Submitted on August 20, 2003
Accepted on February 16, 2004
Glucose homeostasis in abdominal obesity: hepatic hyperresponsiveness to growth hormone action
M. M. Buijs1, J. A. Romijn2, J. Burggraaf3, M. L. de Kam3, M. Frolich1, M. T. Ackermans4, H. P. Sauerwein5, A. F. Cohen3, A. E. Meinders1, and H. Pijl1*
1 Department of General Internal Medicine, Leiden University Medical Centre, Leiden, The Netherlands
2 Department of Endocrinology, Leiden University Medical Centre, Leiden, The Netherlands
3 Center for Human Drug Research, Leiden University Medical Centre, Leiden, The Netherlands
4 Department of Clinical Chemistry, Laboratory of Endocrinology and Radiochemistry, Amsterdam, The Netherlands
5 Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: h.pijl{at}lumc.nl.
It has been suggested that (abdominally) obese individuals are hypersensitive to growth
hormone (GH) action. Because GH affects glucose metabolism, this may impact glucose
homeostasis in abdominal obesity. Therefore, we studied the effect of GH on glucose metabolism
in abdominally obese (OB) and normal weight (NW) premenopausal women.
An 1-h iv infusion of GH or placebo was randomly administered to six NW (body mass index
(BMI): 21.1 ± 1.9 kg/m2) and six OB (BMI: 35.5 ± 1.5 kg/m2) women in a crossover design.
Insulin, glucagon and GH secretion were suppressed by concomitant infusion of somatostatin.
Glucose kinetics were measured using a 10-h infusion of [6,6-2H2]-glucose.
In both groups, similar physiological GH peaks were reached by infusion of GH. GH strongly
stimulated endogenous glucose production (EGP) in both groups. The percentage increase was
significantly greater in OB than in NW women (29.8 ± 11.3 vs. 13.3 ± 7.4%, P = 0.014).
Accordingly, GH responsiveness, defined as the maximum response of EGP per unit GH, was
increased in OB vs. NW subjects (6.0 ± 2.1 vs. 2.2 ± 1.5 µmol.min-1.mU-1.L1, P = 0.006).
These results suggest that the liver is hyperresponsive to GH action in abdominally obese
women. The role of the somatotropic ensemble in the control of glucose homeostasis in
abdominal obesity is discussed.
