HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holly, J. M. P. Articles by Wass, J. A. H. Search for Related Content PubMed PubMed Citation Articles by Holly, J. M. P. Articles by Wass, J. A. H.

The insulin and growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis are two endocrine systems that are interlinked at many levels. GH is one of the glucose counter-regulatory hormones, rising in response to hypoglycaemia, it has both intrinsic hyperglycaemic actions and causes insulin resistance. Both IGF-I and its receptor have high structural and functional homology to insulin and its receptor. Insulin can regulate IGF-I production, acting on the GH receptor or at a post-receptor site. Conversely IGF-I is thought to have a permissive effect on the pancreatic insulin response to glucose.

Growth is compromised in poorly controlled diabetic children; however, a causal link with altered GH/IGF-I levels has not been proven. Insulin-dependent diabetes clearly causes derangements in the GH/IGF-I axis. In poorly controlled diabetics GH levels are invariably raised whilst normal or low levels of IGF-I are found, indicating a dissociation between the two factors. Altered IGF-binding protein levels are also found, with high levels of small binding protein and low levels of large binding protein. These derangements are probably the result of interactions at many levels although the exact mechanisms are not fully understood.

Raised GH levels could result from altered hypothalamic/pituitary control or reduced feedback inhibition. The latter could, in turn, result from low IGF-I levels, reduced availability of IGF-I to relevant receptors or increased levels of inhibitors (possibly the small binding protein). Low IGF-I levels could be directly due to deficient insulin levels or simply to lack of available circulating binding protein.

Alternative or altered molecular forms of circulating GH in diabetes seem unlikely on present evidence.

That GH has an effect on glycaemic control is most evident from the abnormal glucose tolerance seen in acromegalics, but is also seen with physiological GH variations such as during the pubertal growth spurt. In diabetics the derangements to the GH/IGF-I axis, caused by poor metabolic control, leads to aggravation of the metabolic problems.

Altered GH/IGF-I levels have been implicated in the long-term complications associated with diabetes, and whilst GH/IGF-I are not essential for the early changes involved in these complications they may still play an important role in their development, especially proliferative retinopathy.

This article has been cited by other articles:

				T. O'Connell and D. R. Clemmons IGF-I/IGF-Binding Protein-3 Combination Improves Insulin Resistance By GH-Dependent and Independent Mechanisms J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4356 - 4360. [Abstract] [Full Text] [PDF]

				L. L. Bellush, S. Doublier, A. N. Holland, L. J. Striker, G. E. Striker, and J. J. Kopchick Protection against Diabetes-Induced Nephropathy in Growth Hormone Receptor/Binding Protein Gene-Disrupted Mice Endocrinology, January 1, 2000; 141(1): 163 - 168. [Abstract] [Full Text] [PDF]

				D. T. Graves and D. L. Cochran Mesenchymal Cell Growth Factors Critical Reviews in Oral Biology & Medicine, January 1, 1990; 1(1): 17 - 36. [Full Text] [PDF]