BACKGROUND: Glucagon-like peptide-1 (GLP-1) treatment leads to short-term improvements in myocardial function in ischemic and nonischemic cardiomyopathy. It is unknown whether GLP-1 improves survival when administered over a longer time period. Spontaneously hypertensive, heart failure-prone (SHHF) rats progress to advanced heart failure and death over a 15-month period. The authors sought to determine whether a continuous infusion of GLP-1 would reduce mortality in this model. METHODS AND RESULTS: At 9 months of age, 50 SHHF rats were randomized to receive a 3-month, continuous infusion of either GLP-1 or saline. Metabolic parameters were measured and cardiac ultrasounds performed at study initiation and completion of treatment. Surviving rats were euthanized at 12 months. Hearts were perfused in an isolated, isovolumic heart preparation, and Tunel staining of myocardial samples was performed. Baseline metabolic and cardiac functional parameters were comparable. GLP-1-treated SHHF rats had greater survival (72% versus 44%, P=0.008) at 12 months of age. In addition, GLP-1 treatment led to higher plasma insulin, lower plasma triglycerides, and preserved left ventricular (LV) function. GLP-1-treated rats demonstrated decreased myocyte apoptosis by Tunel staining as well as reduced caspase-3 activation. No increase in p-BAD expression was seen. In isolated hearts, the LV systolic pressure and LV-developed pressure were greater in the GLP-1 group. Myocardial glucose uptake was also increased in GLP-1-treated SHHF rats. CONCLUSIONS: Chronic GLP-1 treatment prolongs survival in obese SHHF rats. This is associated with preserved LV function and LV mass index, increased myocardial glucose uptake, and reduced myocyte apoptosis.
BACKGROUND:Glucagon-like peptide-1 (GLP-1) treatment leads to short-term improvements in myocardial function in ischemic and nonischemic cardiomyopathy. It is unknown whether GLP-1 improves survival when administered over a longer time period. Spontaneously hypertensive, heart failure-prone (SHHF) rats progress to advanced heart failure and death over a 15-month period. The authors sought to determine whether a continuous infusion of GLP-1 would reduce mortality in this model. METHODS AND RESULTS: At 9 months of age, 50 SHHFrats were randomized to receive a 3-month, continuous infusion of either GLP-1 or saline. Metabolic parameters were measured and cardiac ultrasounds performed at study initiation and completion of treatment. Surviving rats were euthanized at 12 months. Hearts were perfused in an isolated, isovolumic heart preparation, and Tunel staining of myocardial samples was performed. Baseline metabolic and cardiac functional parameters were comparable. GLP-1-treated SHHFrats had greater survival (72% versus 44%, P=0.008) at 12 months of age. In addition, GLP-1 treatment led to higher plasma insulin, lower plasma triglycerides, and preserved left ventricular (LV) function. GLP-1-treated rats demonstrated decreased myocyte apoptosis by Tunel staining as well as reduced caspase-3 activation. No increase in p-BAD expression was seen. In isolated hearts, the LV systolic pressure and LV-developed pressure were greater in the GLP-1 group. Myocardial glucose uptake was also increased in GLP-1-treated SHHFrats. CONCLUSIONS: Chronic GLP-1 treatment prolongs survival in obese SHHFrats. This is associated with preserved LV function and LV mass index, increased myocardial glucose uptake, and reduced myocyte apoptosis.
Authors: S C Bodine; T N Stitt; M Gonzalez; W O Kline; G L Stover; R Bauerlein; E Zlotchenko; A Scrimgeour; J C Lawrence; D J Glass; G D Yancopoulos Journal: Nat Cell Biol Date: 2001-11 Impact factor: 28.824
Authors: M A Quinones; A D Waggoner; L A Reduto; J G Nelson; J B Young; W L Winters; L G Ribeiro; R R Miller Journal: Circulation Date: 1981-10 Impact factor: 29.690
Authors: TracyAnn Perry; Norman J Haughey; Mark P Mattson; Josephine M Egan; Nigel H Greig Journal: J Pharmacol Exp Ther Date: 2002-09 Impact factor: 4.030
Authors: Santanu Guha; S Harikrishnan; Saumitra Ray; Rishi Sethi; S Ramakrishnan; Suvro Banerjee; V K Bahl; K C Goswami; Amal Kumar Banerjee; S Shanmugasundaram; P G Kerkar; Sandeep Seth; Rakesh Yadav; Aditya Kapoor; Ajaykumar U Mahajan; P P Mohanan; Sundeep Mishra; P K Deb; C Narasimhan; A K Pancholia; Ajay Sinha; Akshyaya Pradhan; R Alagesan; Ambuj Roy; Amit Vora; Anita Saxena; Arup Dasbiswas; B C Srinivas; B P Chattopadhyay; B P Singh; J Balachandar; K R Balakrishnan; Brian Pinto; C N Manjunath; Charan P Lanjewar; Dharmendra Jain; Dipak Sarma; G Justin Paul; Geevar A Zachariah; H K Chopra; I B Vijayalakshmi; J A Tharakan; J J Dalal; J P S Sawhney; Jayanta Saha; Johann Christopher; K K Talwar; K Sarat Chandra; K Venugopal; Kajal Ganguly; M S Hiremath; Milind Hot; Mrinal Kanti Das; Neil Bardolui; Niteen V Deshpande; O P Yadava; Prashant Bhardwaj; Pravesh Vishwakarma; Rajeeve Kumar Rajput; Rakesh Gupta; S Somasundaram; S N Routray; S S Iyengar; G Sanjay; Satyendra Tewari; Sengottuvelu G; Soumitra Kumar; Soura Mookerjee; Tiny Nair; Trinath Mishra; U C Samal; U Kaul; V K Chopra; V S Narain; Vimal Raj; Yash Lokhandwala Journal: Indian Heart J Date: 2018-06-08