Increased levels of reactive oxygen species (ROS) lead to dysfunction and subsequent loss of insulin-producing beta cells in pancreatic islets. Several lines of evidence support the importance of increased NADPH oxidase (NOX) activity as one of the contributing factors to elevated levels of ROS in beta cells. NOX-1 activity has been established as one of the sources of ROS in beta cells under experimental diabetic conditions. A contribution of NOX-1 to beta cell dysfunction in human diabetes is supported by preliminary studies. To further validate these observations as a first step we seek to establish the pattern of expression NOX-1 in normal and diabetic human islets. We hypothesize that NOX-1 will be elevated in diabetic islets. NOX-1 expression will be studied in relation to both the specific cells within pancreatic islets (beta cells, alpha cells) identified using well established specific protein markers for each phenotype as well as to the endocrine “sufficiency” status of such cells. In order to specifically examine qualitatively and quantitatively islets from 6 non-diabetic controls, 6 type 2 diabetes, 6 type 1 diabetes of short and 6 of long duration as well as 6 autoantibody positive would be employed; hence a total of 30 donors will be included in this study. Paraffin embedded 7 ìm thick sections of pancreas will be immunostained, using a protocol previously developed specifically for nPOD specimens. Commercially available antibodies raised against human NOX-1, insulin and glucagon will be used. Stained sections will be subjected to microscopic evaluation using both conventional fluorescent microscope and confocal microscope. A qualitative and quantitative analysis of the obtained images will be employed. We expect that an increase in expression NOX-1 will be observed in islets obtained diabetic and autoantibody positive donors.