Monolayer pancreatic or islet cultures are used for the development, through cloning methods, of pure islet cell preparations which are used for more critical investigations of processes involved in islet cell hormone production. We will develop these cultures from rat and human pancreas. Cultured fibroblasts from normal and diabetic donors of various ages are used to study cellular metabolism and cell proliferation. Comparisons of various metabolic functions (sugar uptake, protein synthesis and content, collagen synthesis, nucleotide incorporation into RNA and DNA, DNA content, cholesterol synthesis) and cell growth rate are made between cells from young and old donors, normal and diabetic, to see if diabetic cells behave more like aged cells. Since alterations in collagen metabolism are probably closely related to the atherosclerotic, microangiopathic, and nephropathic consequences of diabetes, cultures of fibroblasts from normal and diabetic humans are examined to determine early changes in collagen synthesis and maturation associated with the development of diabetic complications. BIBLIOGRAPHIC REFERENCES: Fujimoto, W.Y. and Ensinck, J.W.: Somatostatin inhibition of insulin and glucagon secretion in rat islet culture: reversal by ionophore A23187. Endocrinology 98: 259-262. 1976. Fujimoto, W.Y. and Teague, J.: Monolayer cell culture of human pancreatic beta cell tumor: effect of glucose and somatostatin on insulin release. Johns Hopkins Med. J. 138:1-5, 1976.