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Novel Role of Glucagon as a Physiological Defender Against Catecholamine Surge Via Its Direct Action on Adrenomedullary Differentiation

82 Pages Posted: 9 Apr 2020 Sneak Peek Status: Review Complete

See all articles by Kazuyuki Nishimura

Kazuyuki Nishimura

Nagoya University - Department of Cardiology

Yasuko K. Bando

Nagoya University - Department of Cardiology

Yusuke Seino

Nagoya University

Atsushi Iida

Nagoya Central Hospital

Takahiro Kamihara

Nagoya University - Department of Cardiology

Akitoshi Hara

Nagoya University

Mikito Takefuji

Nagoya University - Department of Cardiology

Atsushi Enomoto

Nagoya University - Department of Pathology

Atsushi Suzuki

Fujita Health University

Yasheng Remina

Nagoya University - Department of Cardiology

Reina Ozaki

Nagoya University - Department of Cardiology

Yoshitaka Hayashi

Nagoya University

Toyoaki Murohara

Nagoya University - Department of Cardiology

More...

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.

Keywords: glucagon, catecholamine, heart failure, hypoglycemia

Suggested Citation

Nishimura, Kazuyuki and Bando, Yasuko K. and Seino, Yusuke and Iida, Atsushi and Kamihara, Takahiro and Hara, Akitoshi and Takefuji, Mikito and Enomoto, Atsushi and Suzuki, Atsushi and Remina, Yasheng and Ozaki, Reina and Hayashi, Yoshitaka and Murohara, Toyoaki, Novel Role of Glucagon as a Physiological Defender Against Catecholamine Surge Via Its Direct Action on Adrenomedullary Differentiation. Available at SSRN: https://ssrn.com/abstract=3565019 or http://dx.doi.org/10.2139/ssrn.3565019
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Kazuyuki Nishimura

Nagoya University - Department of Cardiology

Japan

Yasuko K. Bando (Contact Author)

Nagoya University - Department of Cardiology ( email )

Japan

Yusuke Seino

Nagoya University

Furo-cho, Chikusa-ku
Nagoya-City, 4648601
Japan

Atsushi Iida

Nagoya Central Hospital

Japan

Takahiro Kamihara

Nagoya University - Department of Cardiology

Japan

Akitoshi Hara

Nagoya University

Furo-cho, Chikusa-ku
Nagoya-City, 4648601
Japan

Mikito Takefuji

Nagoya University - Department of Cardiology

Japan

Atsushi Enomoto

Nagoya University - Department of Pathology

Furo-cho, Chikusa-ku
Nagoya-City, 4648601
Japan

Atsushi Suzuki

Fujita Health University ( email )

Toyoake, Aichi
Japan

Yasheng Remina

Nagoya University - Department of Cardiology

Japan

Reina Ozaki

Nagoya University - Department of Cardiology

Japan

Yoshitaka Hayashi

Nagoya University

Furo-cho, Chikusa-ku
Nagoya-City, 4648601
Japan

Toyoaki Murohara

Nagoya University - Department of Cardiology

Japan

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