Thiazolidinediones and the preservation of beta-cell function, cellular proliferation and apoptosis.
The thiazolidinediones (TZDs) or glitazones are pharmaceutical agents that have profound effects on energy expenditure and conservation. They also exert significant anti-inflammatory effects and influence cell proliferation and cell death. The drugs are primarily used in clinical practice in the treatment of patients with type 2 diabetes mellitus, a disorder of insulin resistance that occurs when the pancreatic beta-cells are unable to produce adequate amounts of insulin to maintain euglycaemia. Loss of pancreatic beta-cell function in type 2 diabetes is progressive and often precedes overt diabetes by 10 years or more, as was shown by the United Kingdom Prospective Diabetes Study. Any therapeutic or preventive approach that would limit or reverse loss of beta-cell function in diabetes would have profound effects on the morbidity associated with this widespread disease. Evidence suggesting a potential role of TZDs in preserving beta-cell function in type 2 diabetes as well as the ability of these agents to exert anti-inflammatory and proapoptotic anticancer effects, and their ability to promote cellular proliferation in various organs is reviewed.
Decker
Michael
M
Department of Medicine, University of California, Irvine Medical Center, Orange, CA 92868, USA.
Hofflich
Heather
H
Elias
Alan N
AN
D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D047495:PPAR gamma; D045162:Thiazolidinediones