Pancreatic Blood Flow with Special Emphasis on Blood Perfusion of the Islets of Langerhans

Abstract

The pancreatic islets are more richly vascularized than the exocrine pancreas, and possess a 5‐ to 10‐fold higher basal and stimulated blood flow, which is separately regulated. This is reflected in the vascular anatomy of the pancreas where islets have separate arterioles. There is also an insulo‐acinar portal system, where numerous venules connect each islet to the acinar capillaries. Both islets and acini possess strong metabolic regulation of their blood perfusion. Of particular importance, especially in the islets, is adenosine and ATP/ADP. Basal and stimulated blood flow is modified by local endothelial mediators, the nervous system as well as gastrointestinal hormones. Normally the responses to the nervous system, especially the parasympathetic and sympathetic nerves, are fairly similar in endocrine and exocrine parts. The islets seem to be more sensitive to the effects of endothelial mediators, especially nitric oxide, which is a permissive factor to maintain the high basal islet blood flow. The gastrointestinal hormones with pancreatic effects mainly influence the exocrine pancreatic blood flow, whereas islets are less affected. A notable exception is incretin hormones and adipokines, which preferentially affect islet vasculature. Islet hormones can influence both exocrine and endocrine blood vessels, and these complex effects are discussed. Secondary changes in pancreatic and islet blood flow occur during several conditions. To what extent changes in blood perfusion may affect the pathogenesis of pancreatic diseases is discussed. Both type 2 diabetes mellitus and acute pancreatitis are conditions where we think there is evidence that blood flow may contribute to disease manifestations. © 2019 American Physiological Society. Compr Physiol 9:799‐837, 2019.

Shielding islets with human amniotic epithelial cells enhances islet engraftment and revascularization in a murine diabetes model

“…Consequently, islets from several donors are needed to achieve engraftment of what is considered to be a marginal islet mass, ensuring adequate endocrine function, but sometimes also leading to β cell exhaustion in the long term . Major causes of early graft loss include the inflammatory reaction at the transplant site and the disruption of the islet microvasculature during the isolation process . Full revascularization of transplanted islets takes between 10 and 24 days .…”

Nutrient-Induced Metabolic Stress, Adaptation, Detoxification, and Toxicity in the Pancreatic β-Cell

“…Other terms like glucotoxicity, glucoadaptation, and glucolipotoxicity can still be used to describe some situations, particularly in the in vitro context, but they should be used only for what they mean and not more generally as they are currently. Although not covered here, there is a large variety of both intrinsic and extrinsic factors besides nutrients that influence the response to nutri-stress such as the plasticity in islet vasculature (115), the levels of various gluco-incretins like GLP-1 that may be protective for the b-cell (116), inflammatory cells that could favor toxicity or be beneficial depending on the context (117), or factors that are present in the serum from calorie-restricted animals (118). Finally, we need to learn more about the early defects or adaptive changes that occur in the natural history of the b-cell in diabetes to better distinguish causes from consequences of diabetes and have more studies with older animals since T2D largely occurs in aging individuals.…”

Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression

“…Adipokines preferentially affect islet vasculature [147]. Pancreatic hormones play a role in energy balance, exerting short-acting control, while insulin and leptin derived from adipose tissue are involved in long-acting adiposity signaling and regulate body weight [148].…”