Polyol metabolism in monkey-kidney epithelial-cell cultures. Sorbitol synthesis.

Abstract

An investigation of polyol synthesis by monolayer cultures of monkey kidney epithelium cells was undertaken as a consequence of the observation that these cells accumulated high concentrations of acyclic hexitols (200–600 μmol/g protein) when incubated in media containing elevated glucose [590 mg‐% (w/v)] concentrations. It was established that the acyclic hexitol which accumulated when monkey kidney epithelial cell cultures were incubated in high glucose medium was sorbitol. The involvement of the polyol pathway of metabolism in this phenomenon was implicated from radioactivity incorporation experiments using [U‐14C]glucose substrate (the specific radioactivity of the sorbitol product was 92 % of the specific radioactivity of the added glucose) and from studies involving the use of the aldose reductase inhibitor 3,3′‐tetramethylene glutaric acid, which caused marked inhibition of polyol synthesis. The intracellular glucose concentration was found to be an important factor regulating the steady state concentrations of the pathway intermediates sorbitol and fructose in monkey kidney epithelial cell cultures. Changes in the oxygen tension in the incubation medium or the presence of the hormones vasopressin, insulin or epinephrine were shown not to affect the concentrations of sorbitol or fructose in monkey kidney epithelial cell cultures incubated in media containing a high glucose concentration. Cultures of HeLa Cells, goldfish testes fibroblasts, or ascites tumor cells did not exhibit the same capacity as monkey kidney epithelial cell cultures for sorbitol synthesis. To our knowledge, the present findings constitute the first reported example of polyol pathway activity in cells in monolayer culture.