During the digestive phase, glucose utilization is regulated to ensure that blood glucose levels are maintained within a specific range. The transporters responsible for glucose uptake in different cell types include GLUT1, GLUT2, GLUT3, and functional GLUT4 localized on the cell membrane. Various metabolic reactions and pathways are involved, such as hexokinase/glucokinase, glycolysis, lactate dehydrogenase, TCA cycle, oxidative phosphorylation, glycogen synthesis, de novo lipogenesis, and esterification of free fatty acids (FFA) to form triglycerides (TG).

In the fasting phase, energy metabolism undergoes certain changes. GLUT4 becomes inactive and is localized intracellularly. In addition to the metabolic reactions and pathways mentioned earlier, other processes like glycogenolysis, gluconeogenesis, G6Pase activity, ketogenesis, proteolysis, β-oxidation, and ketolysis contribute to the production and utilization of various metabolites such as amino acids (AAs), free fatty acids (FFA), glycerol (G’OL), ketone bodies (KBs), lactate (LACT), and protein (PROT).

Maintaining blood glucose levels within specific limits is crucial for the proper functioning of cells. Glucose levels need to be above 60 mg/dL to prevent hypoglycemia, while avoiding levels above 100 mg/dL during fasting to prevent detrimental glucose-induced reactions and osmotic imbalances that can damage cell function.
RBCCNSDietG6PG6P GLY HEPATOADIPOSKM2,4,5 11 2,3 2,4,5 8 7,82,4,52,3,4,5 6 G6P G6P G3G1 1 1 1 G2 G4-mG4-mG4-m ATP A. Digestive Phase ATP ATP TG G’OL3P G6P TG GlucoseATP 6 ATP GLY ATP G6P AAs G’OL ATP ATP13 TG 11 11 12 12 FFA A,4,5 GLY ATP RBCSKMG6P KBs CNS2,4,5112 3 HEPATOFFA 9 11 10 KBs A,4,5 A,4,5 B,4,5 G4-iG4-i B,4,5 ADIPOB,4,5 GLY G6P LACT ATP G6P Glucose PROT G4-iG4-i G1G1 G3G3 G2G2 B. Fasting Phase •Fig. 39.3 A, Overview of glucose utilization during the digestive phase. GLUTtransporters:G1,GLUT1;G2,GLUT2;G3,GLUT3;G4-m,functionalGLUT4localizedtocellmembrane.Celltypes:ADIPO,adipocyte;CNS,centralnervoussystemneuronsandglia;HEPATO,hepatocyte;RBC,redbloodcell;SKM,skeletalmyocyte.Metabolites:G6P,glucose-6-phosphate;GLY,glycogen;G’OL3P,glycerol-3-phosphate;TG,triglyceride.Metabolicreactions/pathways:1,hexokinase/glucokinase;2,glycolysis;3,lactatedehydrogenase;4,TCAcycle± pyruvatedehydrogenase;5,oxidativephosphorylation;6,glycogensynthesis;7,denovolipogenesis;8,esterificationofFFAstoG’OL3PtoformTG.B, Overview of energy metabolism during the fasting phase. GLUTtransporters:seelegendforA,plus:G4-I,inactiveGLUT4withintracellularlocalization.Celltypes:seelegendforAMetabolites:seelegendforA,plus:AAs,aminoacids;FFA,freefattyacid;G’OL,glycerol;KBs,ketonebodies;LACT,lactate;PROT,protein.Metabolicreactions/pathways:seelegendforA,plus:9,glycogenolysis;10,gluconeogenesis;11,G6Pase;12,ketogenesis;13,proteolysis;A,β-oxidation;B,ketolysis.
and death) can occur. This means that whole-body metabolism during the interdigestive and fasting phases must meet the challenge of maintaining blood glucose above 60 mg/ dL (see
Fig. 39.2 , green arrow).
On the other hand, glucose levels must be maintained below a certain maximal threshold (i.e., fasting blood glucose < 100 mg/dL) to avoid glucose-induced side reactions (both enzymatic and nonenzymatic) as well as osmotic imbalances that lead to multiple forms of damage to cell function (see
Fig. 39.2 , red arrow).