Inhibition of Renal Gluconeogenesis by Theophylline 1

Abstract

Summary

Theophylline, at a concentration from 1.0–10.0 mM, significantly inhibited glucose production from glycerol, malate, pyruvate, and α-ketoglutarate by the isolated tubules of rat renal cortex; the higher the theophylline concentration in the incubation media the smaller the glucose production rates were. Adenosine triphosphate (ATP) levels were decreased in the presence of theophylline at a concentration of 4 mM or higher. At a concentration of 1.0 mM, theophylline did inhibit glucose production from all these substrates but did not affect ATP levels in the renal tubule cell. These findings suggest that theophylline suppresses renal gluconeogenesis by a direct inhibition of certain cytosolic enzymes and/or by decreasing the levels of ATP in the cell.