Proinsulin C-peptide potentiates the inhibitory action of insulin on glucose synthesis in primary cultured rabbit kidney-cortex tubules: metabolic studies.
Effects of equimolar concentrations of proinsulin C-peptide and insulin on glucose synthesis were studied in primary cultures of rabbit kidney-cortex tubules grown in the presence of alanine, glycerol, and octanoate. The rhodamine-labeled C-peptide entered renal tubular cells and localized in nuclei, both in the presence and absence of insulin; preincubations with the unlabeled compound inhibited internalization. C-peptide did not affect glucose formation when added alone but potentiated the inhibitory action of insulin by about 20% due to a decrease in flux through glucose-6-phosphate isomerase (GPI) and (or) glucose-6-phosphatase (G6Pase). GPI inhibition was caused by: (i) increased intracellular contents of fructose-1,6-bisphosphate and fructose-1-phosphate, inhibitors of the enzyme and (ii) reduced level of the phosphorylated GPI, which exhibits higher enzymatic activity in the presence of casein kinase 2. A decrease in flux through G6Pase, due to diminished import of G6P by G6P-transporter from the cytoplasm into endoplasmic reticulum lumen, is also suggested. The data show for the first time that in the presence of insulin and C-peptide, both GPI and G6P-ase may act as regulatory enzymes of renal gluconeogenic pathway.
a Department of Metabolic Regulation, Institute of Biochemistry, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 02-096 Warsaw, Poland.
Michal
M
Usarek
Adam Konrad
AK
Jagielski
Paulina
P
Krempa
Anna
A
Dylewska
Anna
A
Kiersztan
Jakub
J
Drozak
Agnieszka
A
Girstun
Rafal Andrzej
RA
Derlacz
Jadwiga
J
Bryla
D000818:Animals; D002096:C-Peptide / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D005947:Glucose / Q000096:biosynthesis*; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011817:Rabbits
D002096:C-Peptide; D007328:Insulin; D005947:Glucose