Type 2 diabetes-a matter of beta-cell life and death?
In type 2 diabetes, the beta cells of the pancreas fail to produce enough insulin to meet the body's demand, in part because of an acquired decrease in beta-cell mass. In adults, pancreatic beta-cell mass is controlled by several mechanisms, including beta-cell replication, neogenesis, hypertrophy, and survival. Here, I discuss evidence supporting the notion that increased beta-cell apoptosis is an important factor contributing to beta-cell loss and the onset of type 2 diabetes. Interestingly, a key signaling molecule that promotes beta-cell growth and survival, insulin receptor substrate 2 (IRS-2), is a member of a family of proteins whose inhibition contributes to the development of insulin resistance in the liver and other insulin-responsive tissues. Thus, the IRS-2 pathway appears to be a crucial participant in the tenuous balance between effective pancreatic beta-cell mass and insulin resistance.
Rhodes
Christopher J
CJ
Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, USA. cjr@pnri.org
D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002455:Cell Division; D048429:Cell Size; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D006706:Homeostasis; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D006949:Hyperlipidemias / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D050356:Lipid Metabolism; D009765:Obesity / Q000503:physiopathology*; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction
D016207:Cytokines; C526297:IRS2 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins