Pancreatic beta-cell growth and survival--a role in obesity-linked type 2 diabetes?
Obesity-linked type 2 diabetes is a disease of insulin resistance combined with pancreatic beta-cell dysfunction. Although a role for beta-cell mass in the pathogenesis of obesity-linked type 2 diabetes has recently gained prominence, the idea is still being developed. It is proposed that in early obesity an increase in beta-cell mass and function might compensate for peripheral insulin resistance. However, as time and/or the severity of the obesity continue, there is decay in such adaptation and the beta-cell mass becomes inadequate. This, together with beta-cell dysfunction, leads to the onset of type 2 diabetes. It is becoming evident that elements in insulin and insulin growth factor (IGF)-1 signal-transduction pathways are key to regulating beta-cell growth. Current evidence indicates that interference of insulin signaling in obesity contributes to peripheral insulin resistance. This article examines whether a similar interference of IGF-1 signaling in the beta-cell could hinder upregulation of beta-cell mass and/or function, resulting in a failure to compensate for insulin resistance.
Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, USA.
Melissa K
MK
Lingohr
Roland
R
Buettner
Christopher J
CJ
Rhodes
D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin