Intercellular Communication in the Islet of Langerhans in Health and Disease

Ng, Xue Wen; Chung, Yong Hee; Piston, David W.

doi:10.1002/cphy.c200026

Cited by 23 publications

(24 citation statements)

References 448 publications

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“…To sum up, the recent theoretical works have partly confirmed some of the recent experimental findings and thereby contributed to our understanding of the complex signaling mechanisms within the islets. However, there is still a long road to drive before we will fully understand how functionally heterogeneous beta cell populations interact among each other, with other cells, and with the dynamical environment by means which may involve paracrine and other modes of intra-islet signaling ( 214 – 216 ), the effect of incretins ( 217 ), as well as long feedback loops, for instance between the liver and the pancreas ( 137 ). We firmly believe that the tools developed in the field of computational physiology and network science will help us to address these issues and will provide us further insights into functional properties, as well as the underlying mechanisms that guide the multicellular dynamics of endocrine cells.…”

Section: Functional Implications Of Beta Cell Network Analysismentioning

confidence: 99%

“…Fourth, the pancreatic islets are multicellular micro-organs that comprise predominantly alpha, beta, delta cells and communication among them is essential for proper function ( 73 , 214 , 251 , 252 ). While direct electrical coupling through gap-junctions is the key determinant ensuring synchronous beta cell activity ( 76 , 77 ) and was also found to be present between beta and delta cells ( 253 , 254 ), islet cells also communicate by paracrine, autocrine, and other juxtacrine signaling pathways ( 73 , 215 , 252 ).…”

Section: Frontiers Of Islet Network Science: Assessing Multicellular ...mentioning

confidence: 99%

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From Isles of Königsberg to Islets of Langerhans: Examining the Function of the Endocrine Pancreas Through Network Science

Stožer

Šterk²,

Leitgeb³

et al. 2022

Front. Endocrinol.

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Islets of Langerhans are multicellular microorgans located in the pancreas that play a central role in whole-body energy homeostasis. Through secretion of insulin and other hormones they regulate postprandial storage and interprandial usage of energy-rich nutrients. In these clusters of hormone-secreting endocrine cells, intricate cell-cell communication is essential for proper function. Electrical coupling between the insulin-secreting beta cells through gap junctions composed of connexin36 is particularly important, as it provides the required, most important, basis for coordinated responses of the beta cell population. The increasing evidence that gap-junctional communication and its modulation are vital to well-regulated secretion of insulin has stimulated immense interest in how subpopulations of heterogeneous beta cells are functionally arranged throughout the islets and how they mediate intercellular signals. In the last decade, several novel techniques have been proposed to assess cooperation between cells in islets, including the prosperous combination of multicellular imaging and network science. In the present contribution, we review recent advances related to the application of complex network approaches to uncover the functional connectivity patterns among cells within the islets. We first provide an accessible introduction to the basic principles of network theory, enumerating the measures characterizing the intercellular interactions and quantifying the functional integration and segregation of a multicellular system. Then we describe methodological approaches to construct functional beta cell networks, point out possible pitfalls, and specify the functional implications of beta cell network examinations. We continue by highlighting the recent findings obtained through advanced multicellular imaging techniques supported by network-based analyses, giving special emphasis to the current developments in both mouse and human islets, as well as outlining challenges offered by the multilayer network formalism in exploring the collective activity of islet cell populations. Finally, we emphasize that the combination of these imaging techniques and network-based analyses does not only represent an innovative concept that can be used to describe and interpret the physiology of islets, but also provides fertile ground for delineating normal from pathological function and for quantifying the changes in islet communication networks associated with the development of diabetes mellitus.

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Section: Functional Implications Of Beta Cell Network Analysismentioning

confidence: 99%

Section: Frontiers Of Islet Network Science: Assessing Multicellular ...mentioning

confidence: 99%

From Isles of Königsberg to Islets of Langerhans: Examining the Function of the Endocrine Pancreas Through Network Science

Stožer

Šterk²,

Leitgeb³

et al. 2022

Front. Endocrinol.

