The initial step in successful islet transplantation is procurement of healthy donor islets. Given the limited number of donor pancreata selected for islet isolation and that islets from multiple donors are typically required to obtain insulin independence, it is critical to improve pancreas procurement rates and yield of islets for transplantation. Islets are delicate microorgans that are susc...

Oxidative stress plays a key role in the pathophysiological process of uremia and its complications, particularly in cardiovascular disease. The level of oxidative stress markers is known to increase as chronic kidney disease progresses and correlates significantly with the level of renal function. Hemodialysis and peritoneal dialysis are major modes of renal replacement therapy for end-stage r...

Conformational diseases are conditions that arise from the dysfunctional aggregation of proteins in non-native conformations. Type 2 diabetes mellitus can be defined as a conformational disease because a constituent beta cell protein, islet amyloid polypeptide, undergoes a change in tertiary structure followed by self-association and tissue deposition. Type 2 diabetes mellitus is associated wit...

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...

Here, we evaluate an alternative approach of preconditioning pancreatic islets before transplantation using a potent agonist of growth-hormone-releasing hormone (GHRH) to promote islet viability and function, and we explore the adrenal gland as an alternative transplantation site for islet engraftment. The endocrine microenvironment of the adrenal represents a promising niche with the unique ad...

Pancreatic beta-cell apoptosis is an important feature of islets in type 2 diabetes. Apoptosis can occur through two major pathways, the extrinsic or death receptor mediated pathway, and the intrinsic or Bcl-2-regulated pathway. Hyperglycaemia, hyperlipidaemia and islet amyloid poly-peptide (IAPP) represent important possible causes of increased beta-cell apoptosis. Hyperglycaemia induces islet...

Type-1 diabetes mellitus (T1DM) caused by autoimmune destruction of insulin-producing beta-cells essentially requires treatment with exogenous insulin therapy. Despite the education, technology and improvements in insulin formulations, patients face the ongoing life-threatening hypoglycaemia with poor quality of life as well as progressive disease leading to microand macro-vascular complication...

Type-1 diabetes mellitus (T1DM) caused by autoimmune destruction of insulin-producing beta-cells essentially requires treatment with exogenous insulin therapy. Despite the education, technology and improvements in insulin formulations, patients face the ongoing life-threatening hypoglycaemia with poor quality of life as well as progressive disease leading to microand macro-vascular complication...

Insulin producing β-cells are exposed to hypoxic stress in the early period after islet transplantation. Although it has been suggested that hypoxia leads to islet loss, the underlying mechanisms are unclear. In this study, the early transcriptional profiles of b cell response to hypoxia were determined by using the Affymetrix Murine Genome Array U74Av2 GeneChip (about 12,422 genes). In additio...