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High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
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Published on: January 23, 2018

Selective PKC beta inhibition with ruboxistaurin and endothelial function in type-2 diabetes mellitus

Nehal N Mehta1, Matthew Sheetz, Karen Price

  • 1Cardiovascular Institute, University of Pennsylvania Medical Center, 909 BRB 2/3, 421 Curie Blvd., Philadelphia, PA 19104-6160, USA.

Cardiovascular Drugs and Therapy
|October 25, 2008
PubMed
Abstract

Insights

This study suggests that inhibiting protein kinase C beta (PKC beta) may improve blood vessel function in type-2 diabetes. Further research is needed to confirm if PKC beta inhibition can reduce cardiovascular disease risk.

Area of Science:

  • Cardiovascular Research
  • Endocrinology
  • Pharmacology

Background:

  • Type-2 diabetes mellitus significantly elevates the risk of atherosclerotic cardiovascular disease.
  • The precise mechanisms linking hyperglycemia to atherosclerosis are not fully understood.
  • Endothelial dysfunction, potentially mediated by protein kinase C beta (PKC beta) activation, is a proposed link.

Purpose of the Study:

  • To investigate the effect of a PKC beta-specific inhibitor, ruboxistaurin, on macrovascular endothelial function in patients with type-2 diabetes.
  • To assess changes in brachial artery flow-mediated dilation (FMD) and urinary isoprostanes as indicators of endothelial function and oxidative stress.

Main Methods:

  • A double-masked, placebo-controlled trial was conducted.
  • Participants with type-2 diabetes received either ruboxistaurin (32 mg/day) or a placebo for 6 weeks.
  • Ultrasound-assessed brachial artery FMD and urinary isoprostanes were measured.

Main Results:

  • Ruboxistaurin showed a trend towards improving FMD at 1 and 5 minutes post-cuff deflation compared to placebo (p=0.08 and p=0.02, respectively).
  • No significant effect was observed on nitroglycerin-mediated dilation.
  • Urinary isoprostane levels, an indicator of oxidant stress, were not affected by ruboxistaurin.

Conclusions:

  • This proof-of-concept study is the first to indicate that specific inhibition of PKC beta may enhance macrovascular endothelial function in type-2 diabetes.
  • Larger clinical trials are necessary to evaluate the efficacy of PKC beta inhibition in preventing atherosclerotic cardiovascular complications associated with diabetes.

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