The role of intracellular cAMP in renal gluconeogenesis in view of differential action of various cAMP analogues.
Effects of various cAMP analogues on gluconeogenesis in isolated rabbit kidney tubules have been investigated. In contrast to N(6),2'-O-dibutyryladenosine-3',5'-cyclic monophosphate (db-cAMP) and cAMP, which accelerate renal gluconeogenesis, 8-bromoadenosine-3',5'-cyclic monophosphate (Br-cAMP) and 8-(4-chlorophenylthio)-cAMP (pCPT-cAMP) inhibit glucose production. Stimulatory action of cAMP and db-cAMP may be evoked by butyrate and purinergic agonists generated during their extracellular and intracellular metabolism resulting in an increase in flux through fructose-1,6-bisphosphatase and in consequence acceleration of the rate of glucose formation. On the contrary, Br-cAMP is poorly metabolized in renal tubules and induces a fall of flux through glyceraldehyde-3-phosphate dehydrogenase. The contribution of putative extracellular cAMP receptors to the inhibitory Br-cAMP action is doubtful in view of a decline of glucose formation in renal tubules grown in the primary culture supplemented with forskolin. The presented data indicate that in contrast to hepatocytes, in kidney-cortex tubules an increased intracellular cAMP level results in an inhibition of glucose production.
Jagielski
Adam K
AK
Department of Metabolic Regulation, Institute of Biochemistry, Warsaw University, Warsaw 02-096, Poland.
Podszywałow-Bartnicka
Paulina
P
Derlacz
Rafał A
RA
Bryła
Jadwiga
J
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D011817:Rabbits; D013997:Time Factors
D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D006597:Fructose-Bisphosphatase; D005947:Glucose