Regulation of gastric hormones by systemic rapamycin

The mammalian target of rapamycin (mTOR), an evolutionarily conserved serine-threonine kinase, is an intracellular fuel sensor critical for cellular energy homeostasis. Gastrointestinal endocrine cells play a vital role in the regulation of energy balance by secreting hormones that inform the brain about energy supply. Here we showed the localization of mTOR signaling molecules in more than 90% of gastric ghrelin cells and 36 ± 3% of gastrin cells, while no somatostatin-positive cell showed phospho-S6K1 immunoreactivity. Inhibition of mTOR significantly stimulated expression of gastric ghrelin mRNA and protein, and the concentration of plasma ghrelin (2.06 ± 0.34 ng/ml vs. 12.53 ± 3.9 ng/ml, p < 0.05), inhibited gastrin synthesis and secretion (75.01 ± 6.71 pg/ml vs. 54.04 ± 3.65 pg/ml, p < 0.05), but had no effect on somatostatin production (165.2 ± 25.07 pg/ml vs. 178.9 ± 29.14 pg/ml, p = 0.73). Gastric mTOR is a gastric sensor whose activity is linked to the differential regulation of gastric hormone production and release.

Research highlights▶ mTOR signaling molecules are expressed in gastric endocrine cells. ▶ Ghrelin-positive cells express pmTOR, rapamycin stimulates ghrelin production. ▶ 1/3 gastrin-positive cells express pS6K1, rapamycin inhibits gastrin synthesis. ▶ Somatostatin-immunoreactive cells do not express pS6K1.