title: Liver autophagy contributes to the maintenance of blood glucose and amino acid levels.
abstract: Both anabolism and catabolism of the amino acids released by starvation-induced autophagy are essential for cell survival, but their actual metabolic contributions in adult animals are poorly understood. Herein, we report that, in mice, liver autophagy makes a significant contribution to the maintenance of blood glucose by converting amino acids to glucose via gluconeogenesis. Under a synchronous fasting-initiation regimen, autophagy was induced concomitantly with a fall in plasma insulin in the presence of stable glucagon levels, resulting in a robust amino acid release. In liver-specific autophagy (Atg7)-deficient mice, no amino acid release occurred and blood glucose levels continued to decrease in contrast to those of wild-type mice. Administration of serine (30 mg/animal) exerted a comparable effect, raising the blood glucose levels in both control wild-type and mutant mice under starvation. Thus, the absence of the amino acids that were released by autophagic proteolysis is a major reason for a decrease in blood glucose. Autophagic amino acid release in control wild-type livers was significantly suppressed by the prior administration of glucose, which elicited a prompt increase in plasma insulin levels. This indicates that insulin plays a dominant role over glucagon in controlling liver autophagy. These results are the first to show that liver-specific autophagy plays a role in blood glucose regulation.
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Ezaki
authors.forename: Naomi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Mitsue
authors.initials: M
authors.lastname: Takeda-Ezaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hiraoka
authors.forename: Hikari
authors.initials: H
authors.lastname: Taka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujimura
authors.forename: Kenji
authors.initials: K
authors.lastname: Takehana
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Yoshida
authors.forename: Junichi
authors.initials: J
authors.lastname: Iwata
authors.forename: Isei
authors.initials: I
authors.lastname: Tanida
authors.forename: Norihiko
authors.initials: N
authors.lastname: Furuya
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zheng
authors.forename: Norihiro
authors.initials: N
authors.lastname: Tada
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Eiki
authors.initials: E
authors.lastname: Kominami
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueno
mesh_terms: D000596:Amino Acids / Q000097:blood*; D000818:Animals; D001343:Autophagy; D001786:Blood Glucose / Q000378:metabolism*; D005215:Fasting / Q000097:blood; D005227:Fatty Acids / Q000097:blood; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis; D007328:Insulin / Q000097:blood; D008099:Liver / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D013217:Starvation; D014280:Triglycerides / Q000097:blood; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D014280:Triglycerides; D005934:Glucagon