Myo-lnositol and the Maintenance of β-Cell Function in Cultured Rat Pancreatic Islets

Abstract

We studied the effect of the myo-inositol content of culture media on several of the functional characteristics of cultured adult rat pancreatic islets. Variations in the ambient myo-inositol concentration had no effect on insulin content, its rate of synthesis, or its secretion in response to glucose when studied in freshly isolated islets. However, myo-inositol did inhibit the incorporation of ³H-thymidine into the DNA of the fresh islet. When islets were cultured for 6 days in the absence of myo-inositol, their basal rate of insulin secretion was elevated and they were unresponsive to an elevated glucose concentration. As the myo-inositol content of the culture medium was increased from 10 to 40 μg/ml, a progressive decrease in basal insulin secretion as well as an increase in glucose-stimulated insulin secretion was observed. Similarly, the total insulin content of cultured islets increased progressively as the myo-inositol content of the culture medium was raised. The rates of incorporation of 3H-leucine into islet protein, proinsulin, insulin, and Cpeptide were found to be twice as high in the presence of 40 μg/ml myo-inositol when compared with the rates observed in the absence of this material. The incorporation of 3H-thymidine into the DNA of cultured islets was maximal when the medium contained 20 μg/ml myo-inositol, and was decreased when concentrations above or below this value were employed. These results demonstrate that the ambient myo-inositol concentration to which cultured islets are exposed in vitro exerts a strong influence on their functional characteristics. Thus, the myo-inositol content of the culture media employed should be taken into consideration in the interpretation of any studies involving cultured pancreatic islets.