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

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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.

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Figure 1. Figure 1. A schematic drawing of the pancreatic vasculature. Arterial blood flow form intralobular arteries are distributed through separate arterioles to the exocrine pancreas (90%‐95% of flow) or to the islets (5%‐10% of flow). Note that the islet blood flow is 5 to 10 times higher than that to the exocrine pancreas. The acini are drained through venules into intralobular veins, whereas the islets have a dual venous outflow. Some of the venous blood enters an insulo‐acinar portal system (IAP) where small venules communicate with exocrine capillaries. However, some venous blood from islets drains directly into the intralobular veins. This IAP is species dependent and its contribution to flow is unknown.
Figure 2. Figure 2. Possible sites for regulation of pancreatic blood flow. The islets and exocrine pancreas are supplied by different arterioles derived from the intralobular arteries. Around the arterioles are found smooth muscle cells (oval‐shaped yellow structures), which provide the major site for blood flow regulation. Note that some islet arterioles branch at the rim of the islets, whereas others penetrate into the core. In the latter case, the arterioles and their smooth muscle cells are exposed to islet hormones and metabolic mediators released from the endocrine cells. The venous drainage is either directly to intralobular veins; these vessels possess scarce smooth muscle cells, and presumably have no effect on pancreatic blood flow. The venules connecting islet capillaries to exocrine capillaries (the portal system) presumably lack smooth muscle cells, or they are very scarce.
Figure 3. Figure 3. The pancreatic circulation can be influenced by hormonal stimuli entering from the arterial circulation or by locally acting (paracrine) autacoids and hormones derived from intrapancreatic cells. Furthermore, release of neurotransmitters may also affects the gland. All these mechanisms may have a direct effect on vascular smooth muscle cells and also cause metabolic changes in parenchymal cells which can affect the circulation. There is also cross talk between the endocrine and tele‐acinar regions of the pancreas, but the exact role of this for blood floe regulation is unknown.
Figure 4. Figure 4. Experimental set‐up to study islet arteriolar vascular reactivity. In (A) a microdissected islet with a blood‐filled arteriole at the lower rim is seen. In (B) the perfusion pipette can be seen within the islet arteriole. For details of this, see the text and (). Islet diameter is 250 µm.
Figure 5. Figure 5. Schematic representation of purine metabolism in beta‐cells (top) and how this may affect P2X and P2Y receptors on endothelial cells and vascular smooth muscle cells. Increased beta‐cell metabolism leads to higher concentrations of ATP, ADP, and adenosine both intra‐ and extra‐cellularly. This may affect especially P2Y receptors on islet smooth muscle cells to achieve a metabolic vasodilation. Similar mechanisms are likely to be operative in the exocrine pancreas.


Figure 1. A schematic drawing of the pancreatic vasculature. Arterial blood flow form intralobular arteries are distributed through separate arterioles to the exocrine pancreas (90%‐95% of flow) or to the islets (5%‐10% of flow). Note that the islet blood flow is 5 to 10 times higher than that to the exocrine pancreas. The acini are drained through venules into intralobular veins, whereas the islets have a dual venous outflow. Some of the venous blood enters an insulo‐acinar portal system (IAP) where small venules communicate with exocrine capillaries. However, some venous blood from islets drains directly into the intralobular veins. This IAP is species dependent and its contribution to flow is unknown.


Figure 2. Possible sites for regulation of pancreatic blood flow. The islets and exocrine pancreas are supplied by different arterioles derived from the intralobular arteries. Around the arterioles are found smooth muscle cells (oval‐shaped yellow structures), which provide the major site for blood flow regulation. Note that some islet arterioles branch at the rim of the islets, whereas others penetrate into the core. In the latter case, the arterioles and their smooth muscle cells are exposed to islet hormones and metabolic mediators released from the endocrine cells. The venous drainage is either directly to intralobular veins; these vessels possess scarce smooth muscle cells, and presumably have no effect on pancreatic blood flow. The venules connecting islet capillaries to exocrine capillaries (the portal system) presumably lack smooth muscle cells, or they are very scarce.


Figure 3. The pancreatic circulation can be influenced by hormonal stimuli entering from the arterial circulation or by locally acting (paracrine) autacoids and hormones derived from intrapancreatic cells. Furthermore, release of neurotransmitters may also affects the gland. All these mechanisms may have a direct effect on vascular smooth muscle cells and also cause metabolic changes in parenchymal cells which can affect the circulation. There is also cross talk between the endocrine and tele‐acinar regions of the pancreas, but the exact role of this for blood floe regulation is unknown.


