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Review Open Access

Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review)

  • Authors:
    • Weikang Tang
    • Huixia Liu
    • Xuan Li
    • Siyao Deng
    • Changyu Gao
  • View Affiliations / Copyright

    Affiliations: School of Medicine, Tarim University, Alaer, Xinjiang Uyghur Autonomous Region 843300, P.R. China, Department of Prescription Science, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China
    Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 63
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    Published online on: December 9, 2025
       https://doi.org/10.3892/mmr.2025.13773
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Abstract

Diabetes is a metabolic disorder that has notable impacts on human health. Since improving insulin sensitivity and metabolic homeostasis is important for the treatment of diabetes and its complications, there is a need to evaluate therapies that improve insulin resistance. The aim of the present review was to introduce the effects of the insulin receptor substrate (IRS)/PI3K/Akt pathway on insulin resistance by summarizing and evaluating all existing insulin signaling pathway studies as the entry point, and to integrate the processes and mechanisms through which drugs alleviate insulin resistance. Peer‑reviewed studies and reports on diabetes, insulin resistance and drug therapy were retrieved by searching websites such as PubMed (https://pubmed.ncbi.nlm.nih.gov/) and China National Knowledge Infrastructure (CNKI, https://www.cