The responses of livers from rats with type 2 diabetes to alanine (gluconeogenesis and ammonia detoxification) and other gluconeogenic substrates were investigated. The experimental system was the isolated perfused rat liver. Neonatal type 2 diabetes was induced with streptozotocin. Ammoniogenesis from endogenous substrates was 610% higher in livers from diabetic rats when compared to the control condition. Alanine (2.5 mM) ammoniogenesis was 285% higher in livers of diabetic rats. Gluconeogenesis from the following substrates was smaller in the liver of diabetic rats: Alanine (?43.5%), lactate (?28.3%) and glycerol (?30.5%). Pyruvate gluconeogenesis was normal. The high rate of ammoniogenesis explains the moderate hyperammonemia of type 2 diabetic rats. The enzymatic machinery of the gluconeogenic pathway of type 2 diabetic rats seems to be adapted to low rates of glucose removal by extrahepatic tissues. A significant contribution of gluconeogenesis to the fasting hyperglycemia can be expected only by short-term up-regulation mechanisms.
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