Species-Related Differences in the Proteome of Rat and Human Pancreatic Beta Cells

Martens, Guy

doi:10.1155/2015/549818

Cited by 15 publications

(10 citation statements)

References 31 publications

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“…The documented insulin expression and secretion of NT-3 cells warrants evaluation as a potential model for human pancreatic beta cells. Until now, no such human model exists and most basic diabetes research has been performed in a rat insulinoma cell line (INS1E), with obvious limitations such as differences in protein expression and functional status between human and rodent islet cells (34,35). The only human cell line derived from an insulinoma (called CM) has already lost insulin expression and secretion during in vitro culture (36).…”

Section: Discussionmentioning

confidence: 99%

Establishment of the First Well-differentiated Human Pancreatic Neuroendocrine Tumor Model

Benten

Behrang

Unrau

et al. 2018

Molecular Cancer Research

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Clinical options for systemic therapy of neuroendocrine tumors (NET) are limited. Development of new drugs requires suitable representative and model systems. So far, the unavailability of a human model with a well-differentiated phenotype and typical growth characteristics has impaired preclinical research in NET. Herein, we establish and characterize a lymph node-derived cell line (NT-3) from a male patient with well-differentiated pancreatic NET. Neuroendocrine differentiation and tumor biology was compared with existing NET cell lines BON and QGP-1. growth was assessed in a xenograft mouse model. The neuroendocrine identity of NT-3 was verified by expression of multiple NET-specific markers, which were highly expressed in NT-3 compared with BON and QGP-1. In addition, NT-3 expressed and secreted insulin. Until now, this well-differentiated phenotype is stable since 58 passages. The proliferative labeling index, measured by Ki-67, of 14.6% ± 1.0% in NT-3 is akin to the original tumor (15%-20%), and was lower than in BON (80.6% ± 3.3%) and QGP-1 (82.6% ± 1.0%). NT-3 highly expressed somatostatin receptors (SSTRs: 1, 2, 3, and 5). Upon subcutaneous transplantation of NT-3 cells, recipient mice developed tumors with an efficient tumor take rate (94%) and growth rate (139% ± 13%) by 4 weeks. Importantly, morphology and neuroendocrine marker expression of xenograft tumors resembled the original human tumor. High expression of somatostatin receptors and a well-differentiated phenotype as well as a slow growth rate qualify the new cell line as a relevant model to study neuroendocrine tumor biology and to develop new tumor treatments. .

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Section: Discussionmentioning

confidence: 99%

Establishment of the First Well-differentiated Human Pancreatic Neuroendocrine Tumor Model

Benten

Behrang

Unrau

et al. 2018

Molecular Cancer Research

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“…All experiments were performed in human pancreatic islets and the human insulinproducing cell line EndoC-βH1 [24], increasing their translational potential [25][26][27][28]. The data obtained indicate that IFNα is a crucial mediator of excessive inflammation and ER stress in the early steps of type 1 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Interferon-α mediates human beta cell HLA class I overexpression, endoplasmic reticulum stress and apoptosis, three hallmarks of early human type 1 diabetes

et al. 2017

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Aims/hypothesis Three hallmarks of the pancreatic islets in early human type 1 diabetes are overexpression of HLA class I, endoplasmic reticulum (ER) stress and beta cell apoptosis. The mediators of these phenomena remain to be defined. The type I interferon IFNα is expressed in human islets from type 1 diabetes patients and mediates HLA class I overexpression. We presently evaluated the mechanisms involved in IFNα-induced HLA class I expression in human beta cells and determined whether this cytokine contributes to ER stress and apoptosis. Methods IFNα-induced inflammation, ER stress and apoptosis were evaluated by RT-PCR, western blot, immunofluorescence and nuclear dyes, and proteins involved in type I interferon signalling were inhibited by small interfering RNAs. All experiments were performed in human islets or human EndoC-βH1 cells.Results IFNα upregulates HLA class I, inflammation and ER stress markers in human beta cells via activation of the candidate gene TYK2, and the transcription factors signal transducer and activator of transcription 2 and IFN regulatory factor 9. Furthermore, it acts synergistically with IL-1β to induce beta cell apoptosis. Conclusions/interpretation The innate immune effects induced by IFNα may induce and amplify the adaptive immune response against human beta cells, indicating that IFNα has a central role in the early phases of diabetes.

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“…34 Previous reports showed that expression of lysosomal enzymes (MDH1, PC and ACLY) involved in glucose sensing tend to be different in human and rat b cells. 35 A proteome analysis focusing on glucose-responsive insulin production, which is a cellular physiological function specific to human pancreatic b cells, was also reported. The expression increased in Dicer 1 and SLC27A2 under high-glucose conditions.…”

Section: Discussionmentioning

confidence: 99%

A proteome analysis of pig pancreatic islets and exocrine tissue by liquid chromatography with tandem mass spectrometry

Nakashima

Miyagi-Shiohira

Kobayashi

et al. 2017

Islets

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Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is a proteome analysis method, and the shotgun analysis by LC-MS/MS comprehensively identifies proteins from tissues and cells with high resolving power. In this study, we analyzed the protein expression in pancreatic tissue by LC-MS/MS. Islets isolated from porcine pancreata (purity ≥95%) and exocrine tissue (purity ≥99%) were used in this study. LC-MS/MS showed that 13 proteins were expressed in pancreatic islets only (Group I), 43 proteins were expressed in both islets and exocrine tissue (Group I&E), and 102 proteins were expressed in exocrine tissue only (Group E). Proteins involved in islet differentiation and cell proliferation were identified in Group I (e.g. CLUS, CMGA, MIF). In addition, various functional proteins (e.g. SCG2, TBA1A) were identified in islet by using the new method of 'principal component analysis (PCA)'. However, the function of such proteins on islets remains unclear. EPCAM was identified in Group E. Group E was found to include proteins involved in clinical inflammatory diseases such as pancreatitis (e.g. CBPA1, CGL, CYTB, ISK1 and PA21B). Many of these identified proteins were reported less frequently in previous studies, and HS71B, NEC2, PRAF3 and SCG1 were newly detected in Group I while CPNS1, DPEP1, GANAB, GDIB, GGT1, HSPB1, ICTL, VILI, MUTA, NDKB, PTGR1, UCHL3, VAPB and VINC were newly detected in Group E. These results show that comprehensive expression analysis of proteins by LC-MS/MS is useful as a method to investigate new factors constructing cellular component, biological process, and molecular function.

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Species-Related Differences in the Proteome of Rat and Human Pancreatic Beta Cells

Cited by 15 publications

References 31 publications

Establishment of the First Well-differentiated Human Pancreatic Neuroendocrine Tumor Model

Establishment of the First Well-differentiated Human Pancreatic Neuroendocrine Tumor Model

Interferon-α mediates human beta cell HLA class I overexpression, endoplasmic reticulum stress and apoptosis, three hallmarks of early human type 1 diabetes

A proteome analysis of pig pancreatic islets and exocrine tissue by liquid chromatography with tandem mass spectrometry

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