A mouse model of ghrelinoma exhibited activated growth hormone-insulin-like growth factor I axis and glucose intolerance

Ghrelin is a stomach-derived peptide that has growth hormone-stimulating and orexigenic activities. Although there have been several reports of ghrelinoma cases, only a few cases have elevated circulating ghrelin levels, hampering the investigation of pathophysiological features of ghrelinoma and chronic effects of ghrelin excess. Furthermore, standard transgenic technique has resulted in desacyl ghrelin production only because of the limited tissue expression of ghrelin O-acyltransferase, which mediates acylation of ghrelin. Accordingly, we attempted to create ghrelin promoter SV40 T-antigen transgenic (GP-Tag Tg) mice, in which ghrelin-producing cells continued to proliferate and finally developed into ghrelinoma. Adult GP-Tag Tg mice showed elevated plasma ghrelin levels with preserved physiological regulation. Adult GP-Tag Tg mice with increased plasma ghrelin levels exhibited elevated IGF-I levels despite poor nutrition. Although basal growth hormone levels were not changed, those after growth hormon...