Studies of gluconeogenesis were carried out with isolated tubules prepared from the renal cortex of fasted rats. A study of the metabolic characteristics of this preparation upon incubation at 37° revealed a sustained respiratory rate, a constancy of ATP levels, and a linear rate of gluconeogenesis. Virtually no glucose synthesis was observed unless appropriate substrates were added; succinate and α-ketoglutarate were the most effective precursors. The addition of phenformin to the suspension of isolated tubules led to a decline of O2 uptake and ATP content in the absence and in the presence of added substrate. In the presence of succinate, there was a close correlation between the ATP content and the rate of gluconeogenesis. The data indicate that the phenformin-induced inhibition of gluconeogenesis is secondary to limitation of ATP generation rather than a direct effect on the enzymatic sequence leading to new glucose formation or to limited availability of reducing equivalents.

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