Altered TNF-[Alpha] glucose, insulin, and amino acids in islets of Langerhans cultured in a microgravity model system

Altered TNF-[Alpha], glucose, insulin, and amino acids in islets of Langerhans cultured in a microgravity model system. Am J Physiol Endocrinol Metab 280: E92-E102, 2001.--The present studies were designed to determine effects of a microgravity model system upon lipopolysaccharide (LPS)-stimulated tumor necrosis factor-[Alpha] (TNF-[Alpha]) activity and indexes of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1,726 [+ or -] 117, 150 islet equivalent units) from Wistar-Furth rats were treated as 1) high aspect ratio vessel (HARV) cell culture, 2) HARV plus LPS, 3) static culture, and 4) static culture plus LPS. TNF-[Alpha] (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures; yet the increase was more pronounced in the static culture group (P [is less than] 0.05). A decrease in insulin concentration was demonstrated in the LPS-stimulated HARV culture (P [is less than] 0.05). We observed a greater glucose concentration and increased disappearance of arginine in islets cultured in HARVs. Although nitrogenous compound analysis indicated a ubiquitous reliance on glutamine in all experimental groups, arginine was converted to ornithine at a twofold greater rate in the islets cultured in the HARV microgravity model system (P [is less than] 0.05). These studies demonstrate alterations in LPS-induced TNF-[Alpha] production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV. These alterations in fuel homeostasis may be promulgated by gravity-averaged cell culture methods or by three-dimensional cell assembly. tumor necrosis factor-[Alpha]; cytokines; diabetes; amino acids