Direct and indirect control of hepatic glucose production by insulin.

Lewis, GF ; Carpentier, AC ; et al.

In: Cell metabolism, Jg. 33 (2021-04-06), Heft 4, S. 709-720

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There is general agreement that the acute suppression of hepatic glucose production by insulin is mediated by both a direct and an indirect effect on the liver. There is, however, no consensus regarding the relative magnitude of these effects under physiological conditions. Extensive research over the past three decades in humans and animal models has provided discordant results between these two modes of insulin action. Here, we review the field to make the case that physiologically direct hepatic insulin action dominates acute suppression of glucose production, but that there is also a delayed, second order regulation of this process via extrahepatic effects. We further provide our views regarding the timing, dominance, and physiological relevance of these effects and discuss novel concepts regarding insulin regulation of adipose tissue fatty acid metabolism and central nervous system (CNS) signaling to the liver, as regulators of insulin's extrahepatic effects on glucose production.

Competing Interests: Declaration of interests The authors declare no competing interests.

Titel:	Direct and indirect control of hepatic glucose production by insulin.
Autor/in / Beteiligte Person:	Lewis, GF ; Carpentier, AC ; Pereira, S ; Hahn, M ; Giacca, A
Link:	Full Text Finder (Volltext)
Zeitschrift:	Cell metabolism, Jg. 33 (2021-04-06), Heft 4, S. 709-720
Veröffentlichung:	Cambridge, Mass. : Cell Press, c2005-, 2021
Medientyp:	academicJournal
ISSN:	1932-7420 (electronic)
DOI:	10.1016/j.cmet.2021.03.007
Schlagwort:	Adipose Tissue metabolism Animals Central Nervous System drug effects Central Nervous System metabolism Fatty Acids, Nonesterified metabolism Gluconeogenesis Humans Insulin pharmacology Liver drug effects Signal Transduction Glucose metabolism Insulin metabolism Liver metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Review Language: English [Cell Metab] 2021 Apr 06; Vol. 33 (4), pp. 709-720. <i>Date of Electronic Publication: </i>2021 Mar 24. MeSH Terms: Glucose / metabolism ; Insulin / metabolism ; Liver / *metabolism ; Adipose Tissue / metabolism ; Animals ; Central Nervous System / drug effects ; Central Nervous System / metabolism ; Fatty Acids, Nonesterified / metabolism ; Gluconeogenesis ; Humans ; Insulin / pharmacology ; Liver / drug effects ; Signal Transduction Grant Information: PJT-153301 Canada CIHR; PJT-341582 Canada CIHR; PJT-299962 Canada CIHR; PJT-153032 Canada CIHR; PJT-166061 Canada CIHR; PJT-201610 Canada CIHR; PJT-201909 Canada CIHR Contributed Indexing: Keywords: central nervous system; free fatty acids; glucagon; glucose; hepatic; insulin; portal vein Substance Nomenclature: 0 (Fatty Acids, Nonesterified) ; 0 (Insulin) ; IY9XDZ35W2 (Glucose) Entry Date(s): Date Created: 20210325 Date Completed: 20220125 Latest Revision: 20220125 Update Code: 20231215

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