Glucose-induced islet blood flow increase in rats: interaction between nervous and metabolic mediators

Carlsson, Per‐Ola; Olsson, Richard F.; Källskog, Örjan; Bodin, Birgitta; Andersson, Arne; Jansson, Leif

doi:10.1152/ajpendo.00044.2002

Cited by 57 publications

(70 citation statements)

References 49 publications

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“…The assessment was done by an injection of marked microspheres with rapid (10 s) killing of the animals following injection [13]. Thus the results described in those studies may not represent dynamic change in flow as assessed in the current study.…”

Section: Discussionmentioning

confidence: 88%

Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging

et al. 2009

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Aims/hypothesis Loss of pancreatic beta cell mass and function leads to the development of diabetes mellitus. Currently there is no technical way to non-invasively image islet function and mass. Murine models suggest that islets are highly vascularised organs that make a significant contribution to the total pancreatic blood flow. The current study was undertaken to test with arterial spin labelling (ASL) magnetic resonance imaging if islet mass and/or stimulation of human pancreatic islets by hyperglycaemia can differentially increase whole-pancreas perfusion, thereby distinguishing non-diabetic from type 1 diabetic patients. Methods We assessed pancreatic blood flow using ASL at baseline, during a hyperglycaemia clamp study (glucose at 11 mmol/l) and during recovery to euglycaemia. Results Seventeen healthy volunteers and seven type 1 diabetic patients were studied. In healthy volunteers we observed no change in pancreatic blood flow during the three phases of the study. A trend for an increase in blood flow was observed in the two control tissues, the liver and kidney. Similarly, there was no significant difference in blood flow during the three stages (baseline, hyperglycaemia and recovery) in diabetic patients and there was no significant difference observed between diabetic patients and normal volunteers. Conclusions/interpretation Our data suggest that in humans neither increased demand nor islet mass has a substantial influence on pancreatic perfusion. It is possible, however, that the current state-of-the art imaging technology employed in this study might not be sensitive enough to distinguish between a true effect and noise.Trial registration: ClinicalTrials.gov NCT00280085 Funding: This study was fully funded by a grant from Pfizer.

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Section: Discussionmentioning

confidence: 88%

Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging

et al. 2009

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“…The physiological and/or metabolic events underlying the increase in islet blood flow under these circumstances are unknown. However, we believe that it could reflect an increased metabolism of the islets, since we have recently shown that this can lead to a pronounced increase in islet blood flow in other models, in which the major mediator of the response seems to be adenosine (Carlsson et al 2002). It can also be speculated that growth factors involved in the regeneration of islets (see Nielsen et al 1999) can influence islet blood flow, but this notion remains hypothetical.…”

Section: Discussionmentioning

confidence: 91%

Lack of compensatory increase in islet blood flow and islet mass in GK rats following 60% partial pancreatectomy

Svensson

Östenson²,

Bodin³

et al. 2005

Journal of Endocrinology

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The effects of a 60% partial pancreatectomy were studied in hyperglycemic GK (Goto-Kakizaki) rats. Partial pancreatectomy or a sham operation was performed on 12-weekold female Wistar rats, GK rats or hybrids between male GK rats and female Wistar rats. Measurements of pancreatic blood flow and islet blood flow were performed by a microsphere technique 2 weeks after surgery. Glucose tolerance was decreased in hybrid compared with Wistar rats, and in GK rats compared with both hybrid and Wistar rats before surgery. Partial pancreatectomy induced minor changes in glucose tolerance. Wistar rats had a decreased islet mass following partial pancreatectomy. Both hybrid and GK rats showed a significant decrease in relative islet volume, but only GK rats in total islet mass, compared with Wistar rats 2 weeks after surgery. Pancreatic blood flow and islet blood flow did not significantly differ between sham-operated Wistar, hybrid or GK rats. After partial pancreatectomy, islet blood flow in relation to islet mass increased 3-fold in Wistar rats and 2-fold in hybrid rats. In contrast, GK rats showed no increase in islet blood flow following partial pancreatectomy. It is concluded that compensatory mechanisms after partial pancreatectomy are operating less efficiently in hybrid and GK rats.

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“…Islet blood perfusion is normally tightly regulated at the arteriolar level by nervous, endocrine and metabolic mechanisms [12,13]. A dose-and time-dependent preferential increase in blood flow is induced by glucose [13,14].…”

Section: Introductionmentioning

confidence: 99%

Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

et al. 2012

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Aims/hypothesis The blood perfusion of individual pancreatic islets is highly variable, with a subgroup of islets having high perfusion and blood vessels responsive to further blood flow increase induced by glucose. This study tested the hypothesis that there is heterogeneity between islets with regard to beta cell proliferation, function and gene expression based on differences in their blood perfusion. Methods Fluorescent microspheres were injected into the ascending aorta, and then microsphere-containing and nonmicrosphere-containing pancreatic islets were isolated for investigation. By this procedure, the 5% of islets with the greatest blood perfusion were identified for study. Islet endothelial cells were isolated separately to investigate the role of improved vascular support in the observed differences. Results The vascular network was found to be more dense and tortuous in microsphere-containing than other islets. The most highly blood-perfused islets also had a higher rate of beta cell proliferation, superior beta cell function and a markedly different gene expression from other islets. Cultured islets exposed to islet endothelial cell products had a similarly increased beta cell proliferation rate, yet significantly fewer changes in gene expression than observed in the most highly blood-perfused islets.Conclusions/interpretation A novel heterogeneity between islets was observed, with superior beta cell proliferation, function and gene expression in a subpopulation of islets identified by high blood perfusion. In contrast with a previously described population of low-oxygenated, sleeping islets, which are recruited into functionality when needed, the presently described heterogeneity is shown to remain in vitro after islet isolation.

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Glucose-induced islet blood flow increase in rats: interaction between nervous and metabolic mediators

Cited by 57 publications

References 49 publications

Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging

Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging

Lack of compensatory increase in islet blood flow and islet mass in GK rats following 60% partial pancreatectomy

Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

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