Improved outcome of islet transplantation in insulin-treated diabetic mice: effects on beta-cell mass and function

Merino, Juan Francisco Roldán; Nacher, Víctor; Raurell, M; Aranda, Osvaldo Luiz; Soler, Joan; Montanya, Eduard

doi:10.1007/s001250050781

Cited by 36 publications

(36 citation statements)

References 27 publications

(36 reference statements)

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“…Although ␤-cell death in the immediate posttransplantation period may explain some of the difference (46), low tissue oxygen tension may also contribute later on by suppressing insulin produc-tion. In accord with previous findings (11,12,31,47,48), an even further decrease in graft insulin content was observed in the diabetic animals, compared with nondiabetic animals, in grafts implanted beneath the renal and the splenic capsules. In addition, in perfusion experiments of graft-bearing kidneys from diabetic mice, glucose-stimulated insulin secretion was markedly diminished when compared with that seen in nondiabetic control mice (49).…”

Section: Discussionsupporting

confidence: 91%

Markedly Decreased Oxygen Tension in Transplanted Rat Pancreatic Islets Irrespective of the Implantation Site

Carlsson¹,

Palm²,

Andersson³

et al. 2001

Diabetes

367

303

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In this study, we syngeneically transplanted islets to three different implantation sites of diabetic and nondiabetic rats, then 9 -12 weeks later we measured the blood perfusion and compared the tissue partial pressure of oxygen (PO 2 ) levels of these transplanted islets to endogenous islets. Modified Clark microelectrodes (outer tip diameter 2-6 m) were used for the oxygen tension measurements, and islet transplant blood perfusion was recorded by laser-Doppler flowmetry (probe diameter 0.45 mm). The islet graft blood perfusion was similar in all islet grafts, irrespective of the implantation site. In comparison, the three implantation organs (the kidney cortex, liver, and spleen) differed markedly in their blood perfusion. There were no differences in islet graft blood perfusion between diabetic and nondiabetic recipients. Within native pancreatic islets, the mean PO 2 was ϳ40 mmHg; however, all transplanted islets had a mean PO 2 of ϳ5 mmHg. The oxygen tension of the grafts did not differ among the implantation sites. In diabetic recipients, an even lower PO 2 level was recorded in the islet transplants. We conclude that the choice of implantation site seems less important than intrinsic properties of the transplanted islets with regard to the degree of revascularization and concomitant blood perfusion. Furthermore, the mean PO 2 level in islets implanted to the kidney, liver, and spleen was markedly decreased at all three implantation sites when compared with native islets, especially in diabetic recipients. These results are suggestive of an insufficient oxygenization of revascularized transplanted islets, irrespective of the implantation site. Diabetes 50: -495, 2001A factor of potential importance in the failure of islet grafts is poor or inadequate engraftment of the islets in the implantation organ. Normally, pancreatic islets have a dense glomerular-like capillary network in which the capillaries course through the islet in a tortuous fashion that is ideal for the delivery of oxygen and nutrients to the islet cells and for the dispersal of the secreted hormones to the target organs (1,2). This pancreatic islet angioarchitecture entails a blood perfusion of the pancreatic islets that is 10 times higher than that in the exocrine pancreas and similar to that seen in the renal cortex (ϳ5-7 ml ⅐ min Ϫ1 ⅐ g -1 ) (3-6). However, during the process of isolation and in vitro culture of pancreatic islets preceding transplantation, the islet vasculature dedifferentiates or degenerates (7,8). Therefore, immediately after transplantation, the pancreatic islets are supplied with oxygen and nutrients solely by diffusion from the surrounding tissues. The revascularization process is initiated within a few days, and the islets are generally thought to be fully revascularized by 1 month posttransplantation (9,10). We had previously observed markedly decreased oxygen tension in islets transplanted beneath the renal capsule at 1 month posttransplantation, a decrease that was even more pronounced in diabetic animals (11)....

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Section: Discussionsupporting

confidence: 91%

Markedly Decreased Oxygen Tension in Transplanted Rat Pancreatic Islets Irrespective of the Implantation Site

Carlsson¹,

Palm²,

Andersson³

et al. 2001

Diabetes

367

303

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“…Many factors play a role in early beta cell damage and death after transplantation, including islet injury during isolation [4,5], technical problems in the transplantation process [6], inadequate mass of islet tissue [7], hypoxia [8], exposure to the recipient hyperglycaemia [9], absence of survival factors present in the non-endocrine pancreas [10], or disruption of islet cellular connections to extracellular matrix [11]. In addition, non-specific inflammation at the grafted site, involving the expression of pro-inflammatory cytokines, is considered to play a role in early graft failure [4,5,12,13].…”

Section: Introductionmentioning

confidence: 99%

Adenoviral overproduction of interleukin-1 receptor antagonist increases beta cell replication and mass in syngeneically transplanted islets, and improves metabolic outcome

et al. 2007

Self Cite

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“…4B) suggests that FGF-21 treatment increased insulin sensitivity, which might well decrease the β-cell load and rescue β-cells from apoptosis, as has previously been reported. [25][26][27] On the other hand, as FGF-21 treatment has been found to have a direct cytoprotective effect on pancreatic β-cells, 15 FGF-21 might well similarly affect the graft in our transplantation model. We attempted to examine this immunohistologically, but it was not possible to find statistical difference because only 80 islets were transplanted in our experiment.…”

Section: Discussionmentioning

confidence: 87%

FGF-21 enhances islet engraftment in mouse syngeneic islet transplantation model

Uonaga

Toyoda

Okitsu

et al. 2010

Islets

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Improved outcome of islet transplantation in insulin-treated diabetic mice: effects on beta-cell mass and function

Cited by 36 publications

References 27 publications

Markedly Decreased Oxygen Tension in Transplanted Rat Pancreatic Islets Irrespective of the Implantation Site

Markedly Decreased Oxygen Tension in Transplanted Rat Pancreatic Islets Irrespective of the Implantation Site

Adenoviral overproduction of interleukin-1 receptor antagonist increases beta cell replication and mass in syngeneically transplanted islets, and improves metabolic outcome

FGF-21 enhances islet engraftment in mouse syngeneic islet transplantation model

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