Growth hormone increases intrahepatic rates of glycogen synthesis in growth hormone deficient adults

Document Type

Article

Department

Paediatrics and Child Health

Abstract

Background and aims: We have previously shown that growth hormone replacement is associated with a 40% increase in intrahepatic rates of glycogen synthesis during refeeding in children with idiopathic growth hormone deficiency. Our aims were to see whether growth hormone replacement in adults with growth hormone deficiency would be associated with a similar increase in the rates of intrahepatic glycogen synthesis and to determine whether such an increase in the rates of intrahepatic glycogen synthesis was due to increased direct uptake of glucose by the liver (direct pathway) and/or increased rates of gluconeogenesis (indirect pathway).
Materials and methods: 5 adults with growth hormone deficiency were randomly studied twice, off and on growth hormone replacement (OFF and ON, respectively). Patients were fasted overnight and then infused with glucose (15.7 ± 0.4 µmol/kg per min). Intrahepatic rates of glycogen synthesis were estimated by infusing [1-14C]galactose to steady state, administering acetaminophen, and measuring the specific activity (SA) of [14C]acetaminophen glucuronide in the urine in order to calculate steady state intrahepatic uridine diphosphate glucose (UDP-glucose) flux. The percentage of UDP-glucose coming from direct uptake of glucose was estimated by infusing [3-3 H] glucose, and measuring the SA of [3 H}acetaminophen glucuronide in the urine.
Results: Growth hormone replacement was associated with a 34 % increase in estimated rates of intrahepatic glycogen synthesis (4.42 ± 0.76 vs 5.90 ± 0.81 µmol/kg per minute for OFF and ON, respectively; p<0.05). The percentage of glucose coming from direct uptake of glucose was not affected by growth hormone treatment (44.6 ± 5.9 % vs 47.4 ± 5.8 % for OFF and ON, respectively). In summary, growth hormone treatment in growth hormone deficiency adults increased estimated rates of intrahepatic glycogen synthesis by increasing the amount of glucose entering UDP-glucose via the direct and indirect pathways equally.
Conclusion: Growth hormone appears to increase intrahepatic rates of glycogen synthesis not only by stimulating gluconeogenesis, but also by increasing direct uptake of glucose.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Diabetologia

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