Format

Send to

Choose Destination
See comment in PubMed Commons below
Med Hypotheses. 2005;64(6):1211-5.

AMPK activation as a strategy for reversing the endothelial lipotoxicity underlying the increased vascular risk associated with insulin resistance syndrome.

Author information

1
NutriGuard Research, 1051 Hermes Avenue, Encinitas, CA 92024, USA. mccarty@pantox.com

Abstract

The endotheliopathy associated with insulin resistance syndrome appears to result largely from excessive free fatty acid (FFA) exposure that boosts endothelial production of diacylglycerol, thereby activating protein kinase C. This endothelial "lipotoxicity" can be alleviated by very-low-fat diets and by appropriate weight loss. In addition, pharmacological activation of endothelial AMP-activated kinase (AMPK), as with the drug metformin, has the potential to decrease the FFA content of endothelial cells by stimulating fat oxidation; AMPK may also suppress endothelial de novo synthesis of diacylglycerol by inhibiting glycerol-3-phosphate acyltransferase. These considerations may rationalize the superior impact of metformin therapy on the macrovascular health of diabetics. More generally, metformin - or, preferably, better tolerated activators of AMPK - may have considerable potential for promoting vascular health in the large proportion of the adult population afflicted with insulin resistance syndrome.

PMID:
15823720
DOI:
10.1016/j.mehy.2004.01.042
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center