Heterogeneity of the Human Pancreatic Islet

Dybala, Michael P.; Hara, Manami

doi:10.2337/db19-0072

Cited by 82 publications

(74 citation statements)

References 34 publications

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“…Rodent islets have a mantle-core structure, in that non-β-cells are mostly found in the periphery while β-cells are in the center of the islet [175,176]. Human islets, however, were shown to be very heterogenous with respect to size, cell composition and islet architecture, and they do not have the mantle-like organization reported in rodents [173]. Pancreatic islets are highly vascularized; the islet capillary network is approximately five times denser in islets than in the exocrine pancreas [177].…”

Section: Insulin and The Islet Microenvironmentmentioning

confidence: 99%

“…β-cells reside in a complex islet microenvironment where they interact with other endocrine cells, such as glucagon-secreting β-cells, somatostatin-secreting β-cells, pancreatic polypeptide-secreting PP cells, ghrelin-secreting ε-cells, and with vascular endothelial cells, as well as neuronal projections. Differences in islet architecture between rodents and humans have been reported [173,174]. Rodent islets have a mantle-core structure, in that non-β-cells are mostly found in the periphery while β-cells are in the center of the islet [175,176].…”

Section: Insulin and The Islet Microenvironmentmentioning

confidence: 99%

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Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus

Rachdaoui

2020

IJMS

158

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Insulin, a hormone produced by pancreatic β-cells, has a primary function of maintaining glucose homeostasis. Deficiencies in β-cell insulin secretion result in the development of type 1 and type 2 diabetes, metabolic disorders characterized by high levels of blood glucose. Type 2 diabetes mellitus (T2DM) is characterized by the presence of peripheral insulin resistance in tissues such as skeletal muscle, adipose tissue and liver and develops when β-cells fail to compensate for the peripheral insulin resistance. Insulin resistance triggers a rise in insulin demand and leads to β-cell compensation by increasing both β-cell mass and insulin secretion and leads to the development of hyperinsulinemia. In a vicious cycle, hyperinsulinemia exacerbates the metabolic dysregulations that lead to β-cell failure and the development of T2DM. Insulin and IGF-1 signaling pathways play critical roles in maintaining the differentiated phenotype of β-cells. The autocrine actions of secreted insulin on β-cells is still controversial; work by us and others has shown positive and negative actions by insulin on β-cells. We discuss findings that support the concept of an autocrine action of secreted insulin on β-cells. The hypothesis of whether, during the development of T2DM, secreted insulin initially acts as a friend and contributes to β-cell compensation and then, at a later stage, becomes a foe and contributes to β-cell decompensation will be discussed.

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Section: Insulin and The Islet Microenvironmentmentioning

confidence: 99%

Section: Insulin and The Islet Microenvironmentmentioning

confidence: 99%

Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus

Rachdaoui

2020

IJMS

158

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“…However, these techniques demonstrate a high heterogeneity in term of PIs sizes and morphology. Isolated human islets are not uniform in size, usually ranging 50–500 µm in diameter [64]. Larger islets are more prone to develop core necrosis after transplantation, until revascularization occurs [65].…”

Section: Pseudo‐islet: the Pancreatic Endocrine Organoidmentioning

confidence: 99%

Generation of insulin‐secreting organoids: a step toward engineering and transplanting the bioartificial pancreas

et al. 2020

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Summary Diabetes is a major health issue of increasing prevalence. ß‐cell replacement, by pancreas or islet transplantation, is the only long‐term curative option for patients with insulin‐dependent diabetes. Despite good functional results, pancreas transplantation remains a major surgery with potentially severe complications. Islet transplantation is a minimally invasive alternative that can widen the indications in view of its lower morbidity. However, the islet isolation procedure disrupts their vasculature and connection to the surrounding extracellular matrix, exposing them to ischemia and anoikis. Implanted islets are also the target of innate and adaptive immune attacks, thus preventing robust engraftment and prolonged full function. Generation of organoids, defined as functional 3D structures assembled with cell types from different sources, is a strategy increasingly used in regenerative medicine for tissue replacement or repair, in a variety of inflammatory or degenerative disorders. Applied to ß‐cell replacement, it offers the possibility to control the size and composition of islet‐like structures (pseudo‐islets), and to include cells with anti‐inflammatory or immunomodulatory properties. In this review, we will present approaches to generate islet cell organoids and discuss how these strategies can be applied to the generation of a bioartificial pancreas for the treatment of type 1 diabetes.

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“…The ultimate challenge to test such a hypothesis lies in the ability to resolve the identities of individual cells and to simultaneously monitor their activity in live islets. In addition, because the spatial organizations of α and β cells are highly heterogeneous from islet to islet 33,34 , quantitatively comparing Ca 2+ oscillations in different islets is difficult. To address this problem, we have developed a microfluidic device attached to the spinning-disc confocal microscope, which allows individual cells to be imaged under physiological conditions for up to ~2 hrs.…”

Section: Introductionmentioning

confidence: 99%

Pancreatic α and β cells are globally phase-locked

Ren

Han

et al. 2020

Preprint

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The Ca2+ modulated pulsatile secretions of glucagon and insulin by pancreatic α and β cells play a key role in glucose metabolism and homeostasis. However, how different types of islet cells couple and coordinate via paracrine interactions to produce various Ca2+ oscillation patterns are still elusive. By designing a microfluidic device to facilitate long-term recording of islet Ca2+ activity at single cell level and simultaneously identifying different cell types in live islet imaging, we show heterogeneous but intrinsic Ca2+ oscillation patterns of islets upon glucose stimulation. The α and β cells oscillate in antiphase and are globally phase locked to various phase delays, causing fast, slow or mixed oscillations. A mathematical model of coupled phase oscillators quantitatively agrees with experiments and reveals the essential role of paracrine regulations in tuning the oscillation modes. Our study highlights the importance of cell-cell interactions to generate stable but tunable islet oscillation patterns.

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Heterogeneity of the Human Pancreatic Islet

Cited by 82 publications

References 34 publications

Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus

Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus

Generation of insulin‐secreting organoids: a step toward engineering and transplanting the bioartificial pancreas

Pancreatic α and β cells are globally phase-locked

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