Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the incretins released from enteroendocrine K-cells and L-cells, respectively, in response to nutrient ingestion to potentiate glucose-stimulated insulin secretion. We previously reported that GIP is involved in compensatory insulin hypersecretion in high fat diet (HFD)-induced obesity. To clarify the mechanism, we established GIP-GFP knock-in (GIP-GFP) mice to visualize K-cells by EGFP and identified regulatory factor X 6 (Rfx6), expressed exclusively in K-cells, by microarray analysis of isolated K-cells of these mice. Our in vitro and in vivo study suggests that Rfx6 increases GIP expression and content in K-cells and is involved in GIP hypersecretion in HFD-induced obesity. Fat-induced GIP is thought to stimulate insulin secretion through the GIP receptor (GIPR) expressed on pancreatic β-cells. However, GIPR is also expressed on adipose tissue, and the contribution of the direct effects of GIP on adipose tissue in HFD-induced obesity is not well known. Recently, we established adipose-tissue specific GIPR-deficient mice, which reveal that inhibition of GIPR signaling in adipose tissue improves insulin resistance. It is known that pancreatic β-cell mass is decreased in type 2 diabetes (T2DM) and may be involved in the progression of T2DM. We reported that GLP-1 restores glucose metabolism and glucose-induced insulin secretion in the β-cells of Goto-Kakizaki (GK) rats, a non-obese diabetic model with insulin failure. We also reported that GLP-1 protects pancreatic islet transplant by inhibiting apoptosis. These results suggest that GLP-1 may halt the progression of T2DM through preservation of β-cell mass. Non-invasive imaging of pancreatic β-cells is an unmet need required, and I will introduce the recent progress of our study.