Research

We are doing research in the field of endocrinology and metabolism with a special interest in the molecular mechanisms of energy metabolism by hormones and nutrients.

Ghrelin research

Ghrelin is a stomach-derived hormone with potent appetite- and growth hormone-stimulating activities. We are doing research to dissect the molecular mechanisms involved in the regulation of ghrelin production and secretion by using originally-developed ghrelin-secreting cell lines. One of our goals is to develop ghrelin-regulating drugs to treat diseases such as cachexia, somatopause, or sarcopenia.

Previous our works:

Regulation of ghrelin secretion
The regulation of ghrelin secretion

Previously, we developed a ghrelin-secreting cell line, MGN3-1 cells, from a ghrelinoma originated from a ghrelin-promoter SV40-Tag transgenic mouse. MGN3-1 cells produce a substantial amount of ghrelin with physiological processing and acyl-modification. We found that ghrelin secretion is regulated by autonomic nerves, peptide hormones (oxytocin and somatostatin), nutrients (lactate, tryptophan, and lipids), and cytokines (PGE2 and IL-1β) (Koyama, Iwakura et al. Endocrinology 2016, Bando, Iwakura et al. Mol Cell Endo 2017).

Origin of octanoic acids for acyl-modification of ghrelin

We found that ghrelin-producing cells have a higher ability to incorporate long-chain fatty acids, with a relatively slow progression of β-oxidation of medium-chain fatty acids. We think that octanoic acids are effectively provided for the acyl-modification by these characteristics of the ghrelin-producing cells (Bando et al. FEBS Lett. 2016).

GPR142 Research

GPR142 is a G-protein coupled receptor, whose most potent ligand is tryptophan. GPR142 expression is observed in enteroendocrine cells and pancreatic islet cells, where the receptor senses tryptophan to regulate the secretion of hormones. We have found that GPR142 and CaSR have a different role in the stimulation of insulin secretion by tryptophan in obese and lean animals (Ueda et al. PLos One 2018).