| Autor: |
Liu, Bo, Barbosa-Sampaio, Helena, Jones, Peter M., Persaud, Shanta J., Muller, Dany S., Tsilibary, Effie C. |
| Předmět: |
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| Zdroj: |
PLoS ONE; Sep2012, Vol. 7 Issue 9, Special section p1-9, 9p |
| Abstrakt: |
Progressive reduction in b-cell mass is responsible for the development of type 2 diabetes mellitus, and alteration in insulin receptor substrate 2 (IRS-2) abundance plays a critical role in this process. IRS-2 expression is stimulated by the transcription factor cAMP response element-binding protein (CREB) and we recently demonstrated that Ca2+/calmodulin dependent kinase 4 (CaMK4) is upstream of CREB activation in b-cells. This study investigated whether CaMK4 is also a potential target to increase β-cell mass through CREB-mediated IRS-2 expression, by quantifying mouse MIN6 β-cell proliferation and apoptosis following IRS-2 knockdown, CaMKs inhibition and alterations in CaMK4 and CREB expression. Expression of constitutively active CaMK4 (ΔCaMK4) and CREB (CREBDIEDLM) significantly stimulated β-cell proliferation and survival. In contrast, expression of their corresponding dominant negative forms (ΔK75ECaMK4 and CREBM1) and silencing of IRS-2 increased apoptosis and reduced b-cell division. Moreover, CREBDIEDLM and CREBM1 expression completely abolished the effects of ΔK75E CaMK4 and of ΔCaMK4, respectively. Our results indicate that CaMK4 regulates β-cell proliferation and apoptosis in a CREB-dependent manner and that CaMK4-induced IRS-2 expression is important in these processes. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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