L Li1, G Yang, Q Li, X Tan, H Liu, Y Tang, G Boden. 1. Department of Clinical Biochemistry in Chongqing Medical University and The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education, Chongqing, China. lingli31@yahoo.com.cn
Abstract
BACKGROUND: Exenatide (exendin-4) can reduce blood glucose levels, increase insulin secretion and improve insulin sensitivity through mechanisms that are not completely understood. METHODS: In the present study, we examined the effects of exenatide treatment on glucose tolerance (intravenous glucose tolerance test), insulin sensitivity (euglycaemic-hyperinsulinaemic clamps), insulin signalling (insulin receptor substrate 1 tyrosine phosphorylation) and adipocytokine levels (visfatin and adiponectin) in high fat-fed rats. RESULTS: Administration of exenatide (0.5 or 2.0 mug/kg twice daily x 6 weeks) prevented high-fat diet (HFD)-induced increases in body weight, plasma free fatty acids, triglycerides and total cholesterol. Exenatide also prevented HFD-induced deterioration in peripheral and hepatic insulin sensitivity, insulin clearance, glucose tolerance and decreased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in fat and skeletal muscles. Interestingly, plasma visfatin levels decreased in exenatide-treated rats, whereas expression and plasma levels of adiponectin increased. CONCLUSIONS: These results indicate that chronic exenatide treatment enhances insulin sensitivity and protects against high fat-induced insulin resistance.
BACKGROUND:Exenatide (exendin-4) can reduce blood glucose levels, increase insulin secretion and improve insulin sensitivity through mechanisms that are not completely understood. METHODS: In the present study, we examined the effects of exenatide treatment on glucose tolerance (intravenous glucose tolerance test), insulin sensitivity (euglycaemic-hyperinsulinaemic clamps), insulin signalling (insulin receptor substrate 1 tyrosine phosphorylation) and adipocytokine levels (visfatin and adiponectin) in high fat-fed rats. RESULTS: Administration of exenatide (0.5 or 2.0 mug/kg twice daily x 6 weeks) prevented high-fat diet (HFD)-induced increases in body weight, plasma free fatty acids, triglycerides and total cholesterol. Exenatide also prevented HFD-induced deterioration in peripheral and hepatic insulin sensitivity, insulin clearance, glucose tolerance and decreased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in fat and skeletal muscles. Interestingly, plasma visfatin levels decreased in exenatide-treated rats, whereas expression and plasma levels of adiponectin increased. CONCLUSIONS: These results indicate that chronic exenatide treatment enhances insulin sensitivity and protects against high fat-induced insulin resistance.
Authors: Konrad Talbot; Hoau-Yan Wang; Hala Kazi; Li-Ying Han; Kalindi P Bakshi; Andres Stucky; Robert L Fuino; Krista R Kawaguchi; Andrew J Samoyedny; Robert S Wilson; Zoe Arvanitakis; Julie A Schneider; Bryan A Wolf; David A Bennett; John Q Trojanowski; Steven E Arnold Journal: J Clin Invest Date: 2012-04 Impact factor: 14.808
Authors: Fiona C McGillicuddy; Elise H Chiquoine; Christine C Hinkle; Roy J Kim; Rachana Shah; Helen M Roche; Emer M Smyth; Muredach P Reilly Journal: J Biol Chem Date: 2009-09-23 Impact factor: 5.157