title: Differential activations of PKC/PKA related to microvasculopathy in diabetic GK rats.
abstract: Microvasculopathy is the most serious and predictable threat to the health of diabetic patients, which often results in end-stage renal disease, blindness, and limb amputations. Up to the present, the underlying mechanisms have remained elusive. Here, it was found that the differential activations of PKC/PKA were involved in diabetic microvasculopathy in diabetic GK rats. By real-time PCR, Western blot, immunohistochemistry, and enzyme activity assay, upregulation of PKC was prominent in kidney but was not significant in liver and brain. The expression and activity of PKA were lowered in kidney but comparable in brain and liver during diabetic nephropathy. Furthermore, the generation of reactive oxygen species, production of nitric oxide, and expression of inducible nitric oxide synthase induced by advanced glycation end products were inhibited by PKCβ inhibitor LY-333531 or a PKA agonist in rat glomerular microvascular endothelial cells. Finally, albuminuria was significantly lowered by a PKA agonist and boosted by a PKA antagonist. It suggested that the differential activations of PKC/PKA related to microvasculopathy in diabetes and that activation of PKA may protect the diabetic microvasculature.
authors: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
authors: Hui
authors: H
authors: Wang
authors: Yong-Wei
authors: YW
authors: Jiang
authors: Wen-Jian
authors: WJ
authors: Zhang
authors: Shi-Qing
authors: SQ
authors: Xu
authors: Hong-Lin
authors: HL
authors: Liu
authors: Wen-Ying
authors: WY
authors: Yang
authors: Jin-Ning
authors: JN
authors: Lou
mesh_terms: D000419:Albuminuria / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology; D008099:Liver / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
chemical_list: D017127:Glycation End Products, Advanced; D052247:Nitric Oxide Synthase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C