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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
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The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Factors affecting insulin-regulated hepatic gene expression.

Hong-Ping Guan1, Guoxun Chen2

  • 1Department of Diabetes, Merck Research Laboratories, Kenilworth, New Jersey, USA.

Progress in Molecular Biology and Translational Science
|December 31, 2013
PubMed
Summary

Insulin resistance impairs liver metabolism, altering gene expression crucial for glucose and fatty acid balance. This review details how diet, drugs, and hormones impact insulin-regulated hepatic gene expression, offering insights into metabolic disease mechanisms.

Keywords:
DiabetesFatty acid synthesisGluconeogenesisInsulin resistanceLiver steatosisTranscriptional regulation

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Area of Science:

  • Metabolic Regulation
  • Hepatology
  • Molecular Endocrinology

Background:

  • Obesity and noninsulin-dependent diabetes mellitus are linked to insulin resistance, a condition where insulin's physiological response is diminished.
  • Insulin critically regulates hepatic gene expression, controlling glucose and fatty acid metabolism.
  • Insulin resistance in the liver disrupts the normal suppression of gluconeogenesis while maintaining fatty acid synthesis induction.

Purpose of the Study:

  • To summarize recent advancements in understanding the effects of various factors on insulin-regulated hepatic gene expression.
  • To focus on findings specific to the liver and hepatocytes.
  • To elucidate mechanisms of insulin action and resistance in hepatic gene regulation.

Main Methods:

  • Review of extensive research on insulin signal transduction pathways in the liver.
  • Analysis of factors influencing insulin-regulated hepatic gene expression, including dietary components, drugs, hormones, and cytokines.
  • Examination of specific insulin-regulated genes (e.g., glucokinase, sterol regulatory element-binding protein-1c, cytosolic phosphoenolpyruvate carboxyl kinase) and regulatory elements.

Main Results:

  • Identification of numerous components within insulin signal transduction pathways.
  • Revelation of factors that modulate these pathways and alter insulin-regulated hepatic gene expression.
  • Proposed mechanisms underlying the effects of various factors on hepatic gene expression.

Conclusions:

  • Dietary factors, drugs, bioactive compounds, hormones, and cytokines significantly influence insulin-regulated hepatic gene expression.
  • Understanding these modulations is key to addressing metabolic disorders associated with insulin resistance.
  • Further research into these mechanisms can reveal future therapeutic strategies for liver-related metabolic diseases.