Insulin receptor substrate signaling controls cardiac energy metabolism and heart failure - PubMed (original) (raw)

Figure 1.

Metabolic flexibility of cardiomyocyte in use of glucose, fatty acids, lactate, amino acids, ketone bodies for generation of ATP to support cardiac contractile function. Insulin stimulates anabolic metabolism, including glucose uptake, glycolysis, and synthesis of glycogen, ribonucleotide, and lipid synthesis, while insulin inhibits the β-oxidation of fatty acids. An excess amount of ATP can be stored in creatine phosphate, and activated pentose phosphate pathway promotes synthesis of macromolecules and cardiac hypertrophy. Hexosamine biosynthetic pathway promotes glycosylation of many cellular proteins and bioactivity of target proteins and biological responses, particularly under hyperglycemia or insulin resistance. G-6-P-glucose-6-phosphate, G-1-P-gluocse-1-phosphate, F-6-P-fructose-6-phosphate, F-1,6-BP-fructose-1.2,-biphosphate, F2,6-BP-fructoase-2,6-biphosphate, PFK1-phosphofructokinase-1, PFK2-phosphofructokinase-2, NADPH-nicotinamide adenine dinucleotide phosphate, AR-aldose reductase, GFA-glutamine fructose-6-phosphate aminotransferase, PEP-phosphoenolpyruvate, MPC-mitochondrial pyruvate carrier, TCA-tricarboxylic acid, PPP-pentose phosphate pathway, G6PD-glucose-6-phosphate dehydrogenase, Gck-glucokinase, Glut- glucose transporter, HBP-hexosamine biosynthetic pathway, CTP1-carnitine-palmitoyltransferase-1, PDK4-pyruvate dehydrogenase kinase-4, PDH-pyruvate dehydrogenase, Ox phos-oxidative phosphorylation, β-oxidation-fatty acid beta-oxidation, NADH-nicotinamide adenine dinucleotide, DGAT-diacylglycerol O-acyltransferase, ATGL-adipose triglyceride lipase, Fasn-fatty acid synthase, TAG-triglycerides. ACC- Acetyl-CoA carboxylase, PC-pyruvate carboxylase, CK-Creatine kinase, Creatine-P- Creatine phosphate.