Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2011 Apr 1;407(1):153-7. doi: 10.1016/j.bbrc.2011.02.129. Epub 2011 Mar 1.

Chronic administration of ezetimibe increases active glucagon-like peptide-1 and improves glycemic control and pancreatic beta cell mass in a rat model of type 2 diabetes.

Author information

1
Diabetes Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Abstract

Ezetimibe is a cholesterol-lowering agent targeting Niemann-Pick C1-like 1, an intestinal cholesterol transporter. Inhibition of intestinal cholesterol absorption with ezetimibe may ameliorate several metabolic disorders including hepatic steatosis and insulin resistance. In this study, we investigated whether chronic ezetimibe treatment improves glycemic control and pancreatic beta cell mass, and alters levels of glucagon-like peptide-1 (GLP-1), an incretin hormone involved in glucose homeostasis. Male LETO and OLETF rats were treated with vehicle or ezetimibe (10 mg kg(-1)day(-1)) for 20 weeks via stomach gavage. OLETF rats were diabetic with hyperglycemia and significant decreases in pancreatic size and beta cell mass compared with LETO lean controls. Chronic treatment of OLETF rats with ezetimibe improved glycemic control during oral glucose tolerance test compared with OLETF controls. Moreover, ezetimibe treatment rescued the reduced pancreatic size and beta cell mass in OLETF rats. Interestingly, ezetimibe significantly decreased serum dipeptidyl peptidase-4 activity and increased serum active GLP-1 in OLETF rats without altering serum total GLP-1. These findings demonstrated that chronic administration of ezetimibe improves glycemic control and pancreatic beta cell mass, and increases serum active GLP-1 levels, suggesting possible involvement of GLP-1 in the ezetimibe-mediated beneficial effects on glycemic control.

PMID:
21371430
DOI:
10.1016/j.bbrc.2011.02.129
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center