Glucagon-like Peptide 1 (GLP-1) and glucagon shares the same precursor molecule proglucagon, but each arises from a distinct posttranslational process in a tissue-specific manner. Recently GLP-1 has been shown to be co-expressed with glucagon in pancreatic islet cells. Our preliminary data showed GLP-1 was progressively up-regulated in pancreatic islets during type 2 diabetes development. These data suggest intra-islet GLP-1 production may have an impact on the clinical and pathophysiological processes of these diseases and may be a target for therapeutic approaches. This project is thus designed to investigate this matter in human type 1 and type 2 diabetic patients. In addition, since GLP-1 based drugs, incretins, have been developed and approved for clinical use, it is thus essential to investigate their impact on intra-islet GLP-1 production. The main objectives of this project are thus 1) To investigate whether GLP-1 vs glucagon production in pancreas of human has changed with the development of type 1 and type 2 diabetes; and 2) To investigate whether the GLP-1 based therapies (i.e., incretin therapy) had any impact on the relative production of GLP-1 vs glucagon. To accomplish the goals, pancreatic tissues from normal, type 1 diabetic, type 2 diabetic without incretin treatment and type 2 diabetic with incretin treatment will be analyzed by immunofluorescence staining. The GLP-1 vs glucagon expression will be quantified and analyzed for statistical significance. In addition, the matching blood samples will be used to obtain physiological data related to glucose regulation. The results will help us understand the complete effect of incretin drugs, and identify potential safety issues. Therefore, the study will not only advance our knowledge on the regulation of intra-islet GLP-1 production in diabetes, but also have significant impact on the clinical practice regarding current use of incretins.