HFD-fed WT and GLP-1R−/− mice were treated with or without DPP-IV inhibitor by drinking water. Food and water intake and body weight were measured during 8 weeks of study. CT-based body composition analysis, Oral glucose tolerance test (OGTT), batch incubation study for insulin secretion and quantitative RT-PCR for expression of incretin receptors in isolated islets were performed at the end of study.
DPP-IV inhibitor had no effect on food and water intake and body weight, but increased body fat mass in GLP-1R−/− mice. DPP-IV inhibitor-treated WT and GLP-1R−/− mice both showed increased insulin secretion in OGTT. In isolated islets of DPP-IV inhibitor-treated WT and GLP-1R−/− mice, glucose-induced insulin secretion was increased and insulin secretion in response to GLP-1 or GIP was preserved, without downregulation of incretin receptor expression.
Long-term DPP-IV inhibition may maintain body composition through counteracting effects of GLP-1 and GIP while improving glucose tolerance by increasing glucose-induced insulin secretion through the synergistic effects of GLP-1 and GIP.