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

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.

journal_name

Med Hypotheses

journal_title

Medical hypotheses

authors

McCarty MF

doi

10.1016/j.mehy.2004.01.042

keywords:

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

1211-5

issue

6

eissn

0306-9877

issn

1532-2777

pii

S0306987704002956

journal_volume

64

pub_type

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