Remarkably, while control animals developed severe hyperglycaemia over the course of 10 weeks and displayed substantial insulin resistance, hyperinsulinemia and glucose intolerance at an age of 15 weeks (Fig. 3h-j), hepatic TSC22D4 knockdown (Supplementary Fig. 3k) not only prevented the onset of hyperglycaemia (Fig. 3k) but also significantly improved insulin sensitivity and insulin tolerance (Fig. 3h,i; Supplementary Fig. 3k–m) and glucose tolerance over time (Fig. 3j). Here, INS is linked to hyperinsulinism.