Journal
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Volume 7, Issue 2, Pages 447-456Publisher
ELSEVIER INC
DOI: 10.1016/j.jcmgh.2018.10.016
Keywords
Insulin Signaling; Hepatic Insulin Resistance; PI3K/Akt Signaling Pathway; Hepatic Glucose Production; De Novo Lipogenesis; Metabolism
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Funding
- National Institutes of Health [K01 DK111715, P30 DK19525]
- Perelman School of Medicine at the University of Pennsylvania (P.M.T)
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This review describes the signaling pathways involved in the regulation of liver metabolism by insulin. In addition, it explores the molecular mechanisms underlying hepatic insulin resistance, highlighting the contribution of intrahepatic and extrahepatic pathways. Insulin resistance is associated with numerous metabolic disorders, such as obesity and type II diabetes, that currently plague our society. Although insulin normally promotes anabolic metabolism in the liver by increasing glucose consumption and lipid synthesis, insulin-resistant individuals fail to inhibit hepatic glucose production and paradoxically have increased liver lipid synthesis, leading to hyperglycemia and hypertriglyceridemia. Here, we detail the intrahepatic and extrahepatic pathways mediating insulin's control of glucose and lipid metabolism. We propose that the interplay between both of these pathways controls insulin signaling and that mis-regulation between the 2 results in the paradoxic effects seen in the insulin-resistant liver instead of the commonly proposed deficiencies in particular branches of only the direct hepatic pathway.
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