| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
The Department of Medicine (M.C., F.L.H., C.R., F.A.), University of Melbourne, Parkville, Melbourne, Victoria 3052; and the Department of Endocrinology and Diabetes (F.L.H., M.O., C.R., F.A.), St. Vincent’s Hospital, Fitzroy, Melbourne, Victoria 3065, Australia.
Address all correspondence and requests for reprints to: M. Christopher, Department of Endocrinology and Diabetes, St. Vincent’s Hospital, Victoria Parade, Fitzroy, Victoria 3065, Australia.
We have previously reported that GH-deficient (GHD) adults are severely
insulin resistant. In the present study, we determined the effects of 6
months (n = 7) and 24 months (long-term; n = 11) of
recombinant human GH (rhGH) therapy (
0.22 IU/kg.week) on body
composition and fasting biochemical (including lipid) parameters, and
baseline and insulin-stimulated: 1) rates of hepatic glucose
production, total glucose disposal (Rd), total glycolysis (GF) and
glucose storage (GS); and 2) skeletal muscle glucose processing [using
the euglycemic-hyperinsulinemic (60 mU/L) clamp technique with
tritiated glucose infusion coupled with skeletal muscle biopsies]. To
allow baseline comparison, these measurements were also obtained from
10 control subjects matched to the pretreated GHD adults for age, sex,
and body mass index. Long-term rhGH therapy in GHD adults induced
significant improvements in fat mass, abdominal fat mass and fat free
mass, and reductions in fasting cholesterol and low-density
lipoprotein-cholesterol levels (P < 0.05–0.01
vs. pretreatment values). However, there was a
significant increase in fasting insulin (13.1 ± 0.9
vs. 8.6 ± 1.1 mU/L; P < 0.01)
and connecting peptide (0.56 ± 0.05 vs. 0.41
± 0.06 nmol/L; P < 0.05). Although rates of
baseline hepatic glucose production, GF, and GS were unchanged, the
insulin-stimulated increment (
) in Rd, GF, and GS remained markedly
attenuated in the long-term rhGH-treated GHD adults [pretreatment:
Rd 16.6 ± 3.4, GF 3.0 ± 1.2, GS 13.6 ± 3.0
vs. 24 months of rhGH: Rd 17.2 ± 3.3, GF
3.1 ± 0.9, GS 14.1 ± 2.5 vs. controls:
Rd 42.6 ± 4.3, GF 9.2 ± 1.9, GS 35.9 ± 4.5
µmol/kg fat free mass·min; P < 0.05–0.01
vs. controls]. Additionally, there was a sustained
reduction in the insulin-stimulated skeletal muscle glycogen synthase
fractional velocity (pretreatment: 0.29 ± 0.03 vs.
24 months of rhGH: 0.24 ± 0.03 vs. controls:
0.48 ± 0.04; both P < 0.05
vs. controls), which was accompanied by a sustained 44%
decrease in baseline glycogen content and a 70% increase in baseline
im glucose concentrations in the presence of low-to-normal glucose
6-phosphate levels and persisting euglycemia. Stepwise regression
analysis revealed that body weight and fasting free fatty acid and
high-density lipoprotein (HDL)-cholesterol accounted for 82% of the
variance in the insulin sensitivity index in long-term rhGH-treated
adults, and that the 24-month fasting insulin-like growth factor 1 was
a negative predictor of the change in insulin sensitivity (r =
-0.82; P < 0.01). In conclusion, despite
improvements in body composition and lipid profiles, the severe defects
of in vivo insulin sensitivity and skeletal muscle
intracellular glucose phosphorylation and glycogen synthase activity,
which are associated with modestly elevated insulin-like growth factor
1 levels, normal free fatty acid levels, and the development of
hyperinsulinemia, persist with long-term rhGH therapy.
