Glycogen shunt is essential for submandibular gland morphogenesis.

Glycogen metabolism is an important pathway in energy metabolism, and when cells require energy, glycogen is broken down into glucose-1-phosphate through glycogenolysis, which serves as an intracellular energy source. Recently, the concept of "glycogen shunt" has been proposed to regulate the synthesis, accumulation, and breakdown of glycogen to provide glucose at the appropriate time, particularly in organogenesis. This study demonstrated the timing of the localization of glycogen and molecules related to glycogen metabolism during submandibular gland development using embryonic and postnatal mice. In addition, a glycogenolysis inhibition experiment was conducted in organ culture systems of submandibular gland tissues. From embryonic day 13.5 (E13.5), glycogen synthesis started in the salivary epithelial cells, and glycogen accumulation and degradation occurred at E15.5. Conversely, in the submandibular gland tissue around birth, the number of glycogen-retained cells increased, and active glycogen synthesis and degradation occurred in acinar cells and terminal tubules. In an in vitro organ culture experiment, early branching morphogenesis was disturbed by a glycogen phosphorylase inhibitor, which significantly inhibited differentiation into acinar and myoepithelial cells. These results suggest the important role of the glycogen shunt in early growth and cell differentiation during submandibular gland development.