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Proinsulin C-peptide potentiates the inhibitory action of insulin on glucose synthesis in primary cultured rabbit kidney-cortex tubules: Metabolic studies

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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.
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Keywords: culture primaire de cellules de tubules de cortex rénal; gluconeogenesis; insulin; insuline; intermediary metabolites; métabolites intermédiaires; néoglucogenèse; peptide-C de la pro-insuline; primary cultured kidney-cortex tubules; proinsulin C-peptide

Document Type: Research Article

Affiliations: 1: Department of Metabolic Regulation, Institute of Biochemistry, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 02-096 Warsaw, Poland. 2: Department of Molecular Biology, Institute of Biochemistry, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 02-096 Warsaw, Poland.

Publication date: January 1, 2014

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