INS and Hyperglycemia: Recent findings by Ashcroft et al., showed that chronic hyperglycemia increased mTORC1 signalling with concomitant reduction of AMPK signalling in β-cells, which leads to increased expression of Pdk1 that through inhibition of PDH limits the entry of pyruvate into the citric cycle and thus negatively affects oxidative phosphorylation and insulin secretion42.