Cited by 733Metabolism, Diabetes, and CancerPancreatic function and diabetesAdipokines, Inflammation, and Metabolic Diseases

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Insulin Signaling in Health and Disease

White, Morris F.·2003·Science

DOI 10.1126/science.1092952

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Abstract

The signaling pathways used by insulin have been identified [M. White, Insulin Signaling Pathway, Sci. STKE (Connections Map, as seen November 2003), http://stke.sciencemag.org/cgi/cm/cmp_12069]. Now our challenge is to understand how the failure of these signals is associated with obesity and the progressive failure of pancreatic beta cells that leads to diabetes. Whether better management of chronic inflammation can improve insulin action is an important area of investigation. Drugs that stimulate IRS2 (insulin receptor substrate protein 2) synthesis or signaling might be a good starting point. This knowledge will lead to rational strategies that prevent or cure diabetes.

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The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans
Ogg, S., Paradis, S., Gottlieb, S., Patterson, G. I., Lee, L., Tissenbaum, H. A., & Ruvkun, G. (1997) · Nature · doi:10.1038/40194 · Cited by 1,935
Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
Sun, X. J., Rothenberg, P., Kahn, C. R., Backer, J. M., Araki, E., Wilden, P. A., Cahill, D. A., Goldstein, B. J., & White, M. F. (1991) · Nature · doi:10.1038/352073a0 · Cited by 1,574
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Self-citation
Insulin Receptor Isoform A, a Newly Recognized, High-Affinity Insulin-Like Growth Factor II Receptor in Fetal and Cancer Cells
Frasca, F., Pandini, G., Scalia, P., Sciacca, L., Mineo, R., Costantino, A., Goldfine, I. D., Belfiore, A., & Vigneri, R. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3278 · Cited by 897
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M. White Insulin Signaling Pathway Sci. STKE (Connections Map as seen November 2003) http://stke.sciencemag.org/cgi/cm/cmp_12069.
G. S. Hotamisligil, B. M. Spiegelman, Science259, 87 (1999).
D. L. Krebs, D. J. Hilton, Sci. STKE.2003, E6 (2003).

