Protein kinase C is activated in glomeruli from streptozotocin diabetic rats. Possible mediation by glucose
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.
- Research Organization:
- Veterans Administration Medical Center, Pittsburgh, PA (USA)
- OSTI ID:
- 5902552
- Journal Information:
- J. Clin. Invest.; (United States), Vol. 83:5
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DIABETES MELLITUS
PATHOGENESIS
GLUCOSE
BIOCHEMICAL REACTION KINETICS
PHOSPHOLIPIDS
METABOLISM
PHOSPHOTRANSFERASES
ENZYME ACTIVITY
BIOLOGICAL PATHWAYS
INOSITOL
INSULIN
KIDNEYS
PHOSPHORUS ISOTOPES
RATS
TRACER TECHNIQUES
ALDEHYDES
ANIMALS
BODY
CARBOHYDRATES
DISEASES
ENDOCRINE DISEASES
ENZYMES
ESTERS
HEXOSES
HORMONES
INOSITOLS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIPIDS
MAMMALS
METABOLIC DISEASES
MONOSACCHARIDES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PEPTIDE HORMONES
PHOSPHORUS-GROUP TRANSFERASES
REACTION KINETICS
RODENTS
SACCHARIDES
TRANSFERASES
VERTEBRATES
550901* - Pathology- Tracer Techniques