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“…Pancreatic islets and MIN6-pseudoislets are particularly suited to illustrating the advantages of measuring the reactions of 3D cellular aggregates, as compared with single cells. The different cell types of the pancreatic islet interact, and the secretion pattern of the alpha cells is subject to paracrine inhibition by beta- and delta-cells [ 12 , 16 ]. Even the comparatively homogeneous MIN6 pseudoislet cells illustrate this point since MIN6-cells within pseudoislets respond more strongly to metabolic stimulation than single MIN6- cells [ 11 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…The pancreatic islet is a naturally occurring miniorgan of spheroidal shape once it has been isolated from the surrounding exocrine pancreatic tissue. Pancreatic islets contain multiple cell types, most notably the beta-cells that synthesize and release insulin, the main glucoregulatory hormone of the human body [ 12 ]. The research on pancreatic islets is of major importance to the development of more effective treatments for diabetes mellitus, a chronic metabolic disease that causes hardship and suffering on a worldwide scale [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

An Immersible Microgripper for Pancreatic Islet and Organoid Research

et al. 2022

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To improve the predictive value of in vitro experimentation, the use of 3D cell culture models, or organoids, is becoming increasingly popular. However, the current equipment of life science laboratories has been developed to deal with cell monolayers or cell suspensions. To handle 3D cell aggregates and organoids in a well-controlled manner, without causing structural damage or disturbing the function of interest, new instrumentation is needed. In particular, the precise and stable positioning in a cell bath with flow rates sufficient to characterize the kinetic responses to physiological or pharmacological stimuli can be a demanding task. Here, we present data that demonstrate that microgrippers are well suited to this task. The current version is able to work in aqueous solutions and was shown to position isolated pancreatic islets and 3D aggregates of insulin-secreting MIN6-cells. A stable hold required a gripping force of less than 30 mN and did not affect the cellular integrity. It was maintained even with high flow rates of the bath perfusion, and it was precise enough to permit the simultaneous microfluorimetric measurements and membrane potential measurements of the single cells within the islet through the use of patch-clamp electrodes.

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“…The regulation of islet β-cells by their cilia goes beyond cell-autonomous processes such as GSIS, as cilia also mediate β/δ-cell paracrine crosstalk and potentially bidirectional signaling via Eph-ephrins and cell-cell contact ( 17 , 18 ). As the islet field moves toward an integrated understanding of cellular connectivity and continues to build on tri-partite hormone regulation models ( 75 ), studies on islet cell cilia should aim to elucidate both cell-intrinsic ciliary pathways regulating glucose-stimulated hormone secretion, as well as cilia-mediated juxtacrine and paracrine signaling among different cell types. Therefore, we propose several obvious “next-step” lines of investigation for studying cilia function in islets.…”

Section: Open Questions In Islet Cilia Researchmentioning

confidence: 99%

Cilia Action in Islets: Lessons From Mouse Models

Cho

Hughes²

2022

Front. Endocrinol.

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Primary cilia as a signaling organelle have garnered recent attention as a regulator of pancreatic islet function. These rod-like sensors exist on all major islet endocrine cell types and transduce a variety of external cues, while dysregulation of cilia function contributes to the development of diabetes. The complex role of islet primary cilia has been examined using genetic deletion targeting various components of cilia. In this review, we summarize experimental models for the study of islet cilia and current understanding of mechanisms of cilia regulation of islet hormone secretion. Consensus from these studies shows that pancreatic cilia perturbation can cause both endocrine and exocrine defects that are relevant to human disease. We discuss future research directions that would further elucidate cilia action in distinct groups of islet cells, including paracrine and juxtacrine regulation, GPCR signaling, and endocrine-exocrine crosstalk.

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Intercellular Communication in the Islet of Langerhans in Health and Disease

Cited by 23 publications

References 448 publications

From Isles of Königsberg to Islets of Langerhans: Examining the Function of the Endocrine Pancreas Through Network Science

From Isles of Königsberg to Islets of Langerhans: Examining the Function of the Endocrine Pancreas Through Network Science

An Immersible Microgripper for Pancreatic Islet and Organoid Research

Cilia Action in Islets: Lessons From Mouse Models

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