Somatostatin-like immunoreactivity (SRIF-LI) has been shown to be widely distributed in nerve endings in the central nervous system (CNS) as well as being present in D cells of the pancreas and gut. This peptide and others with a similar distribution are thought to function as neuromodulators in the brain and have paracrine or endocrine effects in the GI tract. Pancreatic and GI SRIF-LI appears to have a role in modulating nutrient homeostasis, the specific role of CNS SRIF-LI is unknown. The proposed studies are designed to investigate the effects of CNS and systemic manipulations that alter glucose homeostasis on CNS and GI SRIF content and release and obtain information on how these effects are neurally mediated. Models of experimental diabetes (Streptozotocin induced), obesity (VMH lesioned and Zucker rats) and centrally induced, non-diabetic hyperglycemia (central bombesin or 2-Deoxyglucose) will be studied. In vivo GI SRIF-LI release and in vitro hypothalamic and cerebral cortical SRIF-LI release, together with SRIF-LI content in the GI tract and CNS, will provide a measure of SRIF-LI response to the manipulations of glucose homeostasis proposed. Autonomic blocking agents will be used to define the mode of neural mediation of GI changes secondary to CNS manipulation.