Abstract
The regulatory role of physiological glucagon (Gcg) in the cardiovascular system remains uncertain. Employing a mouse model harboring a functional deficiency of the preproglucagon gene (GCG-null), we found that lack of endogenous Gcg caused hypertension and systolic left ventricular (LV) dysfunction due to abnormal rise in circulating epinephrine (Ep) level, which was completely restored by the supplemental injection of Gcg (Sup-Gcg) or adrenergic β1-receptor blockers. More interestingly, GCG-null exhibited adrenal hypertrophy with the upregulation of phenylethanolamine N-methyltransferase (PNMT), a key enzyme that synthesizes Ep. Gcg directly facilitated mRNA decay via augmentation of enhancer of mRNA decapping protein 4 (EDC4) in a PKA-dependent fashion, thereby suppressing PNMT in adrenal chromaffin cells. Our data unveiled the novel action of Gcg like a circuit breaker against the Ep surge in the context of disease condition.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
