Article Text

PDF

S3
GLUCAGON-LIKE PEPTIDE-1 PROTECTS AGAINST CARDIAC DYSFUNCTION AND EXTRACELLULAR MATRIX REMODELLING IN EXPERIMENTAL DIABETES
  1. M Tate*,
  2. E Robinson,
  3. B J McDermott,
  4. D J Grieve
  1. Queen's University Belfast, Centre for Vision and Vascular Science, School of Medicine, Dentistry and Biomedical Sciences, Grosvenor Road, Belfast BT12 6BA

    Abstract

    Glucagon-like peptide-1 (GLP-1) is an insulin-releasing hormone with established cardiovascular actions. Here, we investigated effects of exendin-4, a stable GLP-1 mimetic, on cardiac remodelling in experimental diabetes. Male C57BL/6J mice were injected with streptozotocin (STZ; 50 mg/kg/day for 5 days) or vehicle control prior to starting infusion with exendin-4 (25 nmol/kg/day) at 4 weeks. Continuous treatment with exendin-4 for 8 weeks had no effect on body weight but reduced blood glucose in STZ-treated animals (HbA1c: control 6.6±0.3 vs STZ saline 11.8±1.1, p<0.01; exendin-4 9.4±0.9 vs STZ exendin-4 6.5±0.3%, p=NS; n=4–9). Echocardiography indicated that systolic function, assessed by fractional shortening, was similar between groups. However, diastolic dysfunction observed after STZ treatment was attenuated by exendin-4 (mitral valve E/A: STZ saline 1.17±0.04 vs STZ exendin-4 1.51±0.09, p<0.05; n=3–8). Interestingly, these functional effects were associated with an improved pro-fibrotic gene expression profile, as assessed by real-time RT-PCR. For example, expression of procollagen I mRNA was reduced in STZ animals after exendin-4 treatment (STZ saline 4.32±0.27 vs STZ exendin-4 3.02±0.37 arbitrary units, p<0.05; n=5–8), and similar patterns were observed for procollagen III and fibronectin. Furthermore, differential STZ-induced effects on mRNA expression of matrix metalloproteinase-2 (MMP-2) (control 7.30±0.46 vs STZ saline 9.21±0.49, p<0.05; exendin-4 6.50±0.11 vs STZ exendin-4 7.70±0.45 arbitrary units, p=NS; n=5–7) and MMP-9 (STZ saline 1.70±0.35 vs STZ exendin-4 3.84±0.63 arbitrary units, p<0.05; n=5–8) were inhibited by exendin-4. These data indicate that GLP-1 protects against adverse cardiac remodelling in diabetes via modulation of the extracellular matrix, although the underlying mechanisms remain unclear.

    Statistics from Altmetric.com

    Request permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.