This article has been cited by other articles:
 |
|
 |
|
  N. Moller and J. O. L. Jorgensen Effects of Growth Hormone on Glucose, Lipid, and Protein Metabolism in Human Subjects Endocr. Rev., April 1, 2009; 30(2): 152 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Jang, V. R Obeyesekere, F. P Alford, and W. J Inder Skeletal muscle 11{beta} hydroxysteroid dehydrogenase type 1 activity is upregulated following elective abdominal surgery Eur. J. Endocrinol., February 1, 2009; 160(2): 249 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Jang, V. R. Obeyesekere, R. J. Dilley, Z. Krozowski, W. J. Inder, and F. P. Alford Altered Activity of 11{beta}-Hydroxysteroid Dehydrogenase Types 1 and 2 in Skeletal Muscle Confers Metabolic Protection in Subjects with Type 2 Diabetes J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3314 - 3320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sjogren, K.-C. Leung, W. Kaplan, M. Gardiner-Garden, J. Gibney, and K. K. Y. Ho Growth hormone regulation of metabolic gene expression in muscle: a microarray study in hypopituitary men Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E364 - E371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Krag, L. C. Gormsen, Z. Guo, J. S. Christiansen, M. D. Jensen, S. Nielsen, and J. O. L. Jorgensen Growth hormone-induced insulin resistance is associated with increased intramyocellular triglyceride content but unaltered VLDL-triglyceride kinetics Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E920 - E927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. O. L. Jorgensen, N. Jessen, S. B. Pedersen, E. Vestergaard, L. Gormsen, S. A. Lund, and N. Billestrup GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E899 - E905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Svensson, H. Herlitz, P.-A. Lundberg, and G. Johannsson Adiponectin, Leptin, and Erythrocyte Sodium/Lithium Countertransport Activity, But Not Resistin, Are Related to Glucose Metabolism in Growth Hormone-Deficient Adults J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2290 - 2296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Svensson and B.-A. Bengtsson Growth Hormone Replacement Therapy and Insulin Sensitivity J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1453 - 1454. [Full Text] [PDF]
|
|
|
|
|
|
M. Bramnert, M. Segerlantz, E. Laurila, J. R. Daugaard, P. Manhem, and L. Groop Growth Hormone Replacement Therapy Induces Insulin Resistance by Activating the Glucose-Fatty Acid Cycle J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1455 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. Isley Growth Hormone Therapy for Adults: Not Ready for Prime Time? Ann Intern Med, August 6, 2002; 137(3): 190 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ezzat, S. Fear, R.-C. Gaillard, C. Gayle, H. Landy, S. Marcovitz, T. Mattioni, S. Nussey, A. Rees, and E. Svanberg Gender-Specific Responses of Lean Body Composition and Non-Gender-Specific Cardiac Function Improvement after GH Replacement in GH-Deficient Adults J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2725 - 2733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Svensson, J. Fowelin, K. Landin, B.-A. Bengtsson, and J.-O. Johansson Effects of Seven Years of GH-Replacement Therapy on Insulin Sensitivity in GH-Deficient Adults J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2121 - 2127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Segerlantz, M. Bramnert, P. Manhem, E. Laurila, and L. C. Groop Inhibition of the Rise in FFA by Acipimox Partially Prevents GH-Induced Insulin Resistance in GH-Deficient Adults J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5813 - 5818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Muller, F. W. G. Leebeek, J. A. M. J. L. Janssen, S. W. J. Lamberts, L. Hofland, and A. J. van der Lely Acute Effect of Pegvisomant on Cardiovascular Risk Markers in Healthy Men: Implications for the Pathogenesis of Atherosclerosis in GH Deficiency J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5165 - 5171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. McConnell, A. B. Atkinson, C. Ennis, D. R. Hadden, D. R. McCance, B. Sheridan, and P. M. Bell The Effects on Insulin Action in Adult Hypopituitarism of Recombinant Human GH Therapy Individually Titrated for Six Months J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5342 - 5347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gotherstrom, J. Svensson, J. Koranyi, M. Alpsten, I. Bosaus, B.-A. Bengtsson, and G. Johannsson A Prospective Study of 5 Years of GH Replacement Therapy in GH-Deficient Adults: Sustained Effects on Body Composition, Bone Mass, and Metabolic Indices J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4657 - 4665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Ahmad, R. Guzder, A. M. Wallace, J. Thomas, W. D. Fraser, and J. P. Vora Circadian and Ultradian Rhythm and Leptin Pulsatility in Adult GH Deficiency: Effects of GH Replacement J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3499 - 3506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Rosenfalck, S. Maghsoudi, S. Fisker, J. O. L. Jørgensen, J. S. Christiansen, J. Hilsted, A. Vølund, and S. Madsbad The Effect of 30 Months of Low-Dose Replacement Therapy with Recombinant Human Growth Hormone (rhGH) on Insulin and C-Peptide Kinetics, Insulin Secretion, Insulin Sensitivity, Glucose Effectiveness, and Body Composition in GH-Deficient Adults J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4173 - 4181. [Abstract] [Full Text]
|
|
|
|
|
|
K. Cusi and R. DeFronzo Recombinant Human Insulin-Like Growth Factor I Treatment for 1 Week Improves Metabolic Control in Type 2 Diabetes by Ameliorating Hepatic and Muscle Insulin Resistance J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3077 - 3084. [Abstract] [Full Text]
|
|
|
|
|
|
H. E. Botker, H. Wiggers, M. Bottcher, J. S. Christiansen, T. T. Nielsen, A. Gjedde, and O. Schmitz Short-term effects of growth hormone on myocardial glucose uptake in healthy humans Am J Physiol Endocrinol Metab, June 1, 2000; 278(6): E1053 - E1059. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
