Diabetes and apoptosis: lipotoxicity.
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.
Kusminski
Christine M
CM
Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA.
Shetty
Shoba
S
Orci
Lelio
L
Unger
Roger H
RH
Scherer
Philipp E
PE
D000818:Animals; D017209:Apoptosis; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism / Q000503:physiopathology; D050356:Lipid Metabolism; D008055:Lipids / Q000633:toxicity*; D008099:Liver / Q000503:physiopathology
D008055:Lipids