Oral glucose seems to exert a more pronounced effect on insulin secretion than does IV glucose, an effect which is typically explained by gut hormones acting on beta cells. But an alternate explanation might be that oral glucose would show up rapidly in the mesenteric venous blood, and if this were to perfuse pancreatic islets, gut hormones would not need to be implicated. Also, some islet capillaries seem to be anatomically designed to function with low blood pressure, as if they were on the receiving end of a portal circulation.
My question is specifically stimulated by the possibility that oral exposure to bisphenol A might lead to important physiologic effects (BPA is known to stimulate insulin secretion) even when blood concentrations of BPA are very low. This could happen if oral BPA could reach islet cells directly from the mesenteric vein, bypassing first pass metabolism in the liver.
This seems a little unlikely. While there is an intra-islet portal capillary circulation and a sequence of endocrine cell perfusion, this does not really involve mesenteric venous blood. Rather, arterial blood supply to the islets goes first to the core, which is beta-cell rich, then to the periphery of the islet, which is largely alpha and delta cells. From there, there is some flow to the acinar pancreas, but the venous flow from larger islets goes directly to portal venules and on to the portal circulation to the liver. If there is a BPA mediated effect, I would guess it is at the receptor level, and not due to circulatory anomalies.
This seems a little unlikely. While there is an intra-islet portal capillary circulation and a sequence of endocrine cell perfusion, this does not really involve mesenteric venous blood. Rather, arterial blood supply to the islets goes first to the core, which is beta-cell rich, then to the periphery of the islet, which is largely alpha and delta cells. From there, there is some flow to the acinar pancreas, but the venous flow from larger islets goes directly to portal venules and on to the portal circulation to the liver. If there is a BPA mediated effect, I would guess it is at the receptor level, and not due to circulatory anomalies.
Dear Dr. Olders,
I think your interesting question can be answered by doing an study as isolated pancreas perfusion ex vivo where you can procure pancreas together with duodenum and proximal jejunum and then pump perfuse the pancreas and instill an absorbable color agent in the duodenum and see if any of it will be seen in the pancreas sections.
Good luck with your intersting research idea.
No way. As stated by others, the arterial blood supply comes straight out from the splenic arteries to the islets and goes out to the exocrine pancreas. There are even no anomalies known with a mesenteric influx of blood towards the islets
Matthias is absolutely right. The pancreas receives arterial blood that will drain into the portal system.
Of course the blood to pancreas comes from splenic artery, but the question that has come to Dr. Olders mind also can be addressed by perfusion study.
The question might be more peculiar that it may seem from the first sight.
The islets inside the pancreas do receive the arterial blood indeed. However, there are both exocrine and endocrine pancreatic tissue islets in the liver parenchyma in app.10 per cent of the human population those receive blood likely from the sinusoids. Of course, one may speculate the Ellis's model of the hepatic circulation [H.Ellis. A re-examination of the structure of the mammalian liver. Am J Anat 1949; 85(3): 379-456] in another way, namely, that the terminal arterial branch in the classic hepatic lobul supplies the very islet, and not the hepatocytes.
On another hand, there is number of the pancreatic islets in some Actynopterygian fishes' liver; the fact that made several researchers to nominate that kind of liver structure as 'the hepatopancreas'. There is but little has been known as to its circulation pattern, hormonal production, and the portal blood oxygen level to the best of my knowledge.
Agreed with colleagues that the question warrents perfusion studies.
The following link contains a study discussing the possibility of treating diabetes through enhancement of blood supply to beta cells.
I know it may be far away from your question, but it still may help with some information.
Here is the link,
http://www.sciencedaily.com/releases/2013/05/130529154426.htm
As it is known that the blood to the pancreas comes from splenic artery to the islets and then it goes out the peripheral exocrine part of the pancreas and hence the possibilities of circulatory anomalies are ruled out. As stated by Dr. Steven Paraskevas the effect might be receptor mediated.
I think this is purely a theoretic question. There is no anatomic evidence supporting this notion. Blood flows from several arteries (not only the splenic one) to the pancreas parenchyma. Within the pancreas it develops a microcirculatory network which is not really known in humans but certainly it ends into veins that drain into the portal system. There, in regular condition, the pressure is very low and the blood is not supposed to invert its course to enter the pancreas. On the other hand, there is no anatomic evidence supporting a portal system within the pancreas developing from any supposedly afferent vein to the organ.
On a personal note I have to say that I am not really sure that in humans the microcirculation is as it is usually reported. Most studies have been carried out on rodents and, just to make an example, the concept of "the core of the islet", which is certainly evident in mice, cannot be transferred to humans as a whole since in humans the endocrine cell types are much more scattered within the islets.
As an afterthought, I would add the following consideration. Angiographists used to make selective nagiographies of the superior mesenteric artery. In the venous phase of the angiograms, if there was a portal venous system entering the pancreas from the mesenteric veins, you should see in the angiograms a delayed parenchymal phase of the pancreas following the opacification of the superior mesenteric vein. Which is not the case. This is a sort of in vivo perfusion experiment that has been made for years.
Andrey, do you have a reference for the existence in human livers of endocrine pancreatic islet tissue?
It seems to me a very important research to be done. It is possible possible a relationship in
between function and blood supply
For example, this one:
Terada T., Nakamura Y., Kakita A. Pathologic observations of intrahepatic peribiliary glands in 1,000 consecutive autopsy glands: Heterotopic pancreas in the liver. Gastroenterology 1990; 98: 1333-1337.
