Noradrenergic and cholinergic reinnervation of islet grafts in diabetic rats |
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Institution: | 1. Department of Animal Physiology, University of Groningen, P.O. Box 14, 9750 AA Haren, The Netherlands;2. Department of Surgery, University of Groningen, Bloemsingel 1,9713 BZ Groningen, The Netherlands;3. Rudolf Magnus Institute for Neurosciences, University of Utrecht, P.O. Box 80040, 3508 TA Utrecht, The Netherlands;1. Department of Polymer Materials, School of Material Science and Engineering, Tianjin Polytechnic University, Tianjin 300387, China;2. Department of Materials and Environment, Faculty of Civil Engineering & Geosciences, Delft University of Technology, 2628CN Delft, The Netherlands;1. Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK;2. Centre for Ophthalmology and Vision Sciences, Institute of Human Development, University of Manchester, Manchester M13 9PT, UK;1. Precision Vaccines Program, Boston Children’s Hospital, Boston, MA, USA;2. Harvard Medical School, Boston, MA, USA;3. Institute of Clinical Research, University of Southern Denmark and Odense University Hospital, Odense, Denmark;4. Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau;5. Telethon Kids Institute, Perth, Western Australia, Australia |
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Abstract: | Grafted islets become denervated due to the islet transplantation procedure. The aim of the present study was 1) to examine whether islet grafts in the liver, the spleen, and under the kidney capsule in rats become reinnervated following the transplantation and experimental procedures used in our laboratory, 2) whether there is any difference in reinnervation at these different sites, and 3) how these results relate to previous physiological experiments. Isogeneic isolated islets were transplanted into diabetic Albino Oxford rats, resulting in normoglycaemia. After at least 5 wk, graft-receiving organs were removed and several antibodies were employed to detect insulin, neuronspecific proteins, and cholinergic and noradrenergic nerve fibers. Islets in all three receiving organs contained viable insulin-positive B-cells. Neuron-specific enolase (NSE) as well as the growth-associated protein B-50 was observed at all sites. The cholinergic marker choline acetyltransferase (ChAT) was localized in islets grafts at all sites, but with the lowest density in the spleen. Staining for the noradrenergic markers tyrosine hydroxylase (TH) and dopamine-phydroxylase (DBH) was observed in islet grafts at all sites with the lowest density in grafts under the kidney capsule. All these neurochemical substances were most frequently observed in fibers associated with blood vessels, which may be the route along which nerves grow into the graft. It can be concluded that 1) islet grafts in the liver, in the spleen and under the kidney capsule become reinnervated; 2) the innervation pattern of the islet grafts differs only slightly from that in the control pancreatic islets; and 3) in combination with our previously physiological data, we can conclude that these nerve fibers are, at least partly, functionally active. |
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