Every time I try to use the aforementioned keyboard shortcuts, LyX says "Command Disabled". How do I activate these shortcuts?
By default Ctrl+I may be set to "inset-toggle" which in regular use doesn't apply, while Ctrl+U should be set to "font-underline" (as is Alt+C U).
You are able to change the key binding sequences to suit your needs. Under Tools > Preferences > Editing > Shortcuts, activate the keys that you're interested in using as shortcut combinations. Specifically, find "font-ital" and "font-underline" under Font, Layouts and Textclasses:
If a bind is already used elsewhere, you can overwrite this to suit your personal needs.