Metabolic switch and hypertrophy of cardiomyocytes following treatment with angiotensin II are prevented by AMP-activated protein kinase.

Stuck BJ, Lenski M, Böhm M, Laufs U

The Journal of biological chemistry12 Sept 2008Cited by 104 (Europe PMC)

PMID18790741DOI10.1074/jbc.m801904200PepBankPUB-18790741

Summary

Angiotensin II induces cardiomyocyte hypertrophy, but its consequences on cardiomyocyte metabolism and energy supply are not completely understood. Here we investigate the effect of angiotensin II on glucose and fatty acid utilization and the modifying role of AMP-activated protein kinase (AMPK), a key regulator of metabolism and proliferation. Treatment of H9C2 cardiomyocytes with angiotensin II (Ang II, 1 microm, 4 h) increased [(3)H]leucine incorporation, up-regulated the mRNA expression of the hypertrophy marker genes MLC, ANF, BNP, and beta-MHC, and decreased the phosphorylation of the negative mTOR-regulator tuberin (TSC-2). Rat neonatal cardiomyocytes showed similar results. Western blot analysis revealed a time- and concentration-dependent down-regulation of AMPK-phosphorylation in the presence of angiotensin II, whereas the protein expression of the catalytic alpha-subunit remained unchanged. This was paralleled by membrane translocation of glucose-transporter type 4 (GLUT4), increased uptake of [(3)H]glucose and transient down-regulation of phosphorylation of acetyl-CoA carboxylase (ACC), whereas fatty acid uptake remained unchanged. Similarly, short-term transaortic constriction in mice resulted in down-regulation of P-AMPK and P-ACC but up-regulation of GLUT4 membrane translocation in the heart. Preincubation of cardiomyocytes with the AMPK stimulator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 1 mM, 4 h) completely prevented the angiotensin II-induced cardiomyocytes hypertrophy. In addition, AICAR reversed the metabolic effects of angiotensin II: GLUT4 translocation was reduced, but ACC phosphorylation and TSC phosphorylation were elevated. In summary, angiotensin II-induced hypertrophy of cardiomyocytes is accompanied by decreased activation of AMPK, increased glucose uptake, and decreased mTOR inhibition. Stimulation with the AMPK activator AICAR reverses these metabolic changes, increases fatty acid utilization, and inhibits cardiomyocyte hypertrophy.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Mechanism
In cardiomyocytes, AICAR preincubation completely prevented angiotensin II-induced hypertrophy.
In plain wordsIn cells, AICAR prevented enlargement caused by angiotensin II compared with angiotensin II alone.
Peptide
AICAR (acadesine)
Outcome
DecreaseCardiomyocyte hypertrophy
Study
ratn: not reported in source
Cardiomyocytes
Comparator
Angiotensin II alone
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
1 mM · 4 hAs given in this study (rat).
Source sentences
Summary
Preincubation of cardiomyocytes with the AMPK stimulator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 1 mM, 4 h) completely prevented the angiotensin II-induced cardiomyocytes hypertrophy.
Show in the study text Report a problemFND-1879074101
02LabIn vitro (cells)Mechanism
In cardiomyocytes, AICAR reduced GLUT4 translocation induced by angiotensin II.
In plain wordsIn cells, AICAR reduced GLUT4 movement compared with angiotensin II alone.
Peptide
AICAR (acadesine)
Outcome
DecreaseGLUT4 translocation
Study
ratn: not reported in source
Cardiomyocytes
Comparator
Angiotensin II alone
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
1 mM · 4 hAs given in this study (rat).
Source sentences
Summary
In addition, AICAR reversed the metabolic effects of angiotensin II: GLUT4 translocation was reduced, but ACC phosphorylation and TSC phosphorylation were elevated.
Show in the study text Report a problemFND-1879074102
03LabIn vitro (cells)Mechanism
In cardiomyocytes, AICAR elevated ACC phosphorylation relative to angiotensin II alone.
In plain wordsIn cells, AICAR increased ACC phosphorylation compared with angiotensin II alone.
Peptide
AICAR (acadesine)
Outcome
IncreaseACC phosphorylation
Study
ratn: not reported in source
Cardiomyocytes
Comparator
Angiotensin II alone
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
1 mM · 4 hAs given in this study (rat).
Source sentences
Summary
In addition, AICAR reversed the metabolic effects of angiotensin II: GLUT4 translocation was reduced, but ACC phosphorylation and TSC phosphorylation were elevated.
Show in the study text Report a problemFND-1879074103
04LabIn vitro (cells)Mechanism
In cardiomyocytes, AICAR elevated TSC phosphorylation relative to angiotensin II alone.
In plain wordsIn cells, AICAR increased TSC phosphorylation compared with angiotensin II alone.
Peptide
AICAR (acadesine)
Outcome
IncreaseTSC phosphorylation
Study
ratn: not reported in source
Cardiomyocytes
Comparator
Angiotensin II alone
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
1 mM · 4 hAs given in this study (rat).
Source sentences
Summary
In addition, AICAR reversed the metabolic effects of angiotensin II: GLUT4 translocation was reduced, but ACC phosphorylation and TSC phosphorylation were elevated.
Show in the study text Report a problemFND-1879074104

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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