Modulation of pancreatic islet function in a microgravity analog

Abstract

Endocrines, cytokines, and nutrients play essential roles in maintaining muscle in extended space flight. We determined the influence of a microgravity analog upon nutritional and immunologic function of pancreatic endocrine cells. High Aspect Ratio Vessel (HARV) was used as a microgravity analog. Human islets of Langerhans were cultivated in the HARV or in static plate (PLT) up to 48 hours at 37OC in 5% CO2 and 95% H2O. Islets were treated with hydrocortisone (HCS) and a mixture of 11 essential amino acids (AA). Insulin, glucagon, and 41 amino acids metabolites were assessed in supernatants. In islet tissue we determined gene expression of insulin, glucagon, somatostatin, tumor necrosis factor (TNF)-α, TNF-α receptor (rTNF-α), interleukin (IL)-1â, IL-1 receptor (rIL-1), and IL-1 receptor antagonist (raIL-1). We observed significantly (P<0.05) lower glutamine concentration in PLT (0.63±0.2ìmol/mL) compare to HARV (1.3±0.2 ìmol/mL). Additionally, increased arginine/ornithine ratio was observed in PLT but not HARV. We conclude that a microgravity analog alters insulin gene expression. A combination of cell culture and endocrine factors altered gene expression of glucagon, somatostatin, IL-1β, rIL-1, raIL-1, and TNF-α, but not TNF-α receptor. HCS treatment is able to recover suppressed insulin, glucagon, somatostatin, and IL-1â gene expression in both HARV and PLT cultures. Supported by NIH R15 GM62795-03 and NSBRI through Cooperative Agreement NCC 9 58 with NASA.