Increased expression of liver PKC α in hypoinsulinemic diabetic rats: a post-translational effect

• Published in: Molecular and cellular endocrinology 1998-11, Vol.146 (1), p.177-185
• Main Authors: Nivet, V, Antoine, P.J, Amessou, M, Descamps, G, Desbuquois, B, Clot, J.P, Durand, D
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - metabolism; Cell Nucleus - enzymology; Cytosol - enzymology; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - enzymology; Diabetic rats; Gene Expression; Insulin; Insulin - blood; Insulin - pharmacology; Isoenzymes - analysis; Isoenzymes - genetics; Liver - enzymology; Liver - ultrastructure; Liver subcellular fractions; Male; Microsomes, Liver - enzymology; Mitochondria, Liver - enzymology; Phlorhizin - pharmacology; Phlorizin; PKC α mRNA; Protein Kinase C - analysis; Protein Kinase C - genetics; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; STZ
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/S0303-7207(98)00155-5

Ca 2+-dependent protein kinase C (cPKC) activity and expression have been studied in livers from hypoinsulinemic streptozotocin (STZ)-induced diabetic and untreated control rats. In diabetic rats, cPKC activity was slightly decreased in liver total particulate and nuclear fractions but was unchanged in mitochondrial-lysosomal, microsomal and cytosolic fractions. On Western immunoblot analysis, PKC α was identified as two distinct proteins of 90 and 81 kDa. In diabetic rats, the abundance of the 90 kDa protein was increased in most subcellular fractions with a maximun in the cytosolic and microsomal fractions (180%) but that of the 81 kDa protein was unchanged. PKC β2 was detected as a single 81 kDa protein in cytosolic and microsomal fractions with unchanged levels in diabetic rats. Liver PKC α mRNA levels as measured by reverse transcription and competitive PCR amplification were similar in diabetic and control rats. The increased expression of PKC α protein in diabetic rats was reversed by insulin but not by phlorizin, suggesting that it did not result from hyperglycemia. We conclude that STZ-induced diabetes induces the expression of a biologically inactive form of PKC α which differs from active PKC α by an undefined post-translational modification, possibly an increase in phosphorylation state.