1994
DOI: 10.2337/diab.43.9.1122
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Characterization of the Mechanism for the Chronic Activation of Diacylglycerol-Protein Kinase C Pathway in Diabetes and Hypergalactosemia

Abstract: Similar vascular pathological conditions are observed in diabetic animals and those with diet-induced hypergalactosemia. Both diabetes and hypergalactosemia are believed to cause vascular dysfunction via a common biochemical mechanism. In this study, we have found that both diabetes and hypergalactosemia in the short term (2-4 months) can increase total diacylglycerol (DAG) levels by 52 +/- 9 and 74 +/- 13% in the retina and aorta, respectively, of diabetic dogs, and by 94 +/- 9 and 78 +/- 11% in the retina an… Show more

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Cited by 370 publications
(166 citation statements)
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“…PKC activation can lead to mitogen-activated protein kinase (MAPK) activation and phosphorylation of several important transcription factors that increase gene expressions of various stress related genes like c-Jun kinases and heat shock proteins [63]. PKC-b has been shown to have a role in the form of a signaling component for VEGF and a regulator of endothelial cell permeability [64]. Furthermore, PKC activation contributes to the overexpression of plasminogen activator-1 (PAI-1), the activation of NADPH oxidase, and the activation of NFkB in many vascular cells including endothelial cells, smooth muscle cells, pericytes, mesangial cells, and others [65].…”
Section: Pkc Pathwaymentioning
confidence: 99%
“…PKC activation can lead to mitogen-activated protein kinase (MAPK) activation and phosphorylation of several important transcription factors that increase gene expressions of various stress related genes like c-Jun kinases and heat shock proteins [63]. PKC-b has been shown to have a role in the form of a signaling component for VEGF and a regulator of endothelial cell permeability [64]. Furthermore, PKC activation contributes to the overexpression of plasminogen activator-1 (PAI-1), the activation of NADPH oxidase, and the activation of NFkB in many vascular cells including endothelial cells, smooth muscle cells, pericytes, mesangial cells, and others [65].…”
Section: Pkc Pathwaymentioning
confidence: 99%
“…The induction appears to be restricted to a few "diabetes-related" isoforms in a tissue-specific manner. PKC␤ is one of these isoforms and has been most directly linked to important aspects of hyperglycemia in vivo and in vitro (15). Interestingly, PKC␤ was one of the earliest isoforms recognized in insulin signaling and appears to play dual roles in insulin signaling (17).…”
mentioning
confidence: 99%
“…Ligand precipitation of biotinylated cell surface proteins using RAPSepharose confirmed that wild type and truncated VLDL-R were expressed in similar amounts on the cell surface. (51,52), and inhibition of hyperglycemia-induced PKC-␤II activation ameliorated the microvascular complications of diabetes in animal models (53,54). To determine whether hyperglycemia induced VLDL-R phosphorylation, we incubated human dermal microvascular endothelial cells for 6 h in the following: 1) control media containing 5.5 mM D-glucose, 2) high glucose medium containing 16.5 mM D-glucose, 3) high galactose medium, identical to high glucose medium except for substitution of galactose (16.5 mM) for glucose, and 4) high mannitol medium in which the inert sugar, mannitol (16.5 mM), was substituted for glucose or galactose.…”
Section: Assessment Of the Role Of Pk-c In Regulation Of Receptor Ligmentioning
confidence: 99%
“…Culture of microvascular endothelial cells in the presence of high glucose or galactose stimulates the activation of PK-C by inducing de novo synthesis of diacylglycerol (51,64). Treatment of diabetic rats with a specific PK-C ␤II inhibitor inhibits the development of vascular dysfunction that leads to retinal, renal, and neurologic disease (53,54,65).…”
Section: Activation Of Pk-c By Elevated Glucose Concentrations Leads mentioning
confidence: 99%