Zonation of gluconeogenesis, ketogenesis and intracellular pH in livers from normal and diabetic ketoacidotic rats: evidence for intralobular redistribution of metabolic events in ketoacidosis

The intralobular distribution of metabolism was examined in the livers from rats with severe diabetic ketoacidosis (DKA), perfused at pH 6.8, and comp ared with that in livers from normal starved animals perfused at either pH 7.4 or 6.8. With lactate and palmitate as substrates, the perivenous uptake of periportally synthesized glucose seen in normal livers at pH 7.4 was ab olished during DKA; indeed, gluconeogenesis was most active in the periveno us region. Whereas in normal livers perfused at pH 7.4 the periportal regio n showed a markedly elevated intracellular pH (pH(i)) compared with the per ivenous zone, this distribution of pH(i) was reversed in DKA, with an inter mediate distribution in normal livers perfused at pH 6.8. 3-Hydroxybutyrate was generated throughout the lobule. Some acetoacetate generated periporta lly was converted to 3-hydroxybutyrate more perivenously. A steep gradient of oxygen uptake along the radius of the lobule was apparent in all three g roups; oxygen uptake was greatly decreased perivenously despite adequate ox ygen supply. These findings are consistent with our previous observations o f the lobular co-location of high pH(i) and gluconeogenesis, and might offe r an explanation of how high gluconeogenic rates can continue in spite of s evere systemic acidosis in DKA. The findings provide direct evidence for a marked redistribution of intralobular metabolism in DKA.