Original Data

Expression Analysis of cPLA2 Alpha Interacting TIP60 in Diabetic KKAy and Non-Diabetic C57BL Wild-Type Mice: No Impact of Transient and Stable TIP60 Overexpression on Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells

Iver Nordentoft¹, Per B. Jeppesen¹, Anders L. Nielsen², Poul Jorgensen³, Kjeld Hermansen¹

Keywords: type 2 diabetes, beta-cell, TIP60, MIN6 cell, INS-1E cell, gene expression

Abstract

In the present study we investigate the expression levels of cytosolic phospholipase A₂ α (cPLA2α) interacting histone acetyl transferase proteins TIP60α and TIP60β 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 β-cells. MATERIAL AND METHODS: 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 TIP60α and TIP60β on glucose-stimulated insulin secretion by transient and stable overexpression in the pancreatic mouse β-cell line MIN6 and the rat β-cell line INS-1E. RESULTS: We found that non-diabetic C57BL mice and diabetic KKAy mice have the same level of both the α and β 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. CONCLUSION: TIP60 over-expression does not affect glucose stimulated insulin secretion, insulin content or abnormal β-cell function during glucotoxicity.

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