According to unnamed Pakistani officials, the 2 Pakistanis shot by an American in Lahore were ISI agents. This account is disputed by the US govt. The issue is threatening to blow up US-Pakistani relations, as US congressmen warn that aid to Pak may be cut if the American staffer is not released by Pakistani authorities.
Personally, I think that suspiciously convenient suicide by the widow in protest against handing back her husband's killer looks to be rather staged. It's entirely possible that ISI convinced her to pretend to take poison, with the promise of getting her a lucrative settlement, and then killed her with real poison anyway. One can't put anything past the predatory praetorians at ISI.
Since Pakistan always responds to US pressure by burning NATO tanker convoys, then perhaps the US should adopt a similar approach by hiring Somali and Kenyan pirates. Every time a tanker convoy gets attacked in Pak, then likewise Pakistani shipping can mysteriously suffer similar attacks. If convoys can't get into Afghanistan through Pak territory, then neither should ships be allowed to get in or out of Pakistan across the high seas. Tit for tat.