Figure 4. Experimental set‐up to study islet arteriolar vascular reactivity. In (A) a microdissected islet with a blood‐filled arteriole at the lower rim is seen. In (B) the perfusion pipette can be seen within the islet arteriole. For details of this, see the text and (). Islet diameter is 250 µm.


Figure 5. Schematic representation of purine metabolism in beta‐cells (top) and how this may affect P2X and P2Y receptors on endothelial cells and vascular smooth muscle cells. Increased beta‐cell metabolism leads to higher concentrations of ATP, ADP, and adenosine both intra‐ and extra‐cellularly. This may affect especially P2Y receptors on islet smooth muscle cells to achieve a metabolic vasodilation. Similar mechanisms are likely to be operative in the exocrine pancreas.

 

Teaching Material

L. Jansson, P.-O. Carlsson. Pancreatic Blood Flow with Special Emphasis on Blood Perfusion of the Islets of Langerhans. Compr Physiol 9: 2019, 799-837.

Didactic Synopsis

Major Teaching Points:

  • Pancreatic islets have a 5-10 fold higher basal and stimulated blood flow compared to exocrine pancreas.
  • These two blood flows are separately regulated.
  • The insulo-acinar portal system, where venules connect islet capillaries to acinar capillaries, provides an interface.
  • Both islets and acini have strong metabolic blood flow regulation, where adenosine and ATP/ADP play major roles.
  • Blood flow in both compartments is modified by local endothelial mediators, the nervous system and gastrointestinal hormones.
  • The responses to the nervous system are similar in endocrine and exocrine parts, whereas islets are more sensitive to endothelial mediators, especially nitric oxide.
  • Gastrointestinal hormones mainly influence the exocrine pancreatic blood flow, with the exception of incretin hormones and adipokines, which preferentially affect islet vasculature.
  • Changes in pancreatic circulation affect the development of type 2 diabetes mellitus and acute and chronic pancreatitis.

Didactic Legends

The figures—in a freely downloadable PowerPoint format—can be found on the Images tab along with the formal legends published in the article. The following legends to the same figures are written to be useful for teaching.

Figure 1 Teaching points: Schematic drawing of the vasculature in the pancreas, where the separate arteriolar contributions to the endocrine and exocrine parenchyma can be seen. Furthermore, the presence of an onsulo-acinar portal system connecting islet capillaries to those in the pancreas can be seen. The blood perfusion of the islets is 5-10 times higher than to the exocrine pancreas. This means that 5-10% of the whole pancreatic blood flow is diverted through the islets. No information on the blood flow though the insulo-acinar portal system is available.

Figure 2 Teaching points: Possible sites for regulation of pancreatic blood flow. Since islets and exocrine pancreas are supplied by different arterioles this means that their blood flows can be separately regulated. Some islet arterioles penetrate into the islets, and their smooth muscle cells can therefore be exposed to metabolically derived mediators from the islet cells as well as islet hormones. There is no evidence for capillary or venous regulation of blood flow.

Figure 3 Teaching points: The pancreatic circulation can be influenced by hormonal stimuli entering from the arterial circulation or by locally (paracrine) autacoids and hromoenes derived from cells within in the tissue. Release of neurotransmitters may also affect the gland. All these mechanisms mayhave a direct effect on vascular smooth muscle cells and also cause metabolic changes in parenchymal cells which can affect the circulation. There is also cross-talk between the endocrine andtele-acinar regions of the pancreas, but the exact role of this for blood floe regulation i sunknown.

Figure 4 Teaching points: Ann isolated islet is seen in (A) and the experimental set-up to study islet arteriolar vascular reactivity ex vivo is shown in (B). Islet diameter is 250 µm.

Figure 5 Teaching points: Purine metabolism in beta-cells (top) and how this may affect P2X- and P2Y-receptors on endothelial cells and vascular smooth muscle cells. Increased beta-cell metabolism leads to higher concentrations of ATP, ADP and adenosine both intra- and extra-cellularly, which affect purinoceptors.

 


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How to Cite

Leif Jansson, Per‐Ola Carlsson. Pancreatic Blood Flow with Special Emphasis on Blood Perfusion of the Islets of Langerhans. Compr Physiol 2019, 9: 799-837. doi: 10.1002/cphy.c160050