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“SC proliferation [308].”
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“2006; White 2003).”
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Increased insulin receptor expression in anterior temporal neocortex of patients with intractable epilepsy
Wang, L., Liu, G., He, M., Shen, L., Shen, D., Lü, Y., & Wang, X. (2010) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2010.06.005 · Cited by 9
“These signal pathways are ultimately responsible for the diverse biological effects of insulin signaling in the central nervous system, such as the inhibition of apoptosis, tau phosphorylation, the regulation of amyloid precursor protein secretion and the regulation of gene transcription [5].”
Evaluation of organ-specific glucose metabolism by 18F-FDG in insulin receptor substrate-1 (IRS-1) knockout mice as a model of insulin resistance
Cheng, C., Nakamura, A., Minamimoto, R., Shinoda, K., Tateishi, U., Goto, A., Kadowaki, T., Terauchi, Y., & Inoue, T. (2011) · Annals of Nuclear Medicine · doi:10.1007/s12149-011-0522-y · Cited by 9
“IRS-1, the major substrate of the insulin receptor, acts as an interface between the insulin receptor and intracellular signaling proteins and appears to mediate insulin/insulin-like growth factor-1 (IGF-1)-stimulated glucose transport [5–8].”
Background
Docking Assisted Prediction and Biological Evaluation of Sideritis L. Components with PTP1b Inhibitory Action and Probable Anti-Diabetic Properties
Eleftheriou, P. T., Therianou, E., Lazari, D. M., Dirnali, S., & Micha, A. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666190219104430 · Cited by 9
The jejunum is the key factor in insulin resistance
Castagneto‐Gissey, L., Angelini, G., Casella-Mariolo, J. R., Marini, P., Mingrone, G., & Casella, G. (2020) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2019.12.024 · Cited by 9
Beneficial effects of metformin on glomerular podocytes in diabetes
Rogacka, D., & Piwkowska, A. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114687 · Cited by 10
Burn injury-induced IRS-1 degradation in mouse skeletal muscle.
Lu, X.-M., Tompkins, R., & Fischman, A. J. (2013) · Europe PMC (PubMed Central) · Cited by 9
IRS2 signalling is required for the development of a subset of sensory spinal neurons
Chirivella, L., Cano‐Jaimez, M., Pérez‐Sánchez, F., Herraez, L., Carretero, J., Fariñas, I., Burks, D. J., & Kirstein, M. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07959.x · Cited by 9
“…including the inhibition of apoptosis through direct activation of the Phosphatidylinositol 3-kinase ⁄ Protein kinase B (PI3K ⁄ AKT) cascade or the Mitogen-activated protein kinase (MAPK) pathway (Alessi & Downes, 1998; Vincent & Feldman, 2002; White, 2002; White, 2003; Valverde et al., 2004).”
Background
Higher Protein Kinase C ζ in Fatty Rat Liver and Its Effect on Insulin Actions in Primary Hepatocytes
Chen, W., Goff, M. R., Kuang, H., & Chen, G. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121890 · Cited by 10
“In hepatic parenchymal cells, insulin initiates a signaling cascade upon binding to its receptor on the cell membrane, which is followed by the activation of insulin receptor substrates (IRSs) [3].”
Background
Dynamic sensitivity and control analyses of metabolic insulin signalling pathways
Liu, E., & Yuan, J. (2009) · IET Systems Biology · doi:10.1049/iet-syb.2008.0178 · Cited by 9
Clostridium butyricum ameliorates post-gastrectomy insulin resistance by regulating the mTORC1 signaling pathway through the gut-liver axis
He, Z., Xiong, H., Cai, Y., Chen, W., Shi, M., Liu, L., Wu, K., Deng, X., Deng, X., & Chen, T. (2025) · Microbiological Research · doi:10.1016/j.micres.2025.128154 · Cited by 11
Kudzu root-derived carbon dots modulate gut microbiota and metabolites for pan-organ targeted macrophage polarization in synergistic diabetes therapy
Yi, J., Tang, Y., Chen, Y., Chen, L., Geng, D., Liu, L., Yu, J., Zou, L., Zeng, J., Lan, M., et al. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123967 · Cited by 8
Association between polymorphisms and hypermethylation of CD36 gene in obese and obese diabetic Senegalese females
Touré, M., Hichami, A., Sayed, A., Suliman, M., Samb, A., & Khan, N. A. (2022) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-022-00881-2 · Cited by 8
