Protein kinase C is activated in glomeruli from streptozotocin diabetic rats: possible mediation by glucose

• Published in: The Journal of clinical investigation Vol. 83; no. 5; pp. 1667 - 1675
• Main Authors: CRAVEN, P. A, DERUBERTIS, F. R
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01-05-1989
• Subjects: Animals; Biological and medical sciences; diabetes mellitus; Diabetes Mellitus, Experimental - enzymology; Diabetes Mellitus, Experimental - metabolism; Diabetes. Impaired glucose tolerance; Diglycerides - biosynthesis; Diglycerides - metabolism; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme Activation; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; glomerulus; Glucose - pharmacology; Inositol - metabolism; kidney; Kidney Glomerulus - enzymology; Kidney Glomerulus - metabolism; Medical sciences; Phospholipids - metabolism; Phosphorus Radioisotopes - metabolism; protein kinase C; Protein Kinase C - metabolism; Rats; Rats, Inbred Strains; Subcellular Fractions - enzymology; Endocrinopathy; Protein kinase C; Statistical analysis; Radiolabelling; Rat; Enzyme; Diabetes mellitus; Rodentia; Inositol phosphate; Kidney; Ion exchange chromatography; Thin layer chromatography; Vertebrata; Mammalia; Enzymatic activity; Metabolic activation; Glomerulus
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci114066

Glomerular inositol content and the turnover of polyphosphoinositides was reduced by 58% in 1-2 wk streptozotocin diabetic rats. Addition of inositol to the incubation medium increased polyphosphoinositide turnover in glomeruli from diabetic rats to control values. Despite the reduction in inositol content and polyphosphoinositide turnover, protein kinase C was activated in glomeruli from diabetic rats, as assessed by an increase in the percentage of enzyme activity associated with the particulate cell fraction. Total protein kinase C activity was not different between glomeruli from control and diabetic rats. Treatment of diabetic rats with insulin to achieve near euglycemia prevented the increase in particulate protein kinase C. Moreover, incubation of glomeruli from control rats with glucose (100-1,000 mg/dl) resulted in a progressive increase in labeled diacylglycerol production and in the percentage of protein kinase C activity which was associated with the particulate fraction. These results support a role for hyperglycemia per se in the enhanced state of activation of protein kinase C seen in glomeruli from diabetic rats. Glucose did not appear to increase diacylglycerol by stimulating inositol phospholipid hydrolysis in glomeruli. Other pathways for diacylglycerol production, including de novo synthesis and phospholipase C mediated hydrolysis of phosphatidylcholine or phosphatidyl-inositol-glycan are not excluded.