Regulation and localization of organic osmolytes in mammalian kidney

Four organic small molecules belonging to the chemical groups of trimethylamines (betaine and glycerophosphorylcholine) and polyols (sorbitol and inositol) have been shown to act as organic osmolytes in the kidney. When measured along the corticopapillary axis, each exhibits a specific distribution pattern, indicating a specific localization and function. Studying their behaviour under vasopressin treatment in diabetes insipidus rats and after insulin treatment in diabetes mellitus rats confirmed this conclusion: AVP led to a steady increase of sorbitol and glycerophosphorylcholine over 7 days with no effect on inositol levels. Insulin treatment of diabetic rats, on the other hand, decreased sorbitol with a concomitant increase in glycerophosphorylcholine, again without any effect on tubular inositol concentrations. From this and in vitro studies it can be concluded that both hormones act by indirect mechanisms which alter interstitial osmolality. This in turn leads to a change in tubular osmolyte synthesis, uptake and release rates. In addition, the concentrations of the respective precursors glucose and choline influence the formation rates of sorbitol and betaine.