Diabetes and apoptosis: lipotoxicity

Springer Science and Business Media LLC - Tập 14 - Trang 1484-1495 - 2009
Christine M. Kusminski1, Shoba Shetty1, Lelio Orci2, Roger H. Unger1, Philipp E. Scherer1,3
1Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, USA
2Faculty of Medicine, Department of Cell Physiology and Metabolism, CMU, University of Geneva, Geneva 4, Switzerland
3Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, USA

Tóm tắt

Obesity is an established risk factor in the pathogenesis of insulin resistance, type 2 diabetes mellitus and cardiovascular disease; all components that are part of the metabolic syndrome. Traditionally, insulin resistance has been defined in a glucocentric perspective. However, elevated systemic levels of fatty acids are now considered significant contributors towards the pathophysiological aspects associated with the syndrome. An overaccumulation of unoxidized long-chain fatty acids can saturate the storage capacity of adipose tissue, resulting in a lipid ‘spill over’ to non-adipose tissues, such as the liver, muscle, heart, and pancreatic-islets. Under these circumstances, such ectopic lipid deposition can have deleterious effects. The excess lipids are driven into alternative non-oxidative pathways, which result in the formation of reactive lipid moieties that promote metabolically relevant cellular dysfunction (lipotoxicity) and programmed cell-death (lipoapoptosis). Here, we focus on how both of these processes affect metabolically significant cell-types and highlight how lipotoxicity and sequential lipoapoptosis are as major mediators of insulin resistance, diabetes and cardiovascular disease.

Tài liệu tham khảo

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