Effect of Prolonged-acting Insulin on Intestinal and Hepatic Metabolism of 4-nitrophenol in STZ-Induced Experimental Diabetes

Metabolism of xenobiotics can be influenced by a number of factors, among which hyperglycaemia caused by the insufficiency of the glucose metabolism (e.g., diabetes mellitus, impaired glucose tolerance, resistance) should be emphasized. Not only the pathological condition, but the compounds administered as treatment can alter the metabolic profile of certain pharmacons. While the rapid-acting insulin exerts its effect mainly with the acute change of the blood glucose level, the prolonged-acting insulin affects in a more complex way. Because of its simple and well-characterised metabolic profile, the p-nitrophenol (PNP) is a model compound for the investigation of conjugative (glucuronidation and sulfation) transformations. An in vivo experimental study was evaluated to determine the quantities of the forming p – p-nitrophenyl-glucuronide (PNP-G) and p-nitrophenol-sulfate (PNP-S) conjugates in small intestinal perfusate and bile samples in physiologic condition, in experimental diabetes (streptozotocine (STZ) induced), and in compensated diabetes with prolonged–acting insulin. In these investigations, the formed metabolic profile was influenced by the individual effect of the administered insulin.