Cited by 925Metabolism, Diabetes, and CancerGrowth Hormone and Insulin-like Growth FactorsPancreatic function and diabetes

IRS proteins and the common path to diabetes

White, Morris F.·2002·American Journal of Physiology-Endocrinology and Metabolism

Abstract

Although a full understanding of insulin/insulin-like growth factor (IGF) action is evolving, the discovery of insulin receptor substrate (IRS) proteins and their role to link cell surface receptors to the intracellular signaling cascades provided an important step forward. Moreover, Insulin/IGF receptors use common signaling pathways to accomplish many tasks, the IRS proteins add a unique layer of specificity and control. Importantly, the IRS-2 branch of the insulin/IGF-signaling pathway is a common element in peripheral insulin response and pancreatic β-cell growth and function. Failure of IRS-2 signaling might explain the eventual loss of compensatory hyperinsulinemia during prolonged periods of peripheral insulin resistance. Moreover, short-term inhibition of IRS protein functions by serine phosphorylation, or sustained inhibition by ubiquitin-targeted proteosome-mediated degradation suggests a common molecular mechanism for insulin resistance during acute injury or infection, or the sensitivity of β-cells to autoimmune destruction. The broad role of IRS-1 and IRS-2 in cell growth and survival reveals a common regulatory pathway linking development, somatic growth, fertility, neuronal proliferation, and aging to the core mechanisms used by vertebrates for nutrient sensing.

Integrity signals

Registry

Crossref · 10.1152/ajpendo.00514.2001

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  • IRS2 is a cytoplasmic signaling molecule that mediates the effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between receptor tyrosine kinases and downstream effectors.

    “IRS2 is a cytoplasmic signaling molecule that mediates the effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between receptor tyrosine kinases and downstream effectors (21–23).”

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Authors
White, M. F.
Affiliations
Joslin Diabetes Center (US)
Corresponding author
White, Morris F.
Venue
American Journal of Physiology-Endocrinology and Metabolism
Published
2002-09-01
Volume
283
Issue
3
Pages
E413-E422
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
OpenAlex
W2141277427
Cited by
925
References
3
Citations by year
2026: 10 · 2025: 17 · 2024: 18 · 2023: 16 · 2022: 25 · 2021: 36 · 2020: 30 · 2019: 28 · 2018: 31 · 2017: 26 · 2016: 21 · 2015: 32 · 2014: 44 · 2013: 55 · 2012: 54
FWCI
3.63
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
IRS-1, insulin receptor substrate 2, insulin/IGF signaling, insulin resistance, beta-cell function, compensatory hyperinsulinemia, serine phosphorylation, ubiquitin-proteasome degradation, nutrient sensing, diabetes mellitus, cell growth and survival
MeSH terms
Animals, Diabetes Mellitus, Growth, Humans, Insulin, Insulin Resistance, Islets of Langerhans, Longevity, Phosphoproteins, Somatomedins, Signal Transduction, Intracellular Signaling Peptides and Proteins, Insulin Receptor Substrate Proteins

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