Mild diabetes (blood glucose < 300 mg/100 ml) was associated with a significant reduction in hepatic glucokinase suggesting that this enzyme is the most sensitive glycolytic enzyme indicator of the diabetic state since no other tissue enzyme alterations were noted. Moderate diabetes (blood glucose, 300−500) was accompanied by glycolytic enzyme values which were significantly decreased in liver and skeletal muscles, values which were significantly increased in renal cortex, and values which were similar to control values in jejunal mucosa and heart. Thus each of these five tissues had a specific adaptive response to the diabetic state. Phosphoenolpyruvate carboxykinase was significantly increased in liver of mildly diabetic rats and in renal cortex of moderately diabetic rats. This enzyme appears to be the most sensitive gluconeogenic enzyme indicator of the diabetic state and also shows the greatest percentage increase observed for the rate-limiting gluconeogenic enzymes in livers of diabetic animals. Tolbutamide administration significantly lowered the blood glucose concentrations of mildly diabetic animals but did not alter blood glucose values of moderately or severely diabetic animals. Tolbutamide administration did not significantly alter any of the tissue enzyme activities measured in mildly, moderately, or severely diabetic animals (Endocrinology94: 27, 1974)
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Murphy et al. (1974) studied this question.