Irene upsets him (5)
I believe the answer is:
ernie
'him' is the definition.
'irene upsets' is the wordplay.
'upsets' indicates an anagram.
'irene' with letters rearranged gives 'ERNIE'.
(Other definitions for ernie that I've seen before include "Wise fellow" , "Name given to selector" , "Wise for instance" , "Wise, perhaps" , "Premium?bond computer" .)