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 |
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Authors: | Yang Soo Jin Choi Jung Mook Kim Lisa Kim Byung-Joon Sohn Jin Hee Kim Won Jun Park Se Eun Rhee Eun Jung Lee Won Young Oh Ki Won Park Sung Woo Kim Sun Woo Park Cheol-Young |
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Institution: | aDiabetes Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;bDivision of Endocrinology, Department of Internal Medicine, Konyang University, School of Medicine, Daejeon, Republic of Korea;cDepartment of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;dDivision of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Republic of Korea |
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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. |
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Keywords: | Abbreviations: ABCG5 ATP binding cassette transporters G5 DPP-4 dipeptidyl peptidase-4 FFA free fatty acids GLP-1 glucagon-like peptide-1 NASH non-alcoholic steatohepatitis NPC1L1 Niemann-Pick C1-like 1 TC total cholesterol TG triglyceride |
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