The Edmonton trials have brought about a marked improvement in the short-term rate of success of islet transplantation with rates of insulin-independence of 80% at 1-year being reported by several institutions worldwide. Unfortunately, this rate consistently decreases to 10-15% by 5 years post-transplantation. Several mechanisms have been proposed to explain this apparent 'islet exhaustion', bu...

We have previously shown that co-transplantation of islets and Mesenchymal Stem Cells (MSCs) improves islet graft function and revascularisation, which was associated with the maintenance of normal islet morphology. The aim of the current study was to determine whether maintaining islet morphology in the absence of additional islet-helper cells would improve transplantation outcome in diabetic ...

The receptor tyrosine kinase c-Kit plays an integral role in maintaining b-cell mass and function. Although c-Kit receptor signaling promotes angiogenesis in multiple cell types, its role in islet vasculature is unknown. This study examines the effects of c-Kit–mediated vascular endothelial growth factor isoform A (VEGF-A) and islet vascularization on b-cell function and survival using in vitro...

The microscopic image analysis of pancreatic Islet of Langerhans morphology is crucial for the investigation of diabetes and metabolic diseases. Besides the general size of the islet, the percentage and relative position of glucagon-containing alpha-, and insulin-containing beta-cells is also important for pathophysiological analyses, especially in rodents. Hence, the ability to identify, quant...

The aim of this study was to evaluate Exendin-4 (EX-4) effects on islet volume and number in the mouse pancreas. Thirty-two healthy adult male NMRI mice were randomly divided into control and experimental groups. EX-4 was injected intraperitoneally (i. p.) at doses of 0.25 (E1 group), 0.5 (E2 group), and 1 μg/kg (E3 group), twice a day for 7 consecutive days. One day after the final injection, ...

Pancreatic islet transplantation is an emerging therapy for type 1 diabetes. To survive and function, transplanted islets must revascularize because islet isolation severs arterial and venous connections; the current paradigm is that islet revascularization originates from the transplant recipient. Because isolated islets retain intraislet endothelial cells, we determined whether these endothel...

OBJECTIVES Activated thrombin-activatable fibrinolysis inhibitor is a coagulation factor in some thrombotic diseases. However, available data on whether thrombin-activatable fibrinolysis inhibitor is activated in islet transplant are limited. In this study, changes of plasma-activated thrombin-activatable fibrinolysis inhibitor levels in instant blood-mediated inflammatory reaction after islet ...

Islet transplantation is a promising therapy for treatment of type 1 diabetes. A real breakthrough was reported when the Edmonton protocol was introduced in 2000. This protocol induced insulin independence in diabetic patients for 1 year (1). Although these clinical islet transplantations demonstrated the application of the technique, the long-term function of the islet grafts was not that succ...

A significant portion of the genome is transcribed as long noncoding RNAs (lncRNAs), several of which are known to control gene expression. The repertoire and regulation of lncRNAs in disease-relevant tissues, however, has not been systematically explored. We report a comprehensive strand-specific transcriptome map of human pancreatic islets and β cells, and uncover >1100 intergenic and antisen...

Islet transplantation is an attractive treatment for selected patients with brittle type 1 diabetes. In the clinical setting, intraportal transplantation predominates. However, due to extensive early islet cell death, the quantity of islets needed to restore glucose homeostasis requires in general a minimum of two donors. Moreover, the deterioration of islet function over time results in few in...