The β-Cell/EC Axis: How Do Islet Cells Talk to Each Other?

Peiris, Heshan; Bonder, Claudine S.; Coates, P. Toby; Keating, Damien J.; Jessup, Claire F.

doi:10.2337/db13-0617

Cited by 91 publications

(120 citation statements)

References 83 publications

(75 reference statements)

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“…29 β-cell homeostasis and dysfunction Pancreatic β cells are biosensors that detect fluctuations in blood glucose levels and release appropriate amounts of insulin when required, thereby balancing self-preservation with regeneration. 30 Insulin-granule exocytosis occurs when extracellular levels of glucose increase and glucose enters β cells via glucose transporters 1 and 2 located on the cell surface ( Figure 2). 31 Intracellular glucose is quickly metabolized and increases the ATP:ADP ratio, which triggers closure of ATP-sensitive K + channels (K + ATP ) and cell depolarization ( Figure 2).…”

Section: Adenosine Systemmentioning

confidence: 99%

Adenosine signalling in diabetes mellitus—pathophysiology and therapeutic considerations

et al. 2015

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Adenosine is a key extracellular signalling molecule that regulates several aspects of tissue function by activating four G-protein-coupled receptors, A1, A2A, A2B and A1 adenosine receptors. Accumulating evidence highlights a critical role for the adenosine system in the regulation of glucose homeostasis and the pathophysiology of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Although adenosine signalling is known to affect insulin secretion, new data indicate that adenosine signalling also contributes to the regulation of β-cell homeostasis and activity by controlling the proliferation and regeneration of these cells as well as the survival of β cells in inflammatory microenvironments. Furthermore, adenosine is emerging as a major regulator of insulin responsiveness by controlling insulin signalling in adipose tissue, muscle and liver; adenosine also indirectly mediates effects on inflammatory and/or immune cells in these tissues. This Review critically discusses the role of the adenosine-adenosine receptor system in regulating both the onset and progression of T1DM and T2DM, and the potential of pharmacological manipulation of the adenosinergic system as an approach to manage T1DM, T2DM and their associated complications.

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Section: Adenosine Systemmentioning

confidence: 99%

Adenosine signalling in diabetes mellitus—pathophysiology and therapeutic considerations

et al. 2015

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“…Cultured islets may more faithfully reproduce in vivo conditions, but these multicellular clusters start to degenerate physically and biochemically when isolated and cultured ex vivo. For example, little is known about the ramifications for islet leukocyte survival and activation in the context of islet cultures, and critical cell-cell interactions are likely to be substantially disturbed by isolation and culture (Peiris et al 2014). Although cytokines are likely to contribute to progressive loss of b-cell function, some cytokines may have advantageous effects and could be involved in b-cell homeostasis, particularly early in the disease process.…”

Section: Cytokine-induced Stressmentioning

confidence: 99%

Oxidative and endoplasmic reticulum stress in β-cell dysfunction in diabetes

Hasnain¹,

Prins²,

McGuckin³

2015

Journal of Molecular Endocrinology

218

180

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The inability of pancreatic b-cells to make sufficient insulin to control blood sugar is a central feature of the aetiology of most forms of diabetes. In this review we focus on the deleterious effects of oxidative stress and endoplasmic reticulum (ER) stress on b-cell insulin biosynthesis and secretion and on inflammatory signalling and apoptosis with a particular emphasis on type 2 diabetes (T2D). We argue that oxidative stress and ER stress are closely entwined phenomena fundamentally involved in b-cell dysfunction by direct effects on insulin biosynthesis and due to consequences of the ER stress-induced unfolded protein response. We summarise evidence that, although these phenomenon can be driven by intrinsic b-cell defects in rare forms of diabetes, in T2D b-cell stress is driven by a range of local environmental factors including increased drivers of insulin biosynthesis, glucolipotoxicity and inflammatory cytokines. We describe our recent findings that a range of inflammatory cytokines contribute to b-cell stress in diabetes and our discovery that interleukin 22 protects b-cells from oxidative stress regardless of the environmental triggers and can correct much of diabetes pathophysiology in animal models. Finally we summarise evidence that b-cell dysfunction is reversible in T2D and discuss therapeutic opportunities for relieving oxidative and ER stress and restoring glycaemic control.

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“…Insulin receptor can be detected on endothelial cells [79]. It is can activate PI-3 kinase which regulate the expression of eNOS gene in endothelial cells, promoting intra-islet blood flow and modulates vascular tone [67,80]. When suffering diabetes, the inhibition of PI-3 kinase activity may lead to endothelial dysfunctions [80].…”

Section: Resultsmentioning

confidence: 99%

“…If VEGFR is blocked by antagonists, such as AG-013736, a small-molecule VEGFR tyrosine kinase inhibitor, the density of capillaries is significantly reduced [66]. In islets, β cells secrete large amounts of VEGF-A early in development and throughout adult life [67], and it's controlled by pancreatic and duodenal homeobox 1 (Pdx1) promoter [57].…”

Section: The Endocrine Role Of β Cells To Islet Endothelial Cellsmentioning

confidence: 99%

The endocrine role between β cells and intra-islet endothelial cells [Review]

Cao

Wang

2014

Endocr J

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Abstract. The islets of Langerhans is the endocrine function region of pancreas, which exist in five cell types. The majority of endocrine cells are insulin-secreting β cells, mixed up with glucagon-secreting α-cells. The islets of Langerhans are highly vascularized, and the capillary network around the islet is about five times denser than that in the exocrine tissues. It guarantees endocrine cells adequately contact with the capillary networks. Above mentioned is the basis of deep study the interaction between β cells and capillary. Increasing number of studies contribute to the consensus that endothelial cells have positive effects in the islet microenvironment. Endothelial cells can act as endocrine cells which release many active substances, such as hepatocyte growth factors (HGF), thrombospondin-1(TSP-1), laminins, and collagens by means of different molecule pathways, inducing β cells differentiation, proliferation, survivor, and insulin release next to the vessels. Apart from the effect of endothelial cells on β cells by paracrine fashion, the islets can utilize VEGF-A, angiopoietin-1 and insulin signaling to increase the interaction with endothelial cells. As the endocrine role of endothelial cells to β cells, it may be a novel target to stimulate β cells regeneration, promote vascularization post islet transplantation strategy in the treatment of diabetes mellitus.

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The β-Cell/EC Axis: How Do Islet Cells Talk to Each Other?

Cited by 91 publications

References 83 publications

Adenosine signalling in diabetes mellitus—pathophysiology and therapeutic considerations

Adenosine signalling in diabetes mellitus—pathophysiology and therapeutic considerations

Oxidative and endoplasmic reticulum stress in β-cell dysfunction in diabetes

The endocrine role between β cells and intra-islet endothelial cells [Review]

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