparing palmitate with FFA-free BSA can rescue insulin secretion compared to treating cells alone with FFA-free BSA. Different methods of preparing palmitate can have unique effects on insulin secretion. Overall, interpreting the effects of lipids on β-cell function is complicated by a number of variables that need to be controlled for in islet experiments.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"17 1","pages":"2479911"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crosstalk between the aryl hydrocarbon receptor and hypoxia-inducible factor 1α pathways in human islet models. 人胰岛模型中芳烃受体与缺氧诱导因子1α通路的串扰。

IF 1.9 4区医学

Islets Pub Date : 2025-12-01 Epub Date: 2025-07-17 DOI: 10.1080/19382014.2025.2526871

Noa Gang, Kyle A van Allen, William G Willmore, Francis C Lynn, Jennifer E Bruin

{"title":"Crosstalk between the aryl hydrocarbon receptor and hypoxia-inducible factor 1α pathways in human islet models.","authors":"Noa Gang, Kyle A van Allen, William G Willmore, Francis C Lynn, Jennifer E Bruin","doi":"10.1080/19382014.2025.2526871","DOIUrl":"10.1080/19382014.2025.2526871","url":null,"abstract":"Background: We previously showed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD - a persistent organic pollutant) activates the aryl hydrocarbon receptor (AHR) in pancreatic islets. The AHR is known to crosstalk with hypoxia-inducible factor 1α (HIF1α) in other cell types but AHR-HIF1α crosstalk has not been previously examined in islet cells. Islet cell function is sensitive to hypoxia; we hypothesize that AHR activation by environmental pollutant(s) will interfere with the HIF1α pathway response in islets, which may be detrimental to islet cell function and survival during periods of hypoxia.Methods: We assessed AHR-HIF1α crosstalk by treating human donor islets and stem cell-derived islets (SC-islets) with 10 nM TCDD ± 1% O2 and measuring gene expression of downstream targets of AHR (e.g. CYP1A1) and HIF1α (e.g. HMOX1).Results: In SC-islets, co-treatment with TCDD + hypoxia consistently suppressed CYP1A1 induction compared with TCDD treatment alone. In human islets, TCDD + hypoxia co-treatment suppressed CYP1A1 induction, but only in 2 of 6 donors. Both SC-islets and human donor islets displayed hypoxia-mediated suppression of glucose-6-phosphate catalytic subunit 2 (G6PC2) expression. Glucose-stimulated insulin secretion (GSIS) in human donor islets was impaired by hypoxia exposure, but unaffected by TCDD exposure.Conclusion: Our study shows consistent AHR-HIF1α crosstalk in SC-islets and variable crosstalk in primary human islets, depending on the donor. In both cell models, hypoxia exposure interfered with activation of the AHR pathway by TCDD but there was no evidence that AHR activation interfered with the HIF1α pathway. In summary, our data show that co-exposure to an environmental pollutant and hypoxia results in molecular crosstalk in islets.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"17 1","pages":"2526871"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CK2 regulates somatostatin expression in pancreatic delta cells. CK2调节胰腺三角洲细胞中生长抑素的表达。

IF 1.9 4区医学

Islets Pub Date : 2025-12-01 Epub Date: 2025-06-05 DOI: 10.1080/19382014.2025.2515332

Selina Wrublewsky, Annika Clemenz, Anne S Boewe, Cedric Wilden, Caroline Bickelmann, Claudia Götz, Patrick E MacDonald, Matthias W Laschke, Emmanuel Ampofo

{"title":"CK2 regulates somatostatin expression in pancreatic delta cells.","authors":"Selina Wrublewsky, Annika Clemenz, Anne S Boewe, Cedric Wilden, Caroline Bickelmann, Claudia Götz, Patrick E MacDonald, Matthias W Laschke, Emmanuel Ampofo","doi":"10.1080/19382014.2025.2515332","DOIUrl":"10.1080/19382014.2025.2515332","url":null,"abstract":"Pancreatic and duodenal homeobox protein (PDX)1 is a major transcription factor for the regulation of insulin, glucagon and somatostatin (SST) expression. PDX1 is phosphorylated by CK2 and inhibition of this kinase results in an increased insulin and decreased glucagon secretion. Therefore, we speculated in this study that CK2 also affects SST expression. To test this, we analyzed the effects of the two CK2 inhibitors CX-4945 and SGC as well as of PDX1 overexpression on SST expression and secretion in RIN14B cells by qRT-PCR, luciferase assays, Western blot and ELISA. SST expression and secretion were additionally assessed in isolated murine and human islets exposed to the CK2 inhibitors. Moreover, we determined the expression and secretion of the pancreatic endocrine hormones in CX-4945-treated mice. We found a suppressed SST expression in RIN14B cells due to a methylated SST promoter, which could be abolished by DNA demethylation. Under these conditions, we showed that CK2 inhibition increases SST gene expression and secretion. Additional experiments with overexpression of a CK2-phosphorylation mutant of PDX1 verified that SST expression is regulated by CK2. The exposure of isolated murine and human islets to CX-4945 or SGC as well as the treatment of mice with CX-4945 revealed that CK2 also regulates SST expression under physiological conditions. Taken together, these findings not only demonstrate that CK2 controls SST expression in pancreatic δ-cells but also emphasize the crucial role of this kinase in regulating the main hormones of the endocrine pancreas.","PeriodicalId":14671,"journal":{"name":"Islets","volume":"17 1","pages":"2515332"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0