Murine remote ischemic preconditioning upregulates preferentially hepatic glucose transporter-4 via its plasma membrane translocation, leading to accumulating glycogen in the liver

• Published in: Life sciences (1973) 2022-02, Vol.290, p.120261-120261, Article 120261
• Main Authors: Kurabayashi, Atsushi, Furihata, Kaoru, Iwashita, Waka, Tanaka, Chiharu, Fukuhara, Hideo, Inoue, Keiji, Furihata, Mutsuo, Kakinuma, Yoshihiko
• Format: Article
• Language: English
• Subjects: Acetylcholine; Animals; Boundaries; Cell Membrane - metabolism; Gene expression; Gene Expression - genetics; Gene Expression Regulation - genetics; Glucose; Glucose - metabolism; Glucose transporter; Glucose Transporter Type 2 - genetics; Glucose Transporter Type 2 - metabolism; Glucose Transporter Type 4 - genetics; Glucose Transporter Type 4 - metabolism; Glycogen; Glycogen - metabolism; Glycogens; Hepatocytes; Hepatocytes - metabolism; Immunofluorescence; Immunoreactivity; In vivo methods and tests; Incubation; Insulin - metabolism; Ischemia; Ischemia-reperfusion; Ischemic Preconditioning - methods; Liver; Liver - metabolism; Male; Membranes; Mice; Mice, Inbred C57BL; Molecular weight; mRNA; Nervous system; Parasympathetic nervous system; Preconditioning; Reperfusion; Reperfusion Injury - metabolism; Translocation; Western blotting
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.120261

We previously showed that hindlimb ischemia-reperfusion (IR) enhanced glucose uptake in the liver through the activation of the parasympathetic nervous system. Although we suggested that the key glucose transporter (GLUT) in this hepatic glucose uptake was GLUT4 by western blotting, the molecular weight of GLUT4 was nearly the same as that of GLUT2, which is predominantly expressed in the liver. We primarily conducted a histological evaluation to determine whether IR specifically accelerates the overexpression of GLUT4, rather than GLUT2, in the hepatocytes in vitro and in vivo. A total of 54 male C57BL/6J mice were used and subjected to 3 min hindlimb ischemia repeated three times with 3 min interval. Focusing on the area connecting portal and central veins, the GLUT4 and GLUT2 expression in the hepatocytes were examined by real-time PCR and immunohistochemically. Moreover, the alteration of GLUT4 and GLUT2 expression by acetylcholine in the primary hepatocytes were examined by immunofluorescence. IR significantly upregulated the GLUT4, rather than GLUT2, expression in both mRNA and protein in the liver. Histological examination revealed marked glycogen storage in zone1, the periportal area, coincident with the enhanced GLUT4 immunoreactivity, in the IR-treated liver. Incubation of primary hepatocytes with acetylcholine induced the appearance of GLUT4 on the membrane peripheries. The overexpression of GLUT4 on the membrane peripheries contributed to increasing glucose uptake found in IR-treated livers. This acceleration of glucose uptake via GLUT4 may induce marked glycogen storage in zone1 through energy production linked with increased glucose preference. •IR upregulated the GLUT4 expression in both mRNA and protein in the liver.•Marked glycogen storage in the periportal area in the IR-treated liver.•ACh induced the GLUT4 expression on the membrane peripheries in primary hepatocytes.