Microvasculature of the Pancreatic Islets of Langerhans in Health and Diabetes.

Abstract

Insulin and glucagon secreted by beta- and alpha-cells of the islets of Langerhans, respectively, regulate tissue glucose uptake, metabolism, and glycolysis. Islets represent around 2% of pancreatic mass but receive around 20% of the arterial blood flow; arteriolar blood entering the islet giving rise to a dense, fenestrated capillary bed enabling rapid glucose sensing and prompt hormone excretion. Local regulation of blood flow within each islet is achieved by contractile pericytes lining the capillaries. Endothelial cells and pericytes contribute to the lineage commitment and maturation of islet endocrine cells in utero, which can be disrupted by maternal under- or over-nutrition. Vascular cells generate the basement membranes juxtaposing endocrine cells and ensure optimal endocrine function. In type 2 diabetes, the intra-islet capillary density is increased but capillary walls are thickened with loss of fenestration and dysregulated hormone release. De-differentiation of pericytes to myofibroblasts causes islet fibrosis. In type 1 diabetes, this pathology is exacerbated by inflammatory cell-derived cytokine action on vascular cells. Pancreatic cancer-associated diabetes (type 3c), as seen with ductal adenocarcinoma, involves fibrotic thickening of the peri-islet basement membrane caused by tumor-derived growth factors. Conversely, insulin secretion may contribute to cancer growth. Therapeutic options to prevent or delay diabetes include maintaining islet vascular function through limiting cellular oxidative stress and inflammation.