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PMID: 2708528 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Protein kinase C is activated in glomeruli from streptozotocin diabetic rats. Possible mediation by glucose.

The Journal of clinical investigation ·Vol. 83 ·No. 5 ·1989-05-00 ·Pages 1667-75

Craven PA, DeRubertis FR

Abstract

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.

MeSH Terms
Animals Diabetes Mellitus, Experimental/enzymology,metabolism Diglycerides/biosynthesis,metabolism Enzyme Activation Female Glucose/pharmacology Inositol/metabolism Kidney Glomerulus/enzymology,metabolism Phospholipids/metabolism Phosphorus Radioisotopes/metabolism Protein Kinase C/metabolism Rats Rats, Inbred Strains Subcellular Fractions/enzymology
Chemicals
Diglycerides Phospholipids Phosphorus Radioisotopes Inositol Protein Kinase C Glucose
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Craven P A
Department of Medicine, Veterans Administration Medical Center, Pittsburgh, Pennsylvania 15240.
DeRubertis F R
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI114066
Published
1989-05-00
Pages
1667-75
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC303875
Subset
IM
Grants
NIDDK NIH HHS · 5-R01-DK 34592 · United States
External Links
PubMed source DOI: 10.1172/JCI114066 PMC Full Text View journal details
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