Abstract 1102: Chronic Glucagon-Like Peptide-1 (GLP-1) Increases Survival in Obese, Hypertensive Rats in Association with Increased Cardiac Mass, Increased Glucose Uptake and Reduced Myocyte Apoptosis
Background: GLP-1 is an insulinotropic and insulinomimetic peptide that has been associated with short term improvements in myocardial function in both ischemic and non-ischemic cardiomyopathy. It is unknown whether GLP-1, and by what mechanism, improves survival when administered over a longer period. Spontaneously hypertensive, heart failure prone rats (SHHF) progress to advanced heart failure and death over a 15 month period. We sought to determine whether a continuous infusion of GLP-1 would prolong survival in this model of obesity, insulin resistance, and hypertension.
Methods: Forty SHHF rats were randomized at 9 months of age to receive continuous intra-peritoneal infusion of GLP-1 (1.5 pmol/kg/min) or saline via Alzet® mini-osmotic pumps for three months. SHHF had measurements of metabolic parameters and cardiac echoes before and at three months following treatment. The surviving rats were euthanized at 12 months and hearts, perfused in an isolated isovolumic heart preparation. Myocardial samples were prepared for TUNEL staining to determine whether GLP-1 affected apoptosis.
Results: There was no difference in baseline metabolic or cardiac functional parameters. GLP-1 treated SHHF had greater (* p<0.05) survival (Con: 46%; GLP-1: 80%*) at 12 months of age. GLP-1 treated SHHF had higher plasma insulin (Con: 2.9±0.3; GLP-1: 4.2±0.25 nmol/L*), lower plasma triglycerides (Con: 1.8±0.3; GLP-1: 0.9±0.2 mmol/L*), preserved LV Function (Con: 64±5%; GLP-1: 75±4%*), and increased LV mass index (Con: 11.0±1.18; GLP-1: 17.6±0.6 g/m2*). TUNEL staining revealed increased myocyte apoptosis in controls (Con: 0.18±0.04%; GLP-1: 0.27± 0.06%*). The LVP (Con: 109±4; GLP-1: 115±4 mmHg) and LVDevP (Con: 107±4; GLP-1: 113±4 mmHg) were preserved in the GLP-1 treated SHHF, but myocardial glucose uptake (Con: 2.0±0.2; GLP-1: 3.3±0.5 μmol/min*) was increased in GLP-1 treated SHHF.
Conclusion: Chronic GLP-1 treatment prolongs survival in obese, hypertensive SHHF rats. This is associated with preserved LV function, increased LV mass, increased myocardial glucose uptake and reduced myocyte apoptosis.