Evaluation of glucose homeostasis revealed that 1/ the lack of α7 nAChR in 10-week-old mice leads to a reduced β-cell mass and chronic mild high glycemia without islet inflammation; 2/10-week-old α7−/− mice exhibit impaired glucose tolerance and a tendency for higher insulin sensitivity, whereas 25-week-old α7−/− mice showed both glucose intolerance and skeletal muscle insulin resistance, and 3/10 to 25-week-old α7−/− mice gained more weight through a marked increase of fat mass associated with higher food intake. Here, INS is linked to Insulin resistance.