Review
‘Giving and taking’: endothelial and β-cells in the islets of Langerhans

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The β-cells of the islets of Langerhans are embedded in a dense capillary network. The blood vessels supply the islet cells with nutrients and oxygen, and in turn take up the secreted islet hormones to deliver them to target tissues. In addition, vessels provide a basement membrane, which optimizes islet function. In this review we focus on the dynamic interactions between blood vessels and β-cells, which are pivotal for enhancing insulin expression and β-cell proliferation in response to increased insulin demand during body growth, pregnancy, and virtually all conditions associated with insulin resistance. Importantly, a failure in this adaptive response might contribute to the onset of type 2 diabetes mellitus.

Section snippets

Islet architecture

Research over the last decades has revealed a critical role of the islet of Langerhans and its glucose-sensing pancreatic β-cells for blood glucose control and onset of type 1 and type 2 diabetes mellitus (T2DM). The islet contains at least five endocrine cell types producing multiple hormones, including glucagon (α-cell), insulin (β-cell), pancreatic polypeptide (γ-cell), somatostatin (δ-cell) and ghrelin (ɛ-cell). The distribution of endocrine cells in the islet is species- dependent. For

Mutual signaling between islet endocrine cells and EC

Throughout development to adulthood, blood-borne signals and paracrine signals from EC are essential for induction of pancreatic development, endocrine cell differentiation and maintenance of islet function, especially insulin gene expression and glucose-stimulated insulin secretion (GSIS) in β-cells (Figure 2, Table 1).

Islet vasculature and its role in the onset of T2DM

T2DM results from the combination of insulin resistance in peripheral tissues and β-cell dysfunction, leading to a relative lack of insulin action. Interestingly, recent studies in animal models suggest that islet vascular dysfunction combined with islet inflammation plays a role in the onset of T2DM.

In the spontaneous type 2 diabetic non-obese Goto-Kakizaki (GK) rat, EC activation and oxidative stress were associated with insulin secretory defects 43, 44. It was proposed that activated EC or

Medical translation

EC are important for β-cell function and proliferation, so a better molecular understanding of how EC and β-cells interact with each other has potential for better understanding and treatment of type 1 and 2 diabetic patients.

For example, a promising therapeutic strategy for treatment of type 1 diabetic patients is to isolate islets from healthy donors and transplant them [49]. However, owing to the isolation process, these islets are disconnected from their supplying blood vessels and

Conclusion

It has become evident that the islet microvasculature is more than just a system to supply oxygen and nutrients, and also supports islet function on various molecular levels. Still, our molecular understanding of endothelial–endocrine interactions in the islet is limited. Many molecular players that fine-tune the optimal ratio of islet mass to vascularization still need to be investigated. However, several factors involved in islet vascularization are available for application in humans and

Acknowledgements

D.E., M.K. and E.L are supported by the German Research Foundation (DFG, LA1216/2-3) and the German Ministry for Research and Education (BMBF, AKROBAT). The authors apologize for not referring to some important papers fitting to the topic due to space constraints.

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