9305554 Sheridan Recent studies have indicated the existence of multiple forms of somatostatin, a peptide originally isolated from the brain and found to contain 14-amino acid (from gene I) and to inhibit growth hormone secretion, but subsequently found to be located in the pancreas, gastrointestinal tract and elsewhere of many vertebrates. The special significance of multiple forms (14-amino acid forms and N-terminally extended forms) of somatostatins, and the roles of these factors in regulation of lipid metabolism, have yet to be determined. With the proposed work, Dr. Sheridan seeks to evaluate the role of somatostatins in the coordination of lipid metabolism in fish. Fish offer a unique system for the study of these questions because of their evolutionary position, diversified lipid storage strategy (partitioning of lipid reserves among several depots: mesenteric fat, liver and dark muscle), and segregated endocrine pancreas (Brockman body) possessing abundant amounts of N-terminally extended somatostatin (somatostatin-25; from gene II). He will demonstrate for the first time the differential effects of gene I and gene II somatostatins on lipid metabolism. This analysis will demonstrate important interactions among the various pancreatic hormones (e.g., somatostatins, insulin, glucagon, pancreatic polypeptide) and evaluate the direct effects, including cellular mode of action, of somatostatins on hepatic lipolysis. He also will evaluate for the first time the binding of somatostatin to liver, a major lipid depot of fish, and examine alterations in somatostatin binding characteristic (affinity, capacity) in response to nutrient (glucose) and hormonal (INS, GLU) treatment. While pertaining specifically to fish, this research will provide novel information concerning somatostatin phsyiology generally. These results will contribute significantly to the basic understanding of hormonal control of hepatic lipid metabolism and provide important insight into the evolution of lipid metabolism control schemes. ***
