The pancreatic islet comprises endocrine, vascular, and neuronal cells. Signaling among these cell types is critical for islet function. The extracellular matrix (ECM) is a key regulator of cell-cell signals, and while some islet ECM components have been identified, much remains unknown regarding its composition. We investigated whether hyaluronan, a common ECM component that may mediate inflam...

Type 2 diabetes is characterized by islet dysfunction resulting in hyperglycemia, which can then lead to further deterioration in islet function. A possible mechanism for hyperglycemia-induced islet dysfunction is the accumulation of advanced glycation end products (AGE). The DBA/2 mouse develops pancreatic islet dysfunction when exposed to a high glucose environment and/or obesity-induced insu...

In type 1 diabetes, the pancreatic islets are an important site for therapeutic intervention because immune infiltration of the islets is well established at diagnosis. Therefore, understanding the events that underlie the continued progression of the autoimmune response and islet destruction is critical. Islet infiltration and destruction is an asynchronous process, making it important to anal...

Islet amyloid deposition in type 2 diabetes is associated with reduced beta-cell mass. Therefore, interventions aimed at reducing islet amyloid formation may help preserve beta-cell mass in type 2 diabetes. Rosiglitazone and metformin act by different mechanisms to improve insulin sensitivity and thereby reduce beta-cell secretory demand, resulting in decreased release of insulin and islet amyl...

Two types of transplants are offered to patients with complicated insulin dependent diabetes mellitus: a) whole pancreas transplantation, b) pancreatic islet transplantation. A total of 29000 whole pancreas transplantations and 1500 islet transplantations have been performed worldwide until today. Patient survival for whole pancreas recipients is 85% five years after transplantation, whereas ve...

Islet allotransplantation can provide prolonged insulin independence in selected individuals with type 1 diabetes. Whether islet transplantation also restores hypoglycemic counterregulation is unclear. To determine if hypoglycemic counterregulation is restored by islet transplantation, we studied hormone responses and hypoglycemic symptom recognition in seven insulin-independent islet transplan...

Assays were developed to detect cell-mediated immune destruction of pancreatic islet beta cells by lymphoid cells isolated from diabetic BioBreeding/Worcester (BB/W) rats. Splenic lymphoid cells from diabetic (D), diabetes-prone (DP), and diabetes-resistant (DR) BB/W rats were incubated for 2 days with monolayer cultures of major histocompatibility complex (MHC)-compatible Wistar-Furth (WF) rat...

Intra- and intermolecular spreading of T cell responses to autoantigens has been implicated in the pathogenesis of autoimmune diseases. Therefore, we questioned whether T cell responses from subjects identified as at-risk (positive for autoantibody reactivity to islet proteins) for the development of type 1 diabetes, a cell-mediated autoimmune disease, would demonstrate intermolecular Ag spread...

Type 2 diabetes is characterized by impaired insulin secretion from pancreatic β-cells. Quantification of the islet area in addition to the insulin-positive area is important for detailed understanding of pancreatic islet histopathology. Here we show computerized automatic recognition of the islets of Langerhans as a novel high-throughput method to quantify islet histopathology. We utilized sta...

Islet transplantation is a promising therapy for type 1 diabetes mellitus; however, success rates in achieving both short- and long-term insulin independence are not consistent, due in part to inconsistent islet quality and quantity caused by the complex nature and multistep process of islet isolation and transplantation. Since the introduction of the Edmonton Protocol in 2000, more attention h...