Introduction: Islets of Langerhans are well innervated and vascularized, however, the regulatory mechanisms for innervation and vascularization are not well clarified. In mice deficient for proglucagon-derived peptides (Gcggfp/gfp: GCGKO), islet cells that express green fluorescent protein (GFP) under the control of glucagon promoter (α-cells) display hyperplasia and number of islets is increased. The present study was aimed to clarify role of the proglucagon-derived peptides in innervation and vascularization into islets.
Method: Immunohistochemical analyses for pancreata of GCGKO and heterozygous Gcggfp/+mice were performed by using antibodies for platelet-endothelial cell adhesion molecule-1 (PECAM1), vascular endothelial growth factor (VEGF), tyrosin hydroxylase (TH), laminin, synapsin I, neuropeptide Y (NPY) and insulin.
Results: Neuronal fibers positive for NPY and/or TH were identified in and around islets of both Gcg-gfp/+ and GCGKO mice. Basement membranes positive for laminin were present around the islets and blood vessels. Synapsin positive spots were mostly identified nearby blood vessels and α-cells. Some of the non-α-cells were positive for TH. NPY was detected in some of α-cells, β-cells and cells negative for both glucagon and insulin. VEGF were expressed in both α-cells and β-cells. In GCGKO islets that contained mostly GFP positive α-cells and β-cells, numbers of blood vessels and nerves, as well as signal intensities of VEGF, NPY, and TH were reduced.
Conclusion: Proglucagon-derived peptides are not an absolute prerequisite for innervation and vascularization into islets. However, reduced innervation and vascularization into malformed GCGKO islets consisted of mostly GFP positive α-cells suggested that non-α populations play regulatory role in establishing networks of nerves and blood vessels in islets of Langerhans.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
Figure 1. Islets of Langerhans in glucagonGFP knock-in mice. Green: GFP autofluorescence, Red: Insulin.