Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts.

Menger, Michael D.; Vajkoczy, Peter; Leiderer, Rosmarie; Jäger, S; Meßmer, K.

doi:10.1172/jci116002

Cited by 91 publications

(61 citation statements)

References 27 publications

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“…1A). In malignant tissue, these vessels even when fully developed have a high heterogeneity in terms of vessel caliber (Vajkoczy et al 1999), while in benign tissue microvessels reveal a progressive decrease in diameter (Menger et al 1992), similar to that observed in the present study.…”

Section: Follicular Angiogenesissupporting

confidence: 88%

Ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles

Laschke

Menger²,

Vollmar³

2002

Journal of Endocrinology

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To investigate the influence of ovariectomy on the physiological process of neovascularization of ovarian follicles, we harvested follicles with a theca interna at 48 h after pregnant mare's serum gonadotropin (PMSG) treatment of Syrian golden hamsters, for subsequent transplantation onto striated muscle tissue of chronically implanted skinfold chambers of non-ovariectomized PMSGsynchronized hamsters and bilaterally ovariectomized hamsters. Non-ovariectomized non-PMSG-treated animals served as controls. During a 2 week period after transplantation, neovascularization of these freely transplanted grafts was quantified in vivo by assessment of the newly developed microvascular follicular network, its microvessel density, the diameter of microvessels and their volumetric blood flow using fluorescence microscopic techniques. At day 3 after transplantation, capillary sprouts could be observed in all groups studied, finally developing a complete glomerulum-like microvascular network within 5-10 days. In ovariectomized animals, however, vascularization of follicular tissue was found to be accelerated and enhanced when compared with the follicles in both groups of non-ovariectomized animals. This was associated with significantly higher capillary blood perfusion, which may in part represent the graft's adaptive response to pro-angiogenic stimuli due to elevated gonadotropin levels, but might in particular be mediated by gonadotropin-induced release of vasoactive substances. Interestingly, small preantral follicles lacking a theca interna failed to vascularize in either of the groups. In conclusion, the study demonstrates that ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles.

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Section: Follicular Angiogenesissupporting

confidence: 88%

Ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles

Laschke

Menger²,

Vollmar³

2002

Journal of Endocrinology

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“…At day 28, the diameter was 8.11 ± 0.53 μm (n = 5, Fig. 2c), which is similar to the intra-islet vasculature in the pancreas 3 and other transplantation sites 17 .…”

Section: Noninvasive Imaging Of Pancreatic Islet Vascularizationsupporting

confidence: 60%

Noninvasive in vivo imaging of pancreatic islet cell biology

Speier

Nyqvist

Cabrera

et al. 2008

Nat Med

242

331

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Advanced imaging techniques have become a valuable tool in the study of complex biological processes at the cellular level in biomedical research. Here, we introduce a new technical platform for noninvasive in vivo fluorescence imaging of pancreatic islets using the anterior chamber of the eye as a natural body window. Islets transplanted into the mouse eye engrafted on the iris, became vascularized, retained cellular composition, responded to stimulation and reverted diabetes. Laserscanning microscopy allowed repetitive in vivo imaging of islet vascularization, beta cell function and death at cellular resolution. Our results thus establish the basis for noninvasive in vivo investigations of complex cellular processes, like beta cell stimulus-response coupling, which can be performed longitudinally under both physiological and pathological conditions. Adequate release of insulin by pancreatic beta cells in response to changing blood glucose levels is a vital requirement for maintaining glucose homeostasis. Failure to do so is one of the major causes of type 2 diabetes mellitus, the most common metabolic disorder in humans 1 . Under physiological conditions, insulin release is regulated by the complex interplay between glucose and a plethora of additional factors-for example, nutrients, autocrine-paracrine signaling and the continuous input from hormones and neurotransmitters 2 . Beta cells, together with other pancreatic endocrine cell types, are situated within the endocrine pancreas, that is, the islets of Langerhans, which are densely vascularized 3 and abundantly innervated 4 . Pancreatic islets, constituting 1%-2% of the pancreatic volume, are difficult to access for in vivo monitoring because they are deeply embedded and scattered in the exocrine tissue of the pancreas 5 . As a consequence, the majority of functional beta cell studies have so far been conducted in vitro on isolated islets or beta cells. Isolated islets 6 , and especially pancreatic slices 7 , allow functional studies of Author Contributions: S.S., D.N. and A.C. developed the experimental transplantation platform. S.S., D.N., O.C., J.Y., R.D.M., A.P., T.M., M.K., B.L. and A.C. did the experiments. J.W. was responsible for generating the transgenic mice. C.R. was involved in designing the transplantation protocols and writing the manuscript. S.S., D.N., I.B.L. and P.-O.B. were responsible for designing the overall experimental plan and writing the manuscript. P.-O.B. was the originator of the idea of using the anterior chamber of the eye for noninvasive in vivo imaging of pancreatic islet cell biology Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions Note: Supplementary information is available on the Nature Medicine website. Laser-scanning microscopy (LSM) of isolated islets and cell preparations has been successfully applied for imaging multiple signaling pathways in the beta cell 6 . However, intravital applications of LSM for studies of beta cell physiology have not been repo...

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“…2B), as previously documented from dissected pancreatic tissue in vitro (13,14). The increase in intra-islet vessel diameter could be part of a compensatory mechanism designed to increase blood perfusion under hyperglycemic conditions (15). It also might be an approach to optimizing endocrine signaling, ensuring that each beta cell will have direct communication with blood flow under this strong proliferative condition.…”

Section: Intraocular Islet Transplants Mirror the Adaptive Morphologicalmentioning

confidence: 73%

Reporter islets in the eye reveal the plasticity of the endocrine pancreas

Ilegems

Dicker

Speier

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance An adaptive plasticity of the insulin-secreting pancreatic beta cells, located in the islets of Langerhans, is essential for maintaining proper blood glucose homeostasis under various functional demands. Understanding the molecular mechanisms underlying the regulation of beta cell mass and function is critically dependent on an in vivo monitoring system that can continuously report on the functional status of the islets. Because direct inspection of these islets is obstructed due to the fact that they are deeply embedded and scattered within the pancreas, we propose the use of “reporter islets” transplanted into the anterior chamber of the eye, serving as optically accessible indicators of islet plasticity in the pancreas and as a tool to individually assess effectiveness of specific treatment regimens.

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Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts.

Cited by 91 publications

References 27 publications

Ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles

Ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles

Noninvasive in vivo imaging of pancreatic islet cell biology

Reporter islets in the eye reveal the plasticity of the endocrine pancreas

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