Diabetes and apoptosis: liver.
The liver is a central regulator of glucose homeostasis and stores or releases glucose according to metabolic demands. In insulin resistant states or diabetes the dysregulation of hepatic glucose release contributes significantly to the pathophysiology of these conditions. Acute or chronic liver disease can aggravate insulin resistance and the physiological effects of insulin on hepatocytes are disturbed. Insulin resistance has also been recognized as an independent risk factor for the development of liver injury. In the healthy liver tissue homeostasis is achieved through cell turnover by apoptosis and dysregulation of the physiological process resulting in too much or too little cell death can have potentially devastating effects on liver tissue. The delineation of the signaling pathways that mediate apoptosis changed the paradigms of understanding of many liver diseases. These signaling events include cell surface based receptor-ligand systems and intracellular signaling pathways that are regulated through kinases on multiple levels. The dissection of these signaling pathways has shown that the regulators of apoptosis signaling events in hepatocytes can also modulate insulin signaling pathways and that mediators of insulin resistance in turn influence liver cell apoptosis. This review will summarize the potential crosstalk between apoptosis and insulin resistance signaling events and discuss the involved mediators.
Schattenberg
Jörn M
JM
I. Medizinsiche Klinik, University Medical Center of the Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany. schatten@uni-mainz.de
Schuchmann
Marcus
M
D000818:Animals; D017209:Apoptosis; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction
D005947:Glucose