Advertisement

Lack of Glucagon Promotes Cardiac Remodeling and Hypertension in Mice via Elevation of Norepinephrine

      Background: Glucagon (Gcg) maintains blood glucose level to the physiological extent in response to various pathophysiological conditions. Previous studies suggest that Gcg promotes chronotropic and inotropic effects on heart; however, current understanding regarding the cardiovascular impact of Gcg remains quite limited. In the present study, by use of Gcg-null mice, we aimed to seek for the pathophysiological role(s) of Gcg on cardiac function and remodeling. Methods and Results: Gcg-null mice [18 week-old male Gcg-enhanced green fluorescent protein (EGFP) knock-in mice] exhibited marked left ventricular dilatation [in mm; LVDd/Ds 3.9/2.9 (Gcg-null) and 3.6/2.1 (wild)] and consequent reduction in left-ventricular systolic function [(LVFS; 27.2% (Gcg-null) and 42.5% (wild)). Their left ventricular wall thick remained normal range and electron microscopy revealed the decline in mitochondrial count in Gcg-null heart. Gcg-null mice exhibited hypertension and cardiac catheterization consistently revealed elevation of arterial blood pressure and diastolic dysfunction [dp/dtmin, Tau, and left ventricular maximum pressure (Pmax)]. Picrosirius red staining revealed that enhanced perivascular fibrosis in Gcg null heart. Interestingly, the circulating angiotensin-II concentration was decreased; however, the norepinephrine level of Gcg-null mice was more than 3 fold higher than wild type counterpart. Conclusions: The present study revealed the possible link between Gcg and sympathetic nerve activity which modulates cardiac remodeling and blood pressure, implicating a novel pathophysiological pathway that contributes to development of heart failure.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Cardiac Failure
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect