Effect of various aminoglycoside antibiotics on glucose formation in isolated rabbit kidney-cortex tubules

The effect of six aminoglycoside antibiotics on the rate of gluconeogenesis was studied in isolated rabbit kidney-cortex tubules incubated with various substrates. All antibiotics studied did not affect glucose formation from both malate and 2-oxoglutarate. The rank order of the drug-induced inhibition of glucose formation from lactate, pyruvate and propionate was the following: neomycin = gentamicin greater than tobramycin greater than kanamycin = amikacin greater than streptomycin. This in principle corresponds to their ability to diminish pyruvate carboxylation in isolated kidney-cortex mitochondria, as well as to their known nephrotoxic potential observed in vivo. Aminoglycoside antibiotics decreased the respiration of tubule suspension incubated with various substrates. However, the rank order of the inhibition by antibiotics of oxygen uptake was different from that observed for gluconeogenesis, suggesting that the rate of energy generation does not limit glucose formation under conditions studied.