Role of glucose metabolism in amelogenesis

Cell energy metabolism plays a pivotal role in organ development and function by regulating cell behavior in pathophysiological conditions. Glucose metabolism is the central cascade for obtaining energy in mammalian cells, and cells alter the glucose metabolic pathway depending on intra- and extracellular environments. Therefore, glucose metabolism is closely associated with cell differentiation stages, and cell energy metabolism plays a vital role not only in energy production but also in cell fate regulation in organogenesis.

During enamel formation, the timing of the expression of passive and active glucose transporters, glycogen synthesis, and glycogen degradation is strictly regulated according to the energy demand of ameloblast-lineage cells. These glucose metabolic reactions are particularly active in the maturation stage of ameloblasts. Furthermore, autophagy, a key regulator of cellular energy homeostasis that modulates glucose metabolism, occurs during both the secretory and maturation stages of ameloblasts. Disruption of glucose metabolism cascade and autophagy induces enamel hypoplasia, as demonstrated in both in vitro and in vivo models.

Adequate energy supply via glucose metabolism is essential for enamel matrix secretion and maturation. A thorough understanding of the precise regulation of energy metabolism in amelogenesis facilitates comprehension of the normal enamel formation process and pathological conditions affecting it. This review summarizes glucose metabolic processes during amelogenesis, focusing on glucose uptake, glycogenesis, and glycogenolysis.