| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Endocrinology and Diabetes, St. Thomas’ Hospital, GKT School of Medicine (H.L.S., N.C.J., F.S.-M., R.H.J., P.H.S., A.M.U.), London, United Kingdom SE1 7EH; Department of Pediatrics, University of Cambridge, Addenbrooke’s Hospital (D.B.D.), Cambridge, United Kingdom CB2 2QQ; and Department of Diabetes and Endocrinology, Royal Surrey County Hospital (D.L.R.-J.), Guildford, Surrey, United Kingdom GU2 5XX
Address all correspondence and requests for reprints to: Dr. Helen Simpson, Department of Endocrinology and Diabetes, St. Thomas’ Hospital, GKT School of Medicine, London, United Kingdom SE1 7EH. E-mail: helen.simpson{at}kcl.ac.uk.
There is evidence of a metabolic role for IGF-I in type 1 diabetes, but it is unclear whether IGF-I acts indirectly by reducing GH secretion or has direct effects. Using stable isotopes we have investigated, on three separate occasions, the effect of a pulse of recombinant human GH, a sc injection of recombinant human IGF-I, and a placebo on glucose, lipid, and protein metabolism in subjects with type 1 diabetes during a basal insulin infusion and a hyperinsulinemic euglycemic clamp. Endogenous GH secretion was suppressed with octreotide. IGF-I reduced the hepatic glucose production rate (Ra), increased peripheral glucose uptake, and reduced protein breakdown during the basal insulin infusion (P < 0.05, P < 0.005, and P < 0.05, respectively, vs. placebo) and the hyperinsulinemic euglycemic clamp (P < 0.05, P < 0.005, and P < 0.05, respectively, vs. placebo). IGF-I had no effect on glycerol Ra, an index of lipolysis. GH increased glucose and glycerol Ra during the basal insulin infusion (P < 0.005 vs. placebo study), but the effects were no different from placebo during the clamp. In conclusion, IGF-I had a direct effect on glucose and protein metabolism, which was maintained during the hyperinsulinemic euglycemic clamp. This suggests that IGF-I acts in concert with insulin and may have an important role in maintaining glucose homeostasis and protein metabolism in type 1 diabetes.
This work was supported by a fellowship from the Guys and St. Thomas’ Charitable Foundation.
Abbreviations: CV, Coefficient of variation; 
-KIC, -ketoisocaproate; MCR, metabolic clearance rate; NEFA, nonesterified fatty acids; NOLD, nonoxidative leucine disposal; Ra, production rate; Rd, rate of uptake; rh, recombinant human.
This article has been cited by other articles:
 |
|
 |
|
  B. Salgin, M. L. Marcovecchio, R. M. Williams, S. J. Jackson, L. J. Bluck, S. M. Humphreys, C. L. Acerini, and D. B. Dunger Effects of Growth Hormone and Free Fatty Acids on Insulin Sensitivity in Patients with Type 1 Diabetes J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3297 - 3305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ohlsson, S. Mohan, K. Sjogren, A. Tivesten, J. Isgaard, O. Isaksson, J.-O. Jansson, and J. Svensson The Role of Liver-Derived Insulin-Like Growth Factor-I Endocr. Rev., August 1, 2009; 30(5): 494 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Higham, S. Rowles, D. Russell-Jones, A. M. Umpleby, and P. J. Trainer Pegvisomant Improves Insulin Sensitivity and Reduces Overnight Free Fatty Acid Concentrations in Patients with Acromegaly J. Clin. Endocrinol. Metab., July 1, 2009; 94(7): 2459 - 2463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Robertson, Y. Lu, K. De Jesus, B. Li, Q. Su, P. K. Lund, and J.