Effects of D-glucose, L-leucine, and 2-ketoisocaproate on Insulin mRNA Levels in Mouse Pancreatic Islets

To elucidate a possible mechanism for regulation of insulin mRNA levels in the pancreatic B-cell, isolated mouse pancreatic islets were cultured in the presence of either glucose, leucine, or 2-ketoisocaproate, and insulin mRNA levels were compared with insulin biosynthesis, insulin release, and islet O₂ uptake. It was observed that leucine or 2-ketoisocaproate was as effective as 20 mM glucose in supporting high insulin mRNA levels, high basal rates of insulin release or insulin synthesis, and rapid O₂ uptake. Furthermore, islets cultured with either leucine or 2-ketoisocaproate could be stimulated to increase their insulin biosynthesis by a high glucose concentration. In addition the insulin release and respiration of such islets could be increased by exposure to 2-ketoisocaproate + glutamine. It is concluded that the maintenance of high concentrations of insulin mRNA levels and high rates of insulin biosynthesis and release are all processes correlated with metabolic fluxes in islets rather than the presence of the glucose molecule per se.