The supply chain of human pancreatic β cell lines

Scharfmann, Raphaël; Staels, Willem; Albagli, Olivier

doi:10.1172/jci129484

Cited by 43 publications

(35 citation statements)

References 144 publications

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“…The central principle of glucose homeostasis is that pancreatic beta cells secrete insulin in response to glucose, and insulin acts upon target tissues, such as the liver, muscle, and adipose tissue, to reduce blood glucose levels. However, in addition to glucose, beta cells respond to a vast array of metabolic and endocrine signals, including lipids, hormones, and cytokines ( Scharfmann et al., 2019 ). Therefore, beta cells integrate a plethora of systemic signals that reflect the metabolic status and secrete appropriate amounts of insulin to maintain metabolic homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion

Drareni

Ballaire²,

Alzaïd

et al. 2020

Cell Reports

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Summary Glucose homeostasis is maintained through organ crosstalk that regulates secretion of insulin to keep blood glucose levels within a physiological range. In type 2 diabetes, this coordinated response is altered, leading to a deregulation of beta cell function and inadequate insulin secretion. Reprogramming of white adipose tissue has a central role in this deregulation, but the critical regulatory components remain unclear. Here, we demonstrate that expression of the transcriptional coregulator GPS2 in white adipose tissue is correlated with insulin secretion rate in humans. The causality of this relationship is confirmed using adipocyte-specific GPS2 knockout mice, in which inappropriate secretion of insulin promotes glucose intolerance. This phenotype is driven by adipose-tissue-secreted factors, which cause increased pancreatic islet inflammation and impaired beta cell function. Thus, our study suggests that, in mice and in humans, GPS2 controls the reprogramming of white adipocytes to influence pancreatic islet function and insulin secretion.

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Section: Introductionmentioning

confidence: 99%

Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion

Drareni

Ballaire²,

Alzaïd

et al. 2020

Cell Reports

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“…Next, it is also shown in [24] that the translation rate ranges between 1 and 1000 proteins per mRNA per hour. This allows us to set k and α to plausible values between 1 and 1000 h −1 multiplied by the number of implanted cells N which is taken to be 1 billion — equal to the number of β -cells in the human pancreas [50]. The sequestration rate η is chosen to be large enough to reflect a fast sense/antisense RNA hybridization.…”

Section: Antithetic Proportional-integral Control Of Plasma Glucosementioning

confidence: 99%

Genetically Engineered Proportional-Integral Feedback Controllers for Robust Perfect Adaptation in Mammalian Cells

Frei¹,

Chang²,

Filo³

et al. 2020

Preprint

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Mammalian cells collectively maintain a consistent internal milieu that supports their host’s survival in varying and uncertain environments. This homeostasis is often achieved through negative feedback loops that act at various levels of biological organization, from the system and organ levels down to gene expression at the molecular scale. Recently, a molecular regulatory motif has been discovered that enables a regulated variable to adapt perfectly (at the steady state) to network and parameter changes and to persistent environmental perturbations. The regulatory motif that achieves this robust perfect adaptation property realizes integral feedback, a control strategy that employs mathematical integration in a negative feedback loop. Here, we present the first synthetic implementation of integral feedback in mammalian cells. We show that this implementation successfully maintains constant levels of a transcription factor, even when its degradation is significantly increased. Furthermore, we establish the structural robustness properties of our controlled system by demonstrating that perturbing the network topology does not affect the transcription factor levels. We believe that the ability to robustly and predictably regulate the expression levels of genes will both become an indispensable tool for basic research as well as lead to substantial advances in the development of industrial biotechnology and cell-based therapies.

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“…Early research in T1D was originally based on limited human pancreatic specimens (Foulis and Stewart, 1984;Foulis et al, 1986), experimental mouse models [mainly the non-obese diabetic (NOD) mouse (Anderson and Bluestone, 2005)], or on beta cell lines (Scharfmann et al, 2019). During the last decades, the scientific community realized the importance of systematic organ collection and distribution for research and founded several biobanks, such as the Exeter Archival Diabetes Biobank (EADB) (Foulis et al, 1986), the Dutch Pancreas Biobank (Strijker et al, 2018), and the IMIDIA Biobank (Solimena et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Whole-Slide Image Analysis of Human Pancreas Samples to Elucidate the Immunopathogenesis of Type 1 Diabetes Using the QuPath Software

Apaolaza

Πετροπούλου

Rodríguez-Calvo

2021

Front. Mol. Biosci.

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Type 1 diabetes is a chronic disease of the pancreas characterized by the loss of insulin-producing beta cells. Access to human pancreas samples for research purposes has been historically limited, restricting pathological analyses to animal models. However, intrinsic differences between animals and humans have made clinical translation very challenging. Recently, human pancreas samples have become available through several biobanks worldwide, and this has opened numerous opportunities for scientific discovery. In addition, the use of new imaging technologies has unraveled many mysteries of the human pancreas not merely in the presence of disease, but also in physiological conditions. Nowadays, multiplex immunofluorescence protocols as well as sophisticated image analysis tools can be employed. Here, we described the use of QuPath—an open-source platform for image analysis—for the investigation of human pancreas samples. We demonstrate that QuPath can be adequately used to analyze whole-slide images with the aim of identifying the islets of Langerhans and define their cellular composition as well as other basic morphological characteristics. In addition, we show that QuPath can identify immune cell populations in the exocrine tissue and islets of Langerhans, accurately localizing and quantifying immune infiltrates in the pancreas. Therefore, we present a tool and analysis pipeline that allows for the accurate characterization of the human pancreas, enabling the study of the anatomical and physiological changes underlying pancreatic diseases such as type 1 diabetes. The standardization and implementation of these analysis tools is of critical importance to understand disease pathogenesis, and may be informative for the design of new therapies aimed at preserving beta cell function and halting the inflammation caused by the immune attack.

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The supply chain of human pancreatic β cell lines

Cited by 43 publications

References 144 publications

Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion

Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion

Genetically Engineered Proportional-Integral Feedback Controllers for Robust Perfect Adaptation in Mammalian Cells

Whole-Slide Image Analysis of Human Pancreas Samples to Elucidate the Immunopathogenesis of Type 1 Diabetes Using the QuPath Software

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