Because an acetylation-mimicking mutation of GKRP (K126Q) inhibited glucose-dependent glucokinase−GKRP dissociation and diminished 2-DG uptake in mouse-derived hepatocytes, hepatic acetylation-mimicking GKRP (K126Q)-expressing mice displayed reduced hepatic 2-DG uptake and impaired glucose tolerance and resistance to NMN-dependent amelioration of the impeded hepatic 2-DG uptake and glucose intolerance in obese HFD-fed mice. The gene discussed is GCKR; the disease is Glucose intolerance.