Effects of long-term dipeptidyl peptidase-IV inhibition on body composition and glucose tolerance in high fat diet-fed mice.

Abstract

AIM:

Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are major incretins associated with body weight regulation. Dipeptidyl peptidase-IV (DPP-IV) inhibitor increases plasma active GLP-1 and GIP. However, the magnitude of the effects of enhanced GLP-1 and GIP signaling by long-term DPP-IV inhibition on body weight and insulin secretion has not been determined. In this study, we compared the effects of long-term DPP-IV inhibition on body composition and insulin secretion of high fat diet (HFD)-fed wild-type (WT) and GLP-1R knockout (GLP-1R(-/-)) mice.

MAIN METHODS:

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.

KEY FINDINGS:

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.

SIGNIFICANCE:

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.

• Authors: Xibao Liu, Norio Harada, Shunsuke Yamane, Lisa Kitajima, Saeko Uchida, Akihiro Hamasaki, Eri Mukai, Kentaro Toyoda, Chizumi Yamada, Yuichiro Yamada, Yutaka Seino, Nobuya Inagaki
• Journal: Life sciences (Life Sci) Vol. 84 Issue 25-26 Pg. 876-81 (Jun 19 2009) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 19358859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Dietary Fats
• Dipeptidyl-Peptidase IV Inhibitors
• Insulin
• RNA, Messenger
• Gastric Inhibitory Polypeptide
• Glucagon-Like Peptide 1
• Dipeptidyl Peptidase 4

Topics

• Animals
• Blood Glucose (analysis, metabolism)
• Body Composition
• Body Weight
• Dietary Fats (administration & dosage)
• Dipeptidyl Peptidase 4 (metabolism)
• Dipeptidyl-Peptidase IV Inhibitors (administration & dosage, metabolism)
• Gastric Inhibitory Polypeptide (genetics, metabolism)
• Gene Expression
• Glucagon-Like Peptide 1 (genetics, metabolism)
• Glucose Tolerance Test
• Insulin (metabolism)
• Insulin Secretion
• Islets of Langerhans (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• RNA, Messenger (genetics)
• Time Factors