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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Hepatobiliary Diseases and Insulin Resistance

Author(s): Nahum Mendez-Sanchez, Noberto C. Chavez-Tapia, D. Zamora-Valdes, Roberto Medina-Santillan and Misael Uribe

Volume 14, Issue 18, 2007

Page: [1988 - 1999] Pages: 12

DOI: 10.2174/092986707781368540

Price: $65


In recent years, there has been an increasing prevalence of obesity and related diseases. This epidemiological change has increased the interest of researchers in the molecular and biochemical pathways involved in the pathogenesis of hepatic and biliary diseases. Insulin resistance is considered the major mechanism involved in the hepatic and biliary manifestations of obesity. Epidemiological, clinical, and basic research demonstrates that insulin resistance is associated with gallstone disease, nonalcoholic fatty liver disease, and poor outcomes in viral hepatitis C treatments. Fascinating experimental evidence demonstrates that fat-induced hepatic insulin resistance may result from the activation of kinases leading to impaired insulin signaling. The insulin-resistant state is characterized by a failure to suppress hepatic glucose production and glycogenolysis, with enhanced fat accumulation in hepatocytes because of increased lipolysis, increased free fatty acid uptake by hepatocytes, and increased hepatic synthesis of triglycerides. This molecular signaling induces a low-grade chronic inflammatory state, characterized by increased levels of proinflammatory molecules and acute-phase proteins. This review summarizes the most important molecular and biochemical issues in the hepatic and biliary diseases associated with insulin resistance.

Keywords: Insulin resistance, gallstone disease, nonalcoholic fatty liver disease, hepatocellular carcinoma, obesity, metabolic syndrome

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