-L. Liu A general and islet cell-enriched overexpression of IGF-I results in normal islet cell growth, hypoglycemia, and significant resistance to experimental diabetes Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E928 - E938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. F. Collett-Solberg, M. Misra, and on behalf of the Drug and Therapeutics Committee o The Role of Recombinant Human Insulin-Like Growth Factor-I in Treating Children with Short Stature J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 10 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Maggio, F. Lauretani, G. P. Ceda, S. Bandinelli, S. M. Ling, E. J. Metter, A. Artoni, L. Carassale, A. Cazzato, G. Ceresini, et al. Relationship Between Low Levels of Anabolic Hormones and 6-Year Mortality in Older Men: The Aging in the Chianti Area (InCHIANTI) Study Arch Intern Med, November 12, 2007; 167(20): 2249 - 2254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Morimoto, R. Nishimura, T. Matsudaira, H. Sano, N. Tajima, and for the Diabetes Epidemiology Research Internation Is Pubertal Onset a Risk Factor for Blindness and Renal Replacement Therapy in Childhood-Onset Type 1 Diabetes in Japan? Diabetes Care, September 1, 2007; 30(9): 2338 - 2340. [Full Text] [PDF]
|
|
|
|
 |
|
 E M Delemarre, J Rotteveel, and H A D.-v. de Waal Metabolic implications of GH treatment in small for gestational age Eur. J. Endocrinol., August 1, 2007; 157(suppl_1): S47 - S50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. McDonald, R. M Williams, F. M Regan, R. K Semple, and D. B Dunger IGF-I treatment of insulin resistance Eur. J. Endocrinol., August 1, 2007; 157(suppl_1): S51 - S56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ekstrom, J. Salemyr, I. Zachrisson, C. Carlsson-Skwirut, E. Ortqvist, and P. Bang Normalization of the IGF-IGFBP Axis by Sustained Nightly Insulinization in Type 1 Diabetes Diabetes Care, June 1, 2007; 30(6): 1357 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Denley, J. M. Carroll, G. V. Brierley, L. Cosgrove, J. Wallace, B. Forbes, and C. T. Roberts Jr. Differential Activation of Insulin Receptor Substrates 1 and 2 by Insulin-Like Growth Factor-Activated Insulin Receptors Mol. Cell. Biol., May 15, 2007; 27(10): 3569 - 3577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Muzumdar, X. Ma, S. Fishman, X. Yang, G. Atzmon, P. Vuguin, F. H. Einstein, D. Hwang, P. Cohen, and N. Barzilai Central and Opposing Effects of IGF-I and IGF-Binding Protein-3 on Systemic Insulin Action. Diabetes, October 1, 2006; 55(10): 2788 - 2796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Saukkonen, F. Shojaee-Moradie, R. M. Williams, R. Amin, K. C. Yuen, A. Watts, C. L. Acerini, A. M. Umpleby, and D. B. Dunger Effects of Recombinant Human IGF-I/IGF-Binding Protein-3 Complex on Glucose and Glycerol Metabolism in Type 1 Diabetes. Diabetes, August 1, 2006; 55(8): 2365 - 2370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E Street, M. A Ziveri, C. Spaggiari, I. Viani, C. Volta, G. L. Grzincich, R. Virdis, and S. Bernasconi Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis Eur. J. Endocrinol., January 1, 2006; 154(1): 47 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sesti, A. Sciacqua, M. Cardellini, M. A. Marini, R. Maio, M. Vatrano, E. Succurro, R. Lauro, M. Federici, and F. Perticone Plasma Concentration of IGF-I Is Independently Associated With Insulin Sensitivity in Subjects With Different Degrees of Glucose Tolerance Diabetes Care, January 1, 2005; 28(1): 120 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Saukkonen, R. Amin, R. M. Williams, C. Fox, K. C. Yuen, M. A. White, A. M. Umpleby, C. L. Acerini, and D. B. Dunger Dose-Dependent Effects of Recombinant Human Insulin-Like Growth Factor (IGF)-I/IGF Binding Protein-3 Complex on Overnight Growth Hormone Secretion and Insulin Sensitivity in Type 1 Diabetes J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4634 - 4641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yuen, J. Frystyk, M. Umpleby, L. Fryklund, and D. Dunger Changes in Free Rather Than Total Insulin-Like Growth Factor-I Enhance Insulin Sensitivity and Suppress Endogenous Peak Growth Hormone (GH) Release following Short-Term Low-Dose GH Administration in Young Healthy Adults J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3956 - 3964. [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 |