“It’s widely believed that the availability and use of free fatty contribute to the development of skeletal muscle insulin resistance, as well as to increased liver glucose production [6].”
Background
Tea seed saponin‑reduced extract ameliorates palmitic acid‑induced insulin resistance in HepG2 cells
Cho, S.-C., & Shaw, S. (2023) · Molecular Medicine Reports · doi:10.3892/mmr.2023.13149 · Cited by 8
“Flavonoid content (mg/g) ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ and phosphorylated (50). irS1 phosphorylation subsequently stimulates akt to perform further regulation.”
Does Resveratrol Improve Insulin Signalling in HepG2 Cells?
Norouzzadeh, M., Amiri, F., Saboor-Yaraghi, A. A., Shemirani, F., Kalikias, Y., Sharifi, L., Seyyedsalehi, M. S., & Mahmoudi, M. (2016) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2016.09.015 · Cited by 8
Neuroendocrine Control of Body Energy Homeostasis
Affinati, A. H., & Myers, M. G. (2021) · Europe PMC (PubMed Central) · Cited by 8
Insights into Insulin Resistance and Calcification in the Myocardium in Type 2 Diabetes: A Coronary Artery Analysis
Martín‐Saladich, Q., Simó, R., Aguadé‐Bruix, S., Simó‐Servat, O., Aparicio, C., Hernández, C., Ramírez, C., Pizzi, M. N., Roque, A., Ballester, M. Á. G., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043250 · Cited by 8
“However, the latter mechanism can be stimulated by the presence of such substrates promoting the differentiation of smooth muscle cells into osteogenic cells contributing to atherogenesis, among many other factors [30,33,34].”
Background
Preserving insulin secretion in Type 2 diabetes mellitus
Tibaldi, J. M. (2008) · Expert Review of Endocrinology & Metabolism · doi:10.1586/17446651.3.2.147 · Cited by 8
Aldehydes and disturbance of carbohydrate metabolism: Some consequences and possible approaches to its normalization
Dmitriev, L. F., & Дугин, С. Ф. (2007) · Archives of Physiology and Biochemistry · doi:10.1080/13813450701384783 · Cited by 8
“The majority of insulin signals are generated and modulated through phosphorylation of tyrosine, a protein–insulin receptor substrate, IRS1, its homologue IRS2, and other accessory proteins.”
Background
Chitooligosaccharide Biguanide Repairs Islet β‐Cell Dysfunction by Activating the IRS‐2/PI3K/Akt Signaling Pathway in Type 2 Diabetic Rats
Zou, Y., Wang, Y., Zhang, S., Wu, Y., & Liu, X. (2019) · Advanced Therapeutics · doi:10.1002/adtp.201800136 · Cited by 8
Adipose Tissue
Eckel, J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809518-8.00002-7 · Cited by 11
Insulin suppresses transcriptional activity of yes-associated protein in insulin target cells
Sayedyahossein, S., Hedman, A. C., & Sacks, D. B. (2019) · Molecular Biology of the Cell · doi:10.1091/mbc.e19-04-0205 · Cited by 8
“PI3K is responsible for most of the metabolic effects of insulin (White, 2003), while MAPK predominantly mediates mitogenic cellular responses (Avruch, 2007).”
Background
Characterization of Huh7 cells after the induction of insulin resistance and post-treatment with metformin
Villalva-Pérez, J. M., Ramírez‐Vargas, M. A., Serafín-Fabián, J. I., Ramı́rez, M., Moreno‐Godínez, M. E., Espinoza-Rojo, M., & Flores‐Alfaro, E. (2020) · Cytotechnology · doi:10.1007/s10616-020-00398-4 · Cited by 10
“The reduction in glucose uptake induced by insulin stimulation suggested a negative regulation in the PI3KAkt pathway activated by insulin (White 2003).”
Background
Effect of submerged culture of Ceriporia lacerata mycelium on GLUT4 protein in db/db mouse
Shin, E. J., Kim, J., Kim, J., Park, Y. M., Yoon, S. K., Jang, B., Lee, S., & Kim, B.-C. (2015) · Korean Journal of Food Preservation · doi:10.11002/kjfp.2015.22.6.893 · Cited by 8
“Akt의 인산화는 GLUT4 translocation을 증가시켜 혈 당을 조절한다(12-16).”
The New Anesthesia Diet Plan: Keeping Perioperative Carbs in Check
Coursin, D. B., & Prielipp, R. C. (2004) · Anesthesia & Analgesia · doi:10.1213/01.ane.0000130388.70236.29 · Cited by 8
“By contrast, there is an epidemic of Type 2 DM, which manifests as a spectrum of glucose dysregulation secondary to a combination of relative insulin deficiency, peripheral insulin resistance, and excessive hepatic gluconeogenesis (10, 11 ).”
Background
Chronic ethanol treatment of human hepatocytes inhibits the activation of the insulin signaling pathway by increasing cytosolic free calcium levels
Chen, Y.-M., Zhao, J., Liu, Y., Chen, J., & Jiang, R. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2282 · Cited by 7
