ArticleThe Journal of clinical investigation1997
Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats.
Article in The Journal of clinical investigation, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 1 of them a synthesis that pooled it.
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Who cites it
123 citing papers in PubMed, 1 synthesis or guideline pooled it, 537 citations in OpenAlex.
- Autophagy as a therapeutic target in diabetic nephropathy.Experimental diabetes research · 2012Pooled it
- Renoprotective effects of clarithromycin via reduction of urinary MCP-1 levels in type 2 diabetic patients.Clinical and experimental nephrology · 2011Trial
- Effects of chronic renal failure on the pharmacokinetics of ruboxistaurin and its active metabolite 338522.Clinical pharmacokinetics · 2006Trial
- Molecular pathways and emerging therapeutic targets in the pathogenesis of diabetic kidney disease.Frontiers in physiology · 2026Review
- Fenofibrate and Diabetic Retinopathy.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2025Review
- The role of myocardial fibrosis in the diabetic cardiomyopathy.Diabetology & metabolic syndrome · 2025Review
- Moroccan Antihypertensive Plants and their Mechanisms of Action.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Prediabetes-Associated Changes in Skeletal Muscle Function and Their Possible Links with Diabetes: A Literature Review.International journal of molecular sciences · 2023Review
- Pathomechanisms of Diabetic Kidney Disease.Journal of clinical medicine · 2023Review
- Methylglyoxal in Cardiometabolic Disorders: Routes Leading to Pathology Counterbalanced by Treatment Strategies.Molecules (Basel, Switzerland) · 2023Review
- A protein kinase C α and β inhibitor blunts hyperphagia to halt renal function decline and reduces adiposity in a rat model of obesity-driven type 2 diabetes.Scientific reports · 2023Article
- Review
- Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism.Life (Basel, Switzerland) · 2023Review
- Inhibition of angiotensin converting enzyme increases PKCβI isoform expression via activation of substance P and bradykinin receptors in cultured astrocytes of mice.Journal of veterinary science · 2023Article
- The Mechanism of Hyperglycemia-Induced Renal Cell Injury in Diabetic Nephropathy Disease: An Update.Life (Basel, Switzerland) · 2023Review
- The Role of Diacylglycerol Kinase in the Amelioration of Diabetic Nephropathy.Molecules (Basel, Switzerland) · 2022Review
- Anti-hyperalgesic effects of photobiomodulation therapy (904 nm) on streptozotocin-induced diabetic neuropathy imply MAPK pathway and calcium dynamics modulation.Scientific reports · 2022Article
- Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives.World journal of diabetes · 2022Review
- The role of protein kinase C in diabetic microvascular complications.Frontiers in endocrinology · 2022Review
- Diabetes and peripheral artery disease: A review.World journal of diabetes · 2021Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Induction of protein kinase C (PKC) pathway in the vascular tissues by hyperglycemia has been associated with many of the cellular changes observed in the complications of diabetes. Recently, we have reported that the use of a novel, orally effective specific inhibitor of PKC beta isoform (LY333531) normalized many of the early retinal and renal hemodynamics in rat models of diabetes. In the present study, we have characterized a spectrum of biochemical and molecular abnormalities associated with chronic changes induced by glucose or diabetes in the cultured mesangial cells and renal glomeruli that can be prevented by LY333531. Hyperglycemia increased diacylglycerol (DAG) level in cultured mesangial cells exposed to high concentrations of glucose and activated PKC alpha and beta1 isoforms in the renal glomeruli of diabetic rats. The addition of PKC beta selective inhibitor (LY333531) to cultured mesangial cells inhibited activated PKC activities by high glucose without lowering DAG levels and LY333531 given orally in diabetic rats specifically inhibited the activation of PKC beta1 isoform without decreasing PKC alpha isoform activation. Glucose-induced increases in arachidonic acid release, prostaglandin E2 production, and inhibition of Na+-K+ ATPase activities in the cultured mesangial cells were completely prevented by the addition of LY333531. Oral feeding of LY333531 prevented the increased mRNA expression of TGF-beta1 and extracellular matrix components such as fibronectin and alpha1(IV) collagen in the glomeruli of diabetic rats in parallel with inhibition of glomerular PKC activity. These results suggest that the activation of PKC, predominately the beta isoform by hyperglycemia in the mesangial cells and glomeruli can partly contribute to early renal dysfunctions by alteration of prostaglandin production and Na+-K+ ATPase activity as well as the chronic pathological changes by the overexpression of TGF-beta1 and extracellular matrix components genes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.