Transcriptional factor pancreatic duodenal homeobox-1 (Pdx1) is involved in age-related GIP hypersecretion in mice

Fat accumulation with aging is a serious problem; glucose-dependent insulinotropic polypeptide (GIP) is an incretin that plays an important role in fat accumulation. GIP receptor-knockout mice show reduced fat mass and improved insulin sensitivity associated with aging. Therefore, GIP is involved in fat accumulation and insulin resistance with aging. However, age-related changes of GIP secretion remain unclear. The present study aimed to elucidate age-related changes of GIP secretion and enteroendocrine K cells using GIP reporter (GIP-GFP knock-in heterozygous; GIPgfp/+) mice. Aged (1 year old GIPgfp/+) mice exhibited a phenotype of fat accumulation, insulin resistance, and GIP hypersecretion compared with young (3-4 months old GIPgfp/+) mice. In aged mice, K cell number in small intestine and the mRNA expression levels of GIP and transcriptional factor pancreatic and duodenal homeobox-1 (Pdx1) in K cells were increased. K cell number, GIP mRNA expression and content in small intestine, and GIP secretion ...