Hepatic insulin receptor: new views on the mechanisms of liver disease

Wang Hsin Lee; Sonia M. Najjar; C. Ronald Kahn; Terry D. Hinds

doi:10.1016/j.metabol.2023.155607

Hepatic insulin receptor: new views on the mechanisms of liver disease

Wang Hsin Lee, Sonia M. Najjar, C. Ronald Kahn, Terry D. Hinds

Research output: Contribution to journal › Review article › peer-review

37 Scopus citations

Abstract

Over 65 % of people with obesity display the metabolic-associated fatty liver disease (MAFLD), which can manifest as steatohepatitis, fibrosis, cirrhosis, or liver cancer. The development and progression of MAFLD involve hepatic insulin resistance and reduced insulin clearance. This review discusses the relationships between altered insulin signaling, hepatic insulin resistance, and reduced insulin clearance in the development of MAFLD and how this provides the impetus for exploring the use of insulin sensitizers to curb this disease. The review also explores the role of the insulin receptor in hepatocytes and hepatic stellate cells and how it signals in metabolic and end-stage liver diseases. Finally, we discuss new research findings that indicate that advanced hepatic diseases may be an insulin-sensitive state in the liver and deliberate whether insulin sensitizers should be used to manage late-stage liver diseases.

Original language	English
Article number	155607
Journal	Metabolism: Clinical and Experimental
Volume	145
DOIs	https://doi.org/10.1016/j.metabol.2023.155607
State	Published - Aug 2023

Bibliographical note

Publisher Copyright:
© 2023

Funding

This work was supported by the National Institutes of Health grant R01DK121797 (T.D.H.J.), and R01DK054254 , R01DK124126 , and R01DK129877 (S.M.N.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funders	Funder number
National Institutes of Health (NIH)	R01DK129877, R01DK054254, R01DK124126, R01DK121797
National Institutes of Health (NIH)

Keywords

Cirrhosis
Fatty liver
Hepatic stellate cells
Hepatocytes
Insulin clearance
Insulin resistance
Lipogenesis
MAFLD
MASH
NAFLD
NASH

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.metabol.2023.155607

Cite this

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title = "Hepatic insulin receptor: new views on the mechanisms of liver disease",

abstract = "Over 65 \% of people with obesity display the metabolic-associated fatty liver disease (MAFLD), which can manifest as steatohepatitis, fibrosis, cirrhosis, or liver cancer. The development and progression of MAFLD involve hepatic insulin resistance and reduced insulin clearance. This review discusses the relationships between altered insulin signaling, hepatic insulin resistance, and reduced insulin clearance in the development of MAFLD and how this provides the impetus for exploring the use of insulin sensitizers to curb this disease. The review also explores the role of the insulin receptor in hepatocytes and hepatic stellate cells and how it signals in metabolic and end-stage liver diseases. Finally, we discuss new research findings that indicate that advanced hepatic diseases may be an insulin-sensitive state in the liver and deliberate whether insulin sensitizers should be used to manage late-stage liver diseases.",

keywords = "Cirrhosis, Fatty liver, Hepatic stellate cells, Hepatocytes, Insulin clearance, Insulin resistance, Lipogenesis, MAFLD, MASH, NAFLD, NASH",

author = "Lee, \{Wang Hsin\} and Najjar, \{Sonia M.\} and Kahn, \{C. Ronald\} and Hinds, \{Terry D.\}",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = aug,

doi = "10.1016/j.metabol.2023.155607",

language = "English",

volume = "145",

}

TY - JOUR

T1 - Hepatic insulin receptor

T2 - new views on the mechanisms of liver disease

AU - Lee, Wang Hsin

AU - Najjar, Sonia M.

AU - Kahn, C. Ronald

AU - Hinds, Terry D.

PY - 2023/8

Y1 - 2023/8

N2 - Over 65 % of people with obesity display the metabolic-associated fatty liver disease (MAFLD), which can manifest as steatohepatitis, fibrosis, cirrhosis, or liver cancer. The development and progression of MAFLD involve hepatic insulin resistance and reduced insulin clearance. This review discusses the relationships between altered insulin signaling, hepatic insulin resistance, and reduced insulin clearance in the development of MAFLD and how this provides the impetus for exploring the use of insulin sensitizers to curb this disease. The review also explores the role of the insulin receptor in hepatocytes and hepatic stellate cells and how it signals in metabolic and end-stage liver diseases. Finally, we discuss new research findings that indicate that advanced hepatic diseases may be an insulin-sensitive state in the liver and deliberate whether insulin sensitizers should be used to manage late-stage liver diseases.

AB - Over 65 % of people with obesity display the metabolic-associated fatty liver disease (MAFLD), which can manifest as steatohepatitis, fibrosis, cirrhosis, or liver cancer. The development and progression of MAFLD involve hepatic insulin resistance and reduced insulin clearance. This review discusses the relationships between altered insulin signaling, hepatic insulin resistance, and reduced insulin clearance in the development of MAFLD and how this provides the impetus for exploring the use of insulin sensitizers to curb this disease. The review also explores the role of the insulin receptor in hepatocytes and hepatic stellate cells and how it signals in metabolic and end-stage liver diseases. Finally, we discuss new research findings that indicate that advanced hepatic diseases may be an insulin-sensitive state in the liver and deliberate whether insulin sensitizers should be used to manage late-stage liver diseases.

KW - Cirrhosis

KW - Fatty liver

KW - Hepatic stellate cells

KW - Hepatocytes

KW - Insulin clearance

KW - Insulin resistance

KW - Lipogenesis

KW - MAFLD

KW - MASH

KW - NAFLD

KW - NASH

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U2 - 10.1016/j.metabol.2023.155607

DO - 10.1016/j.metabol.2023.155607

M3 - Review article

C2 - 37271372

AN - SCOPUS:85161049796

SN - 0026-0495

VL - 145

JO - Metabolism: Clinical and Experimental

JF - Metabolism: Clinical and Experimental

M1 - 155607

ER -

Hepatic insulin receptor: new views on the mechanisms of liver disease

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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