---
title: "Insulin/IGF Signaling in Pancreatic Islets: Roles in Islet Biology and Therapeutic Implications"
id: "pubmed-42159041"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42159041"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42159041/"
doi: "10.1210/endrev/bnag014"
published_at: "2026-09-16T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Insulin/IGF Signaling in Pancreatic Islets: Roles in Islet Biology and Therapeutic Implications
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42159041
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42159041/)
- **DOI:** [10.1210/endrev/bnag014](https://doi.org/10.1210%2Fendrev%2Fbnag014)
- **Published At:** 2026-09-16T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The pancreatic islet (islet of Langerhans) is an endocrine organ that secretes multiple hormones coordinating human energy metabolism. Growth factors regulate functional **islet** mass to support whole-body glucose homeostasis. - A substantial body of evidence positions **insulin** and **insulin-like growth factors (IGFs)** as central modulators of diverse aspects of **islet cell biology**, with dysregulated **insulin/IGF signaling** recognized as a pathophysiological hallmark of type 2 diabetes. - Recent reports, particularly focused on **β-cells**, describe emerging mechanisms in insulin/IGF action including roles for **RNA modifications**, transcriptional regulation by **nuclear insulin and IGF-1 receptors**, and the identification of an inhibitory receptor termed **inceptor**. - The review summarizes functional roles of insulin/IGF signaling in regulating islet cell biology, considers both short- and long-term effects of **insulin therapy** in humans, and discusses potential strategies to maximize beneficial insulin action within islets to counter diabetes. - Keywords emphasized in the source include **diabetes**, **human pancreatic islet/β-cell**, **inceptor**, **incretins**, **insulin therapy**, and **insulin/IGF signaling**. The work is a 2026 review by Hyunki Kim and Rohit N Kulkarni in Endocrine Reviews (PMID 42159041, DOI 10.1210/endrev/bnag014).
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA 02115, USA. * 2 Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. * 3 Harvard Stem Cell Institute, Harvard Medical School, Cambridge, MA 02138, USA. * PMID: **42159041** * DOI: [ 10.1210/endrev/bnag014 ](https://doi.org/10.1210/endrev/bnag014) Free article Item in Clipboard Review # Insulin/IGF signaling in islet biology and its therapeutic implications Hyunki Kim et al. Endocr Rev. 2026. Free article Show details Display options Display options Format Abstract PubMed PMID Endocr Rev Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Endocr+Rev%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Endocr+Rev%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) . 2026 Sep 16;47(5):637-665. doi: 10.1210/endrev/bnag014. ### Authors [Hyunki Kim](https://pubmed.ncbi.nlm.nih.gov/?term=Kim+H&cauthor_id=42159041)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42159041/#short-view-affiliation-1 "Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA 02115, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42159041/#short-view-affiliation-2 "Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42159041/#short-view-affiliation-3 "Harvard Stem Cell Institute, Harvard Medical School, Cambridge, MA 02138, USA."), [Rohit N Kulkarni](https://pubmed.ncbi.nlm.nih.gov/?term=Kulkarni+RN&cauthor_id=42159041)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42159041/#short-view-affiliation-1 "Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA 02115, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42159041/#short-view-affiliation-2 "Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42159041/#short-view-affiliation-3 "Harvard Stem Cell Institute, Harvard Medical School, Cambridge, MA 02138, USA.") ### Affiliations * 1 Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA 02115, USA. * 2 Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. * 3 Harvard Stem Cell Institute, Harvard Medical School, Cambridge, MA 02138, USA. * PMID: **42159041** * DOI: [ 10.1210/endrev/bnag014 ](https://doi.org/10.1210/endrev/bnag014) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract The islet of Langerhans (or pancreatic islet) is a unique endocrine organ that secretes multiple hormones that in turn orchestrate energy metabolism in humans. As in other metabolic organs, growth factor(s) regulate functional islet mass to maintain whole-body glucose homeostasis. Over the past decades, a large body of evidence has pointed to insulin and insulin-like growth factors (IGFs) as playing central roles in modulating diverse aspects of islet cell biology and a dysregulated insulin/IGF pathway has come to be recognized as a pathophysiological hallmark of type 2 diabetes. Several recent reports, especially focused on β-cells, highlight emerging aspects of insulin/IGF signaling, including a role for RNA modifications, transcriptional regulation by nuclear insulin and IGF-1 receptors, and the discovery of an insulin inhibitory receptor, inceptor. In this review, we summarize the functional roles of insulin/IGF signaling in regulating islet cell biology, the short- and long-term effects of insulin therapy in humans, and propose potential strategies to maximize the beneficial effects of insulin action in islets to counter diabetes. **Keywords:** diabetes; human pancreatic islet/β-cell; inceptor; incretins; insulin therapy; insulin/IGF signaling. © The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Cited by * [ Lipid Metabolic Disorders: a Pivotal Driver in Type 2 Diabetes Mellitus Pathogenesis. ](https://pubmed.ncbi.nlm.nih.gov/42366306/) Wu J, Wang H, Fu M, Zhang M, Zhao G, Yu B.Wu J, et al.Curr Obes Rep. 2026 Jun 29;15(1):53. doi: 10.1007/s13679-026-00732-5.Curr Obes Rep. 2026.PMID: 42366306Free PMC article.Review. ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) * Diabetes Mellitus, Type 2* / drug therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetes+Mellitus%2C+Type+2%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetes+Mellitus%2C+Type+2) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) * Diabetes Mellitus, Type 2* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetes+Mellitus%2C+Type+2%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetes+Mellitus%2C+Type+2) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) * Insulin* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Insulin%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Insulin) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) * Insulin* / therapeutic use Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Insulin%2Ftherapeutic+use%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Insulin) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) * Insulin-Like Peptides* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Insulin-Like+Peptides%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Insulin-Like+Peptides) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) * Islets of Langerhans* / drug effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Islets+of+Langerhans%2Fdrug+effects%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Islets+of+Langerhans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) * Islets of Langerhans* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Islets+of+Langerhans%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Islets+of+Langerhans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) * Signal Transduction* / physiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Signal+Transduction%2Fphysiology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Signal+Transduction) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) * Somatomedins* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Somatomedins%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Somatomedins) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42159041/) ## 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