Article

Functional coupling of angiotensin II type 1 receptor with insulin resistance of energy substrate uptakes in immortalized cardiomyocytes (HL-1 cells).

Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy.
British Journal of Pharmacology (impact factor: 4.41). 04/2008; 153(5):907-14. DOI:10.1038/sj.bjp.0707563 pp.907-14
Source: PubMed

ABSTRACT Increased angiotensin II levels and insulin resistance coexist at the early stages of cardiomyopathies. To determine whether angiotensin II increases insulin resistance in cardiomyocytes, we studied the effect of angiotensin II on basal and insulin-stimulated transport rate of energy substrates in immortalized cardiomyocytes (HL-1 cells).
Glucose and palmitic acid uptakes were measured using [(3)H]2-deoxy-D-glucose and [(14)C]palmitic acid, respectively, in cells exposed or not exposed to angiotensin II (100 nM), angiotensin II plus irbesartan or PD123319, type 1 and 2 receptor antagonists, or PD98059, an inhibitor of ERK1/2 activation. Cell viability, DNA, protein synthesis and surface area were evaluated by the MTT test, [(3)H]thymydine, [(3)H]leucine and morphometric analysis, respectively. Type 1 receptor levels were measured by western blot analysis.
Basal uptakes of glucose and palmitic acid by HL-1 cells (0.37+/-0.07 and 7.31+/-0.22 pmol per 10(4)cells per min, respectively) were both stimulated by 100 nM insulin (+91 and +64%, respectively). Cells exposed to angiotensin II remained viable and did not show signs of hypertrophy. In these conditions, the basal palmitic acid uptake of the cells increased (11.41+/-0.46 pmol per 10(4) cells per min) and insulin failed to stimulate the uptake of glucose and fatty acids. Changes in the rate of uptake of energy substrates were prevented or significantly reduced by irbesartan or PD98059.
Angiotensin II is a candidate for increasing insulin resistance in cardiomyocytes. Our results suggest a further mechanism for the cardiovascular protection offered by the angiotensin II type 1 receptor blockers.

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Keywords

100 nM insulin
 
2 receptor antagonists
 
angiotensin II increases insulin resistance
 
angiotensin II type 1 receptor blockers
 
basal palmitic acid uptake
 
Basal uptakes
 
Cell viability
 
ERK1/2 activation
 
fatty acids
 
immortalized cardiomyocytes
 
Increased angiotensin II levels
 
insulin resistance coexist
 
insulin-stimulated transport rate
 
morphometric analysis
 
palmitic acid uptakes
 
protein synthesis
 
surface area
 
type 1
 
Type 1 receptor levels
 
western blot analysis