[PDF][PDF] Disruption of insulin receptor signaling in endothelial cells shows the central role of an intact islet blood flow for in vivo β-cell function

PO Carlsson, L Jansson - Diabetes, 2015 - researchgate.net
PO Carlsson, L Jansson
Diabetes, 2015researchgate.net
Worldwide there is massive increase in the prevalence of type 2 diabetes and the
International Diabetes Federation predicts that in 20 years some 600 million people
worldwide will be afflicted. In the US alone, the annual cost for diabetes care is an
astonishing $245 billion, of which 97% is targeted to type 2 diabetes. Hence, it is
immediately apparent that there is an urgent need to find new strategies capable of
preventing and treating this disease. Loss of pancreatic islet function is a central hallmark in …
Worldwide there is massive increase in the prevalence of type 2 diabetes and the International Diabetes Federation predicts that in 20 years some 600 million people worldwide will be afflicted. In the US alone, the annual cost for diabetes care is an astonishing $245 billion, of which 97% is targeted to type 2 diabetes. Hence, it is immediately apparent that there is an urgent need to find new strategies capable of preventing and treating this disease.
Loss of pancreatic islet function is a central hallmark in the progression of type 2 diabetes, and β-cell failure and dysfunction may even precede the advent of hyperglycemia. Most efforts to date have been put toward understanding the changes that occur in pancreatic islets in type 2 diabetes by in vitro studies of the endocrine cells, mainly the β-cells and the α-cells. However, what is often forgotten is that in the much more complex situation of in vivo these endocrine cells intercommunicate with the rest of the body by endocrine, neural, and paracrine signals. Endothelial cells in different organs substantially vary in their gene expression and thereby in their phenotype depending on signals from the surrounding parenchyma. In the islets of Langerhans, the endothelial cell phenotype differs from the rest of the pancreas by being exposed to vascular endothelial growth factor-A from the β-cells (1, 2). However, the endothelial cells also provide important factors to support β-cell function and differentiation, such as laminins and thrombospondin-1 (3, 4). Another aspect of the islet vascularity is the importance of this system for transport of oxygen and nutrients into the islets and transport of secreted hormones into the systemic vascular system. Islet blood perfusion is normally meticulously
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