Thank you for the reference, Andrey. Unfortunately, it does not help: in their series of 1000 autopsies, they did not find any Langerhans' islet cells in livers.
However, the success of transplantation of isolated pancreatic islets into the liver using intraportal delivery suggests that these islets can function adequately when their entire blood supply is from the hepatic portal vein.
Henry, I am just a surgeon, and the stuff like the endocrine or exocrine islets is cloudy for me. It might be not accidently that endocrine pancreatic tissue cells receive the arterial blood, and the receptor cells for their hormonal control, hepatocytes, do the venous portal one as a counterbalanmce and a necessitate break in time. Moreover, in case of the (advanced only?) diabetes, the things may change and been altered so that the pancreatic fibrosis delays the venous blood outflow, and the diabetic liver fibrosis increases the arterial supply to this organ at the expense of that from the sinusoids. Actually, nobody knows precisely what the real hepatic microcirculation is, and how the arteriola and portal branches interact at which level. W. Ekataksin suggested that the hepatic artery supplies the biliary ducts and connectives tissue, but not the hepatocytes. It is logical, but has not proved for sure yet as far as I know.
On another hand, how is it possible that exocrine tissue of the pancreas can develop in the peribiliary tissue (which supplied by the arterial blood from the hepatic artery), and the endocrine one does not? What can prevent it from that?
What was important for me on the pancreas liver ectopy that how is it possible for the bile salts and pancreatic enzymes to coexist in the intrahepatic ducts without the enzymes activation and not causing the cholangitis that contradicts common opinion of the surgeons about the cholangitis or/and pancreatitis pathogenesis. It is both the enigma and a possible key for a refluxe cholangitis or refluxe pancreatitis prevention and treatment.
However, I thank you in my turn. I have learned that the islets are 'fed' on the oxygenised blood only, even being ectopic in the liver or wherever in the foregut.
So, this way or that, a perfusion model is needed to check your idea.
If you decide to do an ex vivo perfusion study, The model that we used earlier can be used, but with slight modification that you need to do, since you are intersted to see if there is any splanchnic venous blood going to islets, you should include a small portion of proximal jejunum too in your specimen. Here are the 2 ref. that may help you :
1. Diabetes Research 1992;19, 59-62
2. j. physiology 1981;318, 327-337
Hosein, I appreciate your providing the references, but the information you give, while very brief, creates much ambiguity in doing an online search. Could you possibly provide a DOI (if available) or the PubMed PMID? or even the principal author and title to help narrow down the search. Thank you very much!
Also, as a geriatric psychiatrist, I am unlikely to be doing a perfusion study any time soon! But perhaps others will take up the challenge!
Better late than never to ask, may a hepatic growth factor(s) inhibit an endocrine pathway of the pancreatoblasts differentiation, and can this contribute into the 2nd type diabetes development? Is anything known about the hepatocyte glycogen level and their proliferation rate in the DM?
miri, and Steen L. Jensen. Galanin inhibits tolbutamide-stimulated insulin secretion in the perfused pig pancreas, Diabetes Research (1992) 19, 59-62.
Holst, J.J., Lauritsen, K., Jensen, S. L., Nielsen, O. V., and Schaffilitzky de Muckadell. O. B. Secretion release from the isolated vascularly perfused pig duodenum. J. Physiology 1981, 318, 327-337
Good luck
Sorry, the first ref. did not print completely. It should be :
Bo Ahren, Hans Gregersen, Mohammad S.Amiri,
Rest of it is correct.
I came across a very early (1906) reference which suggests that the blood supply to the Islets of Langerhans which were studied was venous, without specifying the origin of the venous blood.
Dewitt LM. Morphology and physiology of areas of Langerhans in some vertebrates. The Journal of experimental medicine. 1906;8:193-239.
http://jem.rupress.org/content/8/2/193.full.pdf
There are old and new papers that convincingly demonstrate that the islets do NOT receive blood from the mesenterial (dvs portal) system:
Henderson et al., GUT 1981, 22: 158-167
Nyman et al., J Clin Invest 2008, 118: 3790-3797
This is evolutionary important: high insulin level support growht of the exocrine pancreas. Insulin is a growth factor!
Observe PubMed or Research Manager: I am preparing a paper to that end!
I still do not understand how this question still lingers. Let's try to see this reasoning hemodynamically. In order for the mesenteric vein blood to go to the pancreas you have two possibilities: 1) the entire pancreas is supplied by venous blood 2) the exocrine pancreas is supplied by the regular arterial blood and the endocrine by the venous blood. The first option is impossible as many arteries distribute within the pancreas and because in vivo arteriography demonstrate a parenchymal phase soon after the injection of the arteries and before the mesenteric vein becomes visible. Now option number two: apart from the fact that dissection studies never showed different veins coming from the exocrine pancreas and from the endocrine pancreas (and in this case we should say going to the endocrine pancreas), you should always consider that the blood moves from a region of higher pressure to a region with lower pressure. To fulfill this main issue you should postulate that within the pancreas you should have hundreds of thousands of small regions (islets) with low blood pressure embedded in a vast area where the pressure is higher. In other words each islet should be completely sealed from the blood circulating within the exocrine part. And this is simply not true as many corrosion casts studies have showed or even Bonner-Weir papers have demonstrated.
"I still do not understand how this question still lingers."
Human Psychology is an interesting thing; if a story seems reasonable, that can be enough to keep it alive even when the scientific facts do not provide any support. ;)
- Badges
- Science topic
- Similar topics
- Medicine
- Physiology