Glycogenin-2 is dispensable for liver glycogen synthesis and glucagon-stimulated glucose release

J Clin Endocrinol Metab. 2015 May;100(5):E767-75. doi: 10.1210/jc.2014-4337. Epub 2015 Mar 9.


Context: The synthesis of glycogen is initiated by glycogenin. In humans, glycogenin-1 is expressed ubiquitously, whereas glycogenin-2 (GN2) is highly expressed in liver. It has therefore been suggested that GN2 is a liver isoform of glycogenin. In a search for possible copy number variations associated with monogenic diabetes, we identified a 102-kb deletion of the X chromosome involving the entire GYG2 gene (encoding GN2) in 2 families.

Objective: The purpose of this study was to test whether male GYG2 deletion carriers had abnormal glucose metabolism and/or glycogen synthesis.

Design, setting, and patients: Two families with diabetes and a GYG2 deletion were investigated with medical history and examination, glucagon stimulation tests, and liver biopsies.

Results: We identified a GYG2 deletion in 3 members of family 1, 8 members of family 2, and 1 blood donor. The deletion showed no clear cosegregation with diabetes. Deletion carriers reported no symptoms related to fasting. Results of cardiac examination and abdominal ultrasound imaging were normal. A glucagon stimulation test in 4 male deletion carriers showed a mean rise in plasma glucose of 3.6 mmol/L (95% confidence interval, 2.9-4.2) compared with 2.8 mmol/L (95% confidence interval, 2.2-3.4) in control subjects. Liver biopsy specimens did not show clear morphologic changes by light microscopy and showed the presence of both α- and β-glycogen by electron microscopy. We detected GYG1 but not GYG2 mRNA expression in the liver biopsy specimens.

Conclusions: This is the first evaluation of humans without GN2 expression. Our data indicate that GN2 is not required for liver glycogen synthesis and glucagon-stimulated glucose release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Carbohydrate Metabolism / genetics
  • Female
  • Glucagon / pharmacology*
  • Glucosyltransferases / genetics*
  • Glucosyltransferases / metabolism
  • Humans
  • Liver / drug effects
  • Liver / metabolism*
  • Liver Glycogen / biosynthesis*
  • Male
  • Middle Aged


  • Blood Glucose
  • Liver Glycogen
  • Glucagon
  • Glucosyltransferases
  • GYG2 protein, human