Thus, considering the coexistent, enhanced insulin sensitivity in addition to the assumed compensation in Cdkal1−/− mice, it is reasonable that long-term high fat–fed intervention, i.e., 20 weeks of high-fat feeding in the present study, was required to demonstrate the exaggerated glucose intolerance by OGTT, which could result from the eventual imbalance of compensatory mechanisms. Here, INS is linked to Glucose intolerance.