Dataset Information

Vascular endothelial growth factor-a and islet vascularization are necessary in developing, but not adult, pancreatic islets.

ABSTRACT: Pancreatic islets are highly vascularized mini-organs, and vascular endothelial growth factor (VEGF)-A is a critical factor in the development of islet vascularization. To investigate the role of VEGF-A and endothelial cells (ECs) in adult islets, we used complementary genetic approaches to temporally inactivate VEGF-A in developing mouse pancreatic and islet progenitor cells or in adult ?-cells. Inactivation of VEGF-A early in development dramatically reduced pancreatic and islet vascularization, leading to reduced ?-cell proliferation in both developing and adult islets and, ultimately, reduced ?-cell mass and impaired glucose clearance. When VEGF-A was inactivated in adult ?-cells, islet vascularization was reduced twofold. Surprisingly, even after 3 months of reduced islet vascularization, islet architecture and ?-cell gene expression, mass, and function were preserved with only a minimal abnormality in glucose clearance. These data show that normal pancreatic VEGF-A expression is critical for the recruitment of ECs and the subsequent stimulation of endocrine cell proliferation during islet development. In contrast, although VEGF-A is required for maintaining the specialized vasculature observed in normal adult islets, adult ?-cells can adapt and survive long-term reductions in islet vascularity. These results indicate that VEGF-A and islet vascularization have a lesser role in adult islet function and ?-cell mass.

SUBMITTER: Reinert RB

PROVIDER: S-EPMC3837071 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Vascular endothelial growth factor-a and islet vascularization are necessary in developing, but not adult, pancreatic islets.

Reinert Rachel B RB Brissova Marcela M Shostak Alena A Pan Fong Cheng FC Poffenberger Greg G Cai Qing Q Hundemer Gregory L GL Kantz Jeannelle J Thompson Courtney S CS Dai Chunhua C McGuinness Owen P OP Powers Alvin C AC

Diabetes 20130724 12

Pancreatic islets are highly vascularized mini-organs, and vascular endothelial growth factor (VEGF)-A is a critical factor in the development of islet vascularization. To investigate the role of VEGF-A and endothelial cells (ECs) in adult islets, we used complementary genetic approaches to temporally inactivate VEGF-A in developing mouse pancreatic and islet progenitor cells or in adult β-cells. Inactivation of VEGF-A early in development dramatically reduced pancreatic and islet vascularizatio ...[more]

PMID: 23884891

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Project description:BackgroundImproving islet graft revascularization has become a crucial task for prolonging islet graft survival. Endothelial cells (ECs) are the basis of new microvessels in an isolated islet, and EC coating has been demonstrated to improve the vascularization and survival of an islet. However, the traditional method of EC coating of islets has low efficiency in vitro. This study was conducted to evaluate the effect of a polyglycolic acid (PGA) scaffold on the efficiency of islet coating by ECs and the angiogenesis in the coated islet graft.MethodsA PGA fibrous scaffold was used for EC coating of islet culture and was evaluated for its efficiency of EC coating on islets and islet graft angiogenesis.ResultsIn in vitro experiments, we found that apoptosis index of ECs-coating islet in PGA group (27% ± 8%) was significantly lower than that in control group (83% ± 20%, P < 0.05) after 7 days culture. Stimulation index was significantly greater in the PGA group than in the control group at day 7 after ECs-coating (2.07 ± 0.31 vs. 1.80 ± 0.23, P < 0.05). vascular endothelial growth factor (VEGF) level in the PGA group was significantly higher than the coating in the control group after 7 days culture (52.10 ± 13.50 ng/ml vs. 16.30 ± 8.10 ng/ml, P < 0.05). Because of a tight, circumvallated, adhesive and three-dimensional growth microenvironment, islet cultured in a PGA scaffold had higher coating efficiency showing stronger staining intensity of enzyme than those in the control group after 14 days of culture following ECs-coating. For in vivo study, PGA scaffold significantly prolonged the average survival time of EC-coated islet graft after transplantation compared with control group (15.30 ± 5.60 days vs. 8.30 ± 2.45 days, P < 0.05). The angiogenesis and area of survived grafts were more in the PGA group compared with the control group by measuring the mean microvessel density (8.60 ± 1.21/mm2 vs. 5.20 ± 0.87/mm2, P < 0.05). In addition, expression of VEGF and tyrosin-protein kinase receptor (Tie-2) gene increased in PGA scaffold group than that in control group by real-time reverse transcription-polymerase chain reaction analysis.ConclusionsThese results demonstrate that the efficiency of EC coating of islets was successfully increased by culturing ECs on a PGA scaffold. This method enhances the function, survival, and vascularization of isolated islets in vitro and in vivo.

Dataset Information

Vascular endothelial growth factor-a and islet vascularization are necessary in developing, but not adult, pancreatic islets.

Publications

Vascular endothelial growth factor-a and islet vascularization are necessary in developing, but not adult, pancreatic islets.

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