Hepatic energy metabolism in a family with a glucokinase gene mutation and dysglycemia

•Carriers heterozygous for the D124N (c.370, GAC > AAC in exon 4) variant of GCK not only exhibit reduced insulin secretion, but also impaired adipose insulin-sensitivity.•In carriers heterozygous for the D124N (c.370, GAC > AAC in exon 4) variant of GCK, impaired adipose tissue-insulin sensitivity may shift fatty acids towards the liver and thereby contribute to increased hepatic lipid accumulation and alterations of liver energy metabolism.•In carriers heterozygous for the D124N (c.370, GAC > AAC in exon 4) variant of GCK, abnormal GCK function in both beta-cells and liver, but possibly also in adipose tissue accounts for their dysglycemia. Carriers heterozygous for the D124N (c.370, GAC > AAC in exon 4) variant of GCK not only exhibit reduced insulin-secretion, but also impaired adipose insulin sensitivity, which may shift fatty acids towards the liver. This could contribute to increased hepatic lipid-accumulation and alterations of liver energy metabolism resulting in dysglycemia. ClinicalTrial.gov registration no: NCT01055093.