Activation of protein kinase C by elevation of glucose concentration: Proposal for a mechanism in the development of diabetic vascular complications

Journal Article · Sat Jul 01 00:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.13.5141· OSTI ID:5228242

Lee, Tianshing; Saltsman, K A; Ohashi, Hiromi; King, G L ^[1]

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1. Harvard Medical School, Boston, MA (USA)

Hyperglycemia is believed to be the major cause of diabetic vascular complications involving both microvessels and arteries as in the retina, renal glomeruli, and aorta. It is unclear by which mechanism hyperglycemia is altering the metabolism and functions of vascular cells, although changes in nonenzymatic protein glycosylation and increases in cellular sorbitol levels have been postulated to be involved. Previously, the authors have reported that the elevation of extracellular glucose levels with cultured bovine retinal capillary endothelial cells causes an increase in protein kinase C (PKC) activity of the membranous pool with a parallel decrease in the cytosol without alteration of its total activity. Now they demonstrate that the mechanism for the activation of PKC is due to an enhanced de novo synthesis of diacylglycerol as indicated by a 2-fold increase of ({sup 14}C)diacylglycerol labeling from ({sup 14}C)glucose. The elevated diacylglycerol de novo synthesis is secondarily due to increased formation of precursors derived from glucose metabolism; this formation is enhanced by hyperglycemia as substantiated by elevated ({sup 3}H)glucose conversion into water. This effect of hyperglycemia on PKC is also observed in cultured aortic smooth muscle and endothelial cells and the retina and kidney of diabetic rats, but not in the brain. Since PKC in vascular cells has been shown to modulate hormone receptor turnover, neovascularization in vitro, and cell growth, they propose that this mechanism of enhancing the membranous PKC activities by hyperglycemia plays an important role in the development of diabetic vascular complications.

• OSTI ID: 5228242
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:13; ISSN 0027-8424
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
GLUCOSE
BIOLOGICAL EFFECTS
METABOLIC DISEASES
PATHOGENESIS
PHOSPHOTRANSFERASES
ENZYME INDUCTION
TRITIUM COMPOUNDS
UPTAKE
ATP
BRAIN
CARBON 14 COMPOUNDS
CATTLE
ENDOTHELIUM
GLYCEROL
PHOSPHORUS 32
PURIFICATION
RATS
RETINA
ALCOHOLS
ALDEHYDES
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
BODY AREAS
CARBOHYDRATES
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
DISEASES
DOMESTIC ANIMALS
ENZYMES
EYES
FACE
GENE REGULATION
HEAD
HEXOSES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MONOSACCHARIDES
NERVOUS SYSTEM
NUCLEI
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
RADIOISOTOPES
RODENTS
RUMINANTS
SACCHARIDES
SENSE ORGANS
TISSUES
TRANSFERASES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques