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Given super(cls, obj), cls needs to be somewhere in type(obj).__mro__. Thus the implementation checks PyType_IsSubtype instead of the more generic PyObject_IsSubclass. 
In this case int's MRO is unrelated to numbers.Number:
 >>> print(*int.__mro__, sep='\n')
 <class 'int'>
 <class 'object'>
It gets registered as a subclass via numbers.Integral.register(int).
 >>> print(*numbers.Integral._abc_registry)
 <class 'int'>
issubclass calls PyObject_IsSubclass, which uses the __subclasscheck__ API. In this case ABCMeta.__subclasscheck__ recursively checks the registry and caches the result to speed up future checks.
 >>> numbers.Number.__subclasscheck__(int)
 True
 >>> print(*numbers.Number._abc_cache)
 <class 'int'>