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- Title
Abnormalities of retinal metabolism in diabetes or experimental galactosemia: V. Relationship between protein kinase C and ATPases.
- Authors
Kowluru, Renu A.; Jirousek, Michael R.; Stramm, Lawrence; Farid, Nagy; Engerman, Ronald L.; Kern, Timothy S.; Kowluru, R A; Jirousek, M R; Stramm, L; Farid, N; Engerman, R L; Kern, T S
- Abstract
In the retinas of diabetic animals, protein kinase C (PKC) activity is elevated, and Na+-K+-ATPase and calcium ATPase activities are subnormal. These abnormalities are also present in another model of diabetic retinopathy, experimental galactosemia. We have investigated the relationship between hyperglycemia-induced abnormalities of PKC and ATPases using a selective inhibitor of beta isoform of PKC (LY333531). Diabetes or experimental galactosemia of 2 months' duration resulted in > 50% elevation of PKC activity in the retina, and administration of LY333531 prevented the elevation. In retinas of the same rats, the LY333531 prevented hyperglycemia-induced decreases of both Na+-K+-ATPase and calcium ATPase activities. Retinal microvessels, the main site of lesions in diabetic retinopathy, likewise showed elevated activity of PKC and inhibition of ATPases in diabetes and in experimental galactosemia, and administration of LY333531 to diabetic animals prevented these abnormalities. PKC activity in sciatic nerves, in contrast, became subnormal in diabetes and experimental galactosemia, and LY333531 had no effect on PKC activity in the sciatic nerve. PKC activity in the cerebral cortex was not affected by diabetes or experimental galactosemia. The results suggest that diabetes-induced reductions in Na+-K+-ATPase and calcium ATPase in the retina are mediated in large part by PKC-beta. The availability of an agent that can normalize the hyperglycemia-induced increase in PKC activity in the retina should facilitate investigation of the role of PKC in the development of diabetic retinopathy.
- Subjects
PROTEIN kinase C; HYPERGLYCEMIA; DIABETES; RETINA; CHEMICAL inhibitors; ADENOSINE triphosphatase; ANIMAL experimentation; CEREBRAL cortex; COMPARATIVE studies; ENZYME inhibitors; GALACTOSEMIA; INORGANIC compounds; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; RATS; RESEARCH; STATISTICAL sampling; SCIATIC nerve; TRANSFERASES; EVALUATION research; INDOLE compounds; PHARMACODYNAMICS
- Publication
Diabetes, 1998, Vol 47, Issue 3, p464
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.47.3.464