Nordentoft Iver, Jeppesen Per B, Nielsen Anders L, Jorgensen Poul, Hermansen Kjeld
Department of Endocrinology and Metabolism C, Aarhus Sygehus THG, Aarhus University Hospital, Tage-Hansens Gade 2, DK-8000 Aarhus C, Denmark.
Rev Diabet Stud. 2007 Fall;4(3):147-58. doi: 10.1900/RDS.2007.4.147. Epub 2007 Nov 10.
In the present study we investigate the expression levels of cytosolic phospholipase A2 alpha (cPLA2alpha) interacting histone acetyl transferase proteins TIP60alpha and TIP60beta in non-diabetic C57BL wild-type mice and obese type 2 diabetic KKAy model mice. The aim was to test our hypothesis that TIP60 plays a regulatory role in glucose-stimulated insulin secretion from pancreatic beta-cells.
Ten obese diabetic KKAy mice and ten non-diabetic C57BL mice were fed a standard chow diet. After nine weeks, islet RNA was purified and used to measure TIP60 expression. We investigated the effect of TIP60alpha and TIP60beta on glucose-stimulated insulin secretion by transient and stable overexpression in the pancreatic mouse beta-cell line MIN6 and the rat beta-cell line INS-1E.
We found that non-diabetic C57BL mice and diabetic KKAy mice have the same level of both the alpha and beta splice forms of TIP60. Furthermore, we demonstrated that transient and stable expression of TIP60 in INS-1E cells affects neither glucose-stimulated insulin secretion, insulin output nor cell insulin content. Also susceptibility to developing gluco-toxicity was unaffected.
TIP60 over-expression does not affect glucose stimulated insulin secretion, insulin content or abnormal beta-cell function during glucotoxicity.
在本研究中,我们调查了非糖尿病C57BL野生型小鼠和肥胖2型糖尿病KKAy模型小鼠中,胞质磷脂酶A2α(cPLA2α)相互作用的组蛋白乙酰转移酶蛋白TIP60α和TIP60β的表达水平。目的是检验我们的假设,即TIP60在胰腺β细胞的葡萄糖刺激胰岛素分泌中起调节作用。
给10只肥胖糖尿病KKAy小鼠和10只非糖尿病C57BL小鼠喂食标准普通饲料。9周后,纯化胰岛RNA并用于测量TIP60表达。我们通过在小鼠胰腺β细胞系MIN6和大鼠β细胞系INS-1E中瞬时和稳定过表达,研究了TIP60α和TIP60β对葡萄糖刺激胰岛素分泌的影响。
我们发现非糖尿病C57BL小鼠和糖尿病KKAy小鼠中TIP60的α和β剪接形式水平相同。此外,我们证明,TIP60在INS-1E细胞中的瞬时和稳定表达既不影响葡萄糖刺激的胰岛素分泌、胰岛素产量,也不影响细胞胰岛素含量。对发生糖毒性的易感性也未受影响。
TIP60过表达不影响葡萄糖刺激的胰岛素分泌、胰岛素含量或糖毒性期间β细胞的异常功能。