Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jun 18;8(12):e012673.
doi: 10.1161/JAHA.119.012673. Epub 2019 Jun 12.

Glucose Metabolism in Cardiac Hypertrophy and Heart Failure

Diem H Tran  1 , Zhao V Wang  1
Affiliations
Review

Glucose Metabolism in Cardiac Hypertrophy and Heart Failure

Diem H Tran et al. J Am Heart Assoc. .
No abstract available

Keywords: glucose metabolism; heart failure; ischemic heart disease; pathological cardiac remodeling.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Glucose metabolic pathways in the heart. In cardiomyocytes, glucose is transported through glucose transporters GLUT1 or GLUT4. Polyol pathway‐derived sorbitol and fructose may be converted to AGEs or fructose 6‐P for glycolytic use. Intracellular glucose can be phosphorylated to glucose 6‐phosphate by hexokinase (HK). Glucose 6‐phosphate is then metabolized bv multiple pathways, including glycolysis, pentose phosphate pathway (PPP), and hexosamine biosynthetic pathway (HBP). In the cytosol, pyruvate can be utilized to form alanine or lactate. In mitochondria, pyruvate is converted to acetyl‐CoA for the tricarboxylic acid cycle. Ribulose 5‐P derived from PPP can be used for pyrimidine/purine synthesis or converted into intermediates of glycolysis. UDP‐GlcNAc, the final product of HBP, serves as a substrate for the synthesis of proteoglycans, hyaluronan, glycolipid, GPI anchor, O‐GlcNAc modification, and N‐glycan. AGEs indicates advanced glycation end products; fructose 6‐P, fructose 6‐phosphate; GLUT, glucose transporter; glyceraldehyde 3‐P, glyceraldehyde 3‐phosphate; GPI, glycosylphosphatidylinositol; O‐GlcNAc, O‐linked β‐N‐acetylglucosamine; ribulose 5‐P, ribulose 5‐phosphate; UDP‐GlcNAc, uridine diphosphate N‐acetylglucosamine.
Figure 2
Figure 2
The glycolysis pathway in the heart. A series of enzymatic reactions of glycolysis convert glucose to pyruvate, which may be reduced to lactate or further catabolized by the TCA cycle. Glycolysis‐derived ATP plays a crucial role in maintaining the contractile function of the heart. The green arrow indicates activation of PFK1 by fructose 2,6‐biphosphate. ALT indicates alanine transaminase; fructose 1,6‐BP, fructose 1,6‐bisphosphate; fructose 2,6‐BP, fructose 2,6‐bisphosphate; fructose 6‐P, fructose 6‐phosphate; GAPDH, glyceraldehyde 3‐phosphate dehydrogenase; GLUT, glucose transporter; glyceraldehyde 3‐P, glyceraldehyde 3‐phosphate; HK, hexokinase; LDH, lactate dehydrogenase; PDH, pyruvate dehydrogenase; PFK, phosphofructokinase; PK, pyruvate kinase; TCA, tricarboxylic acid.
Figure 3
Figure 3
The polyol pathway in the heart. In the polyol pathway, aldose reductase (AR) converts glucose to sorbitol, which is subsequently oxidized to fructose by sorbitol dehydrogenase (SDH). AR also acts as an antioxidant enzyme by catalyzing toxic aldehyde to nontoxic alcohol. AGEs indicates advanced glycation end products; fructose 6‐P, fructose 6‐phosphate; GAPDH, glyceraldehyde 3‐phosphate dehydrogenase; GLUT, glucose transporter; GR, glutathione reductase; GSH, reduced glutathione; GSSG, oxidized glutathione; ROS, reactive oxygen species.
Figure 4
Figure 4
The pentose phosphate pathway in the heart. The oxidative phase of the pentose phosphate pathway (PPP) generates NADPH and ribulose 5‐phoshpate (ribulose 5‐P), which are mainly used for anabolism. The nonoxidative phase of PPP stimulates the interconversion of 5‐carbon sugars with a series of reversible reactions. Whereas acute activation of the PPP confers cardioprotection against oxidative stress, persistent upregulation of the PPP may exacerbate oxidative damage and contribute to cardiomyopathies. 6GPD indicates 6‐phosphogluconate dehydrogenase; fructose 6‐P, fructose 6‐phosphate; G6PD, glucose 6‐phosphate dehydrogenase; GLUT, glucose transporter; glyceraldehyde 3‐P, glyceraldehyde 3‐phosphate; HK, hexokinase; ribose 5‐P, ribose 5‐phosphate; xylulose 5‐P, xylulose 5‐phosphate.
Figure 5
Figure 5
The hexosamine biosynthetic pathway (HBP) in the heart. The rate‐limiting enzyme of the HBP, GFAT, converts fructose 6‐P and glutamine to glucosamine 6‐phosphate, which is used to generate the final product, UDP‐GlcNAc. UDP‐GlcNAc is a substrate for various biosynthetic pathways, including glycan synthesis, glycerolipid production, etc. UDP‐GlcNAc is also used for a prominent posttranslational protein modification on Ser/Thr sites by O‐GlcNAc transferase (OGT), which is counteracted by O‐GlcNAcase (OGA) to catalyze the removal of O‐GlcNAc. GFAT indicates glutamine:fructose 6‐phosphate amidotransferase; GLUT, glucose transporter; HK, hexokinase; UDP‐GlcNAc, uridine diphosphate N‐acetylglucosamine.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson JF, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, Mackey JS, Matchar DB, Matsushita K, Mussolino ME, Nasir K, O'Flaherty M, Palaniappan LP, Pandey A, Pandey DK, Reeves MJ, Ritchey MD, Rodriguez CJ, Roth GA, Rosamond WD, Sampson UKA, Satou GM, Shah SH, Spartano NL, Tirschwell DL, Tsao CW, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2018 update: a report from the American Heart Association. Circulation. 2018;137:e67–e492. - PubMed
    1. Braunwald E. Shattuck lecture–cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med. 1997;337:1360–1369. - PubMed
    1. Drazner MH. The progression of hypertensive heart disease. Circulation. 2011;123:327–334. - PubMed
    1. Heineke J, Molkentin JD. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol. 2006;7:589–600. - PubMed
    1. Ashrafian H, Frenneaux MP, Opie LH. Metabolic mechanisms in heart failure. Circulation. 2007;116:434–448. - PubMed

Publication types