Back to Search Start Over

Growth hormone/insulin-like growth factor I axis in health and disease states: an update on the role of intra-portal insulin

Authors :
Kevin C. J. Yuen
Rikke Hjortebjerg
Ashok Ainkaran Ganeshalingam
David R. Clemmons
Jan Frystyk
Source :
Frontiers in Endocrinology, Vol 15 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

Growth hormone (GH) is the key regulator of insulin-like growth factor I (IGF-I) generation in healthy states. However, portal insulin delivery is also an essential co-player in the regulation of the GH/IGF-I axis by affecting and regulating hepatic GH receptor synthesis, and subsequently altering hepatic GH sensitivity and IGF-I generation. Disease states of GH excess (e.g., acromegaly) and GH deficiency (e.g., congenital isolated GH deficiency) are characterized by increased and decreased GH, IGF-I and insulin levels, respectively, where the GH/IGF-I relationship is reflected by a “primary association”. When intra-portal insulin levels are increased (e.g., obesity, Cushing’s syndrome, or due to treatment with glucocorticoids and glucagon-like peptide 1 receptor agonists) or decreased (e.g., malnutrition, anorexia nervosa and type 1 diabetes mellitus), these changes secondarily alter hepatic GH sensitivity resulting in a “secondary association” with discordant GH and IGF-I levels (e.g., high GH/low IGF-I levels or low GH/high IGF-I levels, respectively). Additionally, intra-portal insulin regulates hepatic secretion of IGFBP-1, an inhibitor of IGF-I action. Through its effects on IGFBP-1 and subsequently free IGF-I, intra-portal insulin exerts its effects to influence endogenous GH secretion via the negative feedback loop. Therefore, it is important to understand the effects of changes in intra-portal insulin when interpreting the GH/IGF-I axis in disease states. This review summarizes our current understanding of how changes in intra-portal insulin delivery to the liver in health, disease states and drug therapy use and misuse that leads to alterations in GH/IGF-I secretion that may dictate management decisions in afflicted patients.

Details

Language :
English
ISSN :
16642392 and 86146629
Volume :
15
Database :
Directory of Open Access Journals
Journal :
Frontiers in Endocrinology
Publication Type :
Academic Journal
Accession number :
edsdoj.56562f1fe86146629b2fb6d5a7e535dc
Document Type :
article
Full Text :
https://doi.org/10.3389/fendo.2024.1456195