{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T05:01:54Z","timestamp":1794459714065,"version":"4.9.1"},"reference-count":153,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>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 \u201cprimary association\u201d. When intra-portal insulin levels are increased (e.g., obesity, Cushing\u2019s 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 \u201csecondary association\u201d 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.<\/jats:p>","DOI":"10.3389\/fendo.2024.1456195","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T04:32:37Z","timestamp":1732163557000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":48,"title":["Growth hormone\/insulin-like growth factor I axis in health and disease states: an update on the role of intra-portal insulin"],"prefix":"10.3389","volume":"15","author":[{"given":"Kevin C. 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