Hepatic insulin resistance and altered insulin metabolism, as characterised by the desensitisation of hepatic parenchymal cells to insulin, play a role in the pathogenesis of liver disease, particularly resulting in steatosis and steatohepatitis. By the same token, type II diabetic patients are at higher risk for developing liver diseases, including steatosis, hepatitis, cirrhosis, and hepatocellular carcinoma. On the other hand, established liver disease from any cause leads to glucose intolerance and peripheral insulin resistance systemically. The link between insulin resistance and liver pathology reviewed in this book suggests that insulin resistance is closely related with a variety of liver diseases. Recent evidence indicates that the AMP activating protein kinase (AMPK) in conjunction with p70 ribosomal S6 kinase 1 (S6K1) serves as a key signalling pathway regulating insulin-dependent physiological functions; thus, this pathway serves as a target for the therapy of diseases associated with insulin resistance. In this chapter, the regulatory role of the AMPK-S6K1 pathway is discussed in terms of enhancing insulin receptor signalling with insulin receptor substrate-1/2 and phosphatidylinositol phosphate kinase activity, which may contribute to preventing and/or treating insulin resistance in the liver.

This book bridges the gap between advances in basic biology and chemistry and technological applications in the field of toxicity assessments. It describes areas of progress in the laboratory and clinic and discusses aspects of cellular organelles. It also covers the basic principles and applications of modern toxicological tools such as transcriptomic, proteomic, and metabolomic approaches. The recent developments on molecular modeling and systems biology are described with an eye on the future establishment of virtual cell technology. Finally the clinical implications for the understanding of acute and chronic renal toxicity are studied.