Erythropoietin exposure of isolated pancreatic islets accelerates their revascularization after transplantation

Abstract

Aims The exposure of isolated pancreatic islets to pro-angiogenic factors prior to their transplantation represents a promising strategy to accelerate the revascularization of the grafts. It has been shown that erythropoietin (EPO), a glycoprotein regulating erythropoiesis, also induces angiogenesis. Therefore, we hypothesized that EPO exposure of isolated islets improves their posttransplant revascularization. Methods Flow cytometric, immunohistochemical and quantitative real-time (qRT)-PCR analyses were performed to study the effect of EPO on the viability, cellular composition and gene expression of isolated islets. Moreover, islets expressing a mitochondrial or cytosolic H2O2 sensor were used to determine reactive oxygen species (ROS) levels. The dorsal skinfold chamber model in combination with intravital fluorescence microscopy was used to analyze the revascularization of transplanted islets. Results We found that the exposure of isolated islets to EPO (3 units/mL) for 24 h does not affect the viability and the production of ROS when compared to vehicle-treated and freshly isolated islets. However, the exposure of islets to EPO increased the number of CD31-positive cells and enhanced the gene expression of insulin and vascular endothelial growth factor (VEGF)-A. The revascularization of the EPO-cultivated islets was accelerated within the initial phase after transplantation when compared to both controls. Conclusion These findings indicate that the exposure of isolated islets to EPO may be a promising approach to improve clinical islet transplantation.

Dapagliflozin improves pancreatic islet function by attenuating microvascular endothelial dysfunction in type 2 diabetes

“…It has been reported that the increment of islet capillaries by introducing the genes Pdpk1 , Bbs4 or Irs2 in IMECs could enhance ß cell function 28–30 . Recently, a study reported that exposure of isolated islets to erythropoietin accelerated the revascularisation of islet grafts within the initial phase after transplantation to the recipient mice 31 . In our study, treatment with dapagliflozin in db/db mice increased the islet capillaries, which might thus improve ß cell function.…”

Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes

“…Of note, these are the same three processes identified in the Enrichr analysis of the human serum proteomics results (Supplementary Table 3), further supporting the notion that verapamil may also have some immune-modulatory functions. Recently, the notion of pancreas-resident or infiltrating neutrophils has been established 16 and some of the leucocyte cell surface molecules included in the neutrophil-associated processes identified by Enrichr have previously been found to be expressed in isolated pancreatic islets and islet endothelial cells 17,18 . This makes it tempting to speculate that changes in these islet-resident cells may have contributed to this surprising signature in the islets.…”

Effects of the ketogenic diet in mice with hind limb ischemia

“…2 D). This was confirmed by western blot (WB) and quantitative PCR (qPCR) results of CD31 and vascular endothelial growth factor A (VEGFA), two common indicators of tissue revascularization [ 22 ]. By performing qPCR, mRNA level of both CD31 (platelet endothelial cell adhesion molecule-1) and VEGFA was found to be significantly reduced in the ischemic hind limb tissue of mice in the KD group compared with those in the ND group (Fig.…”