“IR tyrosine kinase activation subsequently recruits and phosphorylates several substrates, including IRS1-4, thereby providing specific docking sites for the recruitment of other downstream signaling proteins, leading to the activation of the PI3K → PKB signaling cascades (21,22).”
The insulin receptor endocytosis
Wu, J., Park, S. H., & Choi, E. (2022) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2022.06.020 · Cited by 7
Evaluation of the suitability of 19 pharmacogenomics biomarkers for individualized metformin therapy for type 2 diabetes patients
Xhakaza, L., Abrahams-October, Z., Pearce, B., Masilela, C. M., Adeniyi, O. V., Johnson, R., Ongole, J. J., & Benjeddou, M. (2020) · Drug metabolism and drug interactions · doi:10.1515/dmpt-2020-0111 · Cited by 7
Anti-Hyperglycemic Effect of Single Administered Gardeniae Fructus in Streptozotocin-Induced Diabetic Mice by Improving Insulin Resistance and Enhancing Glucose Uptake in Skeletal Muscle
Yu, Q., Takahashi, T., Nomura, M., & Kobayashi, S. (2013) · Chinese Medicine · doi:10.4236/cm.2013.44019 · Cited by 7
“Diabetes mellitus is a group of metabolic diseases marked by hyperglycemia, which arises from abnormal insulin secretion and/or peripheral insulin resistance [2].”
Old biliverdin reductase: Links to insulin resistance and may be a novel therapeutic target
Wu, B., Liu, X., & Shen, J. (2008) · Medical Hypotheses · doi:10.1016/j.mehy.2008.02.007 · Cited by 7
Insulin Modulates the Bioenergetic and Thermogenic Capacity of Rat Brown Adipocytes In Vivo by Modulating Mitochondrial Mosaicism
Golić, I., Kalezic, A., Janković, A., Jonić, S., Korać, B., & Korać, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239204 · Cited by 8
“Mild hyperinsulinemia can be tolerated for a short time, but chronic hyperinsulinemia triggers insulin resistance and contributes to the etiology of diabetes [24].”
Background
Insulin Resistance in Obesity
Qi, Y., Guo, X., & Guo, S. (2016) · Springer eBooks · doi:10.1007/978-3-319-11251-0_28 · Cited by 7
Mechanism of Insulin Action
White, M. F. (2016) · Wiley eBooks · doi:10.1002/9781118924853.ch8 · Cited by 8
Effect of antihypertensive treatments on insulin signalling in lympho-monocytes of essential hypertensive patients: A pilot study
Ciuceis, C. D., Flati, V., Rossini, C., Rufo, A., Porteri, E., Gregorio, J. D., Petroboni, B., Boria, E. L., Donini, C., Pasini, E., et al. (2014) · Blood Pressure · doi:10.3109/08037051.2014.901021 · Cited by 6
Covalent N-arylation by the pollutant 1,2-naphthoquinone activates the EGF receptor
Nakahara, K., Hamada, K., Tsuchida, T., Takasugi, N., Abiko, Y., Shien, K., Toyooka, S., Kumagai, Y., & Uehara, T. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100524 · Cited by 6
Identification of sphingosine 1-phosphate level and MAPK/ERK signaling in pancreatic β cells
Park, J. H., Park, K. K., Choe, J. Y., & Jang, K. M. (2021) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2040266.133 · Cited by 6
CIRCULATING GHRELIN LEVELS AND SUSCEPTIBILITY TO COLORECTAL CÂNCER
Asadi, A., Farahani, H., Mahmoudi, T., Tabaeian, S. P., Rezamand, G., Mohammadbeigi, A., Dabiri, R., Nobakht, H., Rezvan, S., & MOHAMMADI, F. (2021) · Arquivos de Gastroenterologia · doi:10.1590/s0004-2803.202100000-54 · Cited by 6

Authors: White, M. F.
Affiliations: Joslin Diabetes Center (US)
Corresponding author: White, Morris F.
ORCID: White, Morris F.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2003-12-05
Volume: 302
Issue: 5651
Pages: 1710-1711
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1092952
OpenAlex: W2115177689
Cited by: 733
References: 19
Citations by year: 2026: 7 · 2025: 17 · 2024: 13 · 2023: 21 · 2022: 24 · 2021: 35 · 2020: 32 · 2019: 30 · 2018: 36 · 2017: 35 · 2016: 39 · 2015: 47 · 2014: 35 · 2013: 39 · 2012: 50
FWCI: 9.65
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: insulin signaling, insulin resistance, obesity, type 2 diabetes, pancreatic beta-cell failure, chronic inflammation, insulin receptor substrate 2
MeSH terms: Animals, Diabetes Mellitus, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Inflammation, Insulin, Insulin Resistance, Islets of Langerhans, Models, Biological, Obesity, Phosphoproteins, Phosphorylation, Receptor, Insulin, Somatomedins, Signal Transduction, Cytokines, Intracellular Signaling Peptides and Proteins, Mice, Insulin Receptor Substrate Proteins

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