May 11, 2017

EETs contribute to insulin sensitivity

Interventions that increase circulating levels of compounds called EETs may improve insulin sensitivity and treat hypertension.

Obesity, hypertension and type 2 diabetes are associated with insulin resistance and vascular dysfunction, but causal factors for these associations remain unclear.

Ambra Pozzi, Ph.D., James Luther, M.D., MSCI, and colleagues explored a role for endogenous EETs – products of the enzyme CYP2C – in regulating insulin sensitivity.

The investigators assessed insulin sensitivity in mice missing one of the CYP2C genes and found that the mice had reduced glucose tolerance and insulin sensitivity compared to control mice. Additional findings suggested that impaired vascular reactivity produced the impaired insulin sensitivity in vivo. The investigators also found that plasma EETs in humans were positively associated with insulin sensitivity.

The findings, reported in Diabetologia, demonstrate that CYP2C-derived EETs contribute to insulin sensitivity in mice and in humans. They suggest that interventions aimed at increasing circulating EETs in humans – such as EET agonists and inhibitors of EET metabolism, which are currently in development – may improve insulin sensitivity and treat hypertension.

This research was supported by grants from the National Institutes of Health (DK095761, DK081662, DK038226, HL060906, RR024975, TR000445), the Department of Veterans Affairs and the Vanderbilt Mouse Metabolic Phenotyping Center (DK059637).

Send suggestions for articles to highlight in Aliquots and any other feedback about the column to