Pancreatic islet blood flow and its measurement

Jansson, Leif; Barbu, Andreea; Bodin, Birgitta; Drott, Carl Johan; Espes, Daniel; Gao, Xiang; Grapensparr, Liza; Källskog, Örjan; Lau, Joey; Liljebäck, Hanna; Palm, Fredrik; Quach, My; Sandberg, Monica; Strömberg, Victoria; Ullsten, Sara; Carlsson, Per‐Ola

doi:10.3109/03009734.2016.1164769

Cited by 130 publications

(116 citation statements)

References 152 publications

(225 reference statements)

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“…An increased islet perfusion in healthy individuals would facilitate insulin dispersal into the systemic circulation, but may not necessarily be linked to an increment in glucosedependent insulin secretion [10]. Accordingly, we did not observe any correlation between the increase in plasma insulin concentrations and perfusion after glucose administration in healthy individuals.…”

Section: Discussionmentioning

confidence: 47%

Pancreatic perfusion and subsequent response to glucose in healthy individuals and patients with type 1 diabetes

et al. 2016

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Aims/hypothesis The aim of this study was to investigate pancreatic perfusion and its response to a glucose load in patients with type 1 diabetes mellitus compared with non-diabetic ('healthy') individuals. Methods Eight individuals with longstanding type 1 diabetes and ten sex-, age-and BMI-matched healthy controls underwent dynamic positron emission tomography scanning with 15 O-labelled water before and after intravenous administration of glucose. Perfusion in the pancreas was measured. Portal and arterial hepatic perfusion were recorded as references. Results Under fasting conditions, total pancreatic perfusion was on average 23% lower in the individuals with diabetes compared with healthy individuals. Glucose increased total pancreatic and portal hepatic blood perfusion in healthy individuals by 48% and 38%, respectively. In individuals with diabetes there was no significant increase in either total pancreatic or portal hepatic perfusion.Conclusions/interpretation Individuals with type 1 diabetes have reduced basal pancreatic perfusion and a severely impaired pancreatic and splanchnic perfusion response to intravenous glucose stimulation.

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Section: Discussionmentioning

confidence: 47%

Pancreatic perfusion and subsequent response to glucose in healthy individuals and patients with type 1 diabetes

et al. 2016

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“…It has indeed been previously suggested that a prevented vasodilation may be protective for islet function during conditions with impaired glucose tolerance (Jansson et al. ).As expected, GIP had no effects on plasma glucose or serum insulin concentrations in normoglycemic animals (Holst and Gromada ). Neither did the ganglion blocker hexamethonium nor theophylline, an adenosine receptor antagonist in the used concentration (Carlsson et al.…”

Section: Discussionmentioning

confidence: 89%

“…This has been detailed elsewhere (Carlsson et al 2002a;Jansson et al 2016). A total of 3 9 10 5 black nonradioactive microspheres (EZ-Trac TM ; Triton Microspheres), with a diameter of 10 lm were injected via the catheter with its tip in the ascending aorta during 10 s whole simultaneously collecting an arterial reference sample (Carlsson et al 2002a).…”

Section: Blood Flow Measurements With Microspheresmentioning

confidence: 99%

Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats

et al. 2018

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The incretin hormone glucose‐dependent insulinotropic polypeptide (GIP) potentiates glucose‐stimulated insulin secretion, and affects β‐cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague–Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60 ng/kg*min) for 30 min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused ex vivo with GIP (10−6–10−12 mol/L) during normo‐ and hyperglycemia and arteriolar responsiveness was recorded. The highest dose of GIP potentiated insulin secretion during hyperglycemia, but had no effect in normoglycemic rats. The highest GIP concentration decreased blood perfusion of whole pancreas, pancreatic islets, duodenum, colon, liver and kidneys. The decrease in blood flow was unaffected by ganglion blockade or adenosine receptor inhibition. In contrast to this, in single perfused islets GIP induced a dose‐dependent arteriolar dilation. Thus, high doses of GIP exert a direct dilatory effect on islet arterioles in isolated islets, but induce a generalized vasoconstriction in splanchnic organs, including the whole pancreas and islets, in vivo. The latter effect is unlikely to be mediated by adenosine, the autonomic nervous system, or endothelial mediators.

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“…For example, the endocrine pancreas accounts for just approximately 2% of the total mass of the pancreas but receives ca. 15% of the total blood flow to the pancreas . In this study, whole pancreata were mechanically disrupted into small pieces.…”

Section: Resultsmentioning

confidence: 99%

A factorial design to identify process parameters affecting whole mechanically disrupted rat pancreata in a perfusion bioreactor

Sharp

Spitters

Vermette

2017

Biotechnology Progress

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Few studies report whole pancreatic tissue culture, as it is a difficult task using traditional culture methods. Here, a factorial design was used to investigate the singular and combinational effects of flow, dissolved oxygen concentration (D.O.) and pulsation on whole mechanically disrupted rat pancreata in a perfusion bioreactor. Whole rat pancreata were cultured for 72 h under defined bioreactor process conditions. Secreted insulin was measured and histological (haematoxylin and eosin (H&E)) as well as immunofluorescent insulin staining were performed and quantified. The combination of flow and D.O. had the most significant effect on secreted insulin at 5 h and 24 h. The D.O. had the biggest effect on tissue histological quality, and pulsation had the biggest effect on the number of insulin-positive structures. Based on the factorial design analysis, bioreactor conditions using high flow, low D.O., and pulsation were selected to further study glucose-stimulated insulin secretion. Here, mechanically disrupted rat pancreata were cultured for 24 h under these bioreactor conditions and were then challenged with high glucose concentration for 6 h and high glucose + IBMX (an insulin secretagogue) for a further 6 h. These cultures secreted insulin in response to high glucose concentration in the first 6 h, however stimulated-insulin secretion was markedly weaker in response to high glucose concentration + IBMX thereafter. After this bioreactor culture period, higher tissue metabolic activity was found compared to that of non-bioreacted static controls. More insulin- and glucagon-positive structures, and extensive intact endothelial structures were observed compared to non-bioreacted static cultures. H&E staining revealed more intact tissue compared to static cultures. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:432-444, 2018.

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Pancreatic islet blood flow and its measurement

Cited by 130 publications

References 152 publications

Pancreatic perfusion and subsequent response to glucose in healthy individuals and patients with type 1 diabetes

Pancreatic perfusion and subsequent response to glucose in healthy individuals and patients with type 1 diabetes

Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats

A factorial design to identify process parameters affecting whole mechanically disrupted rat pancreata in a perfusion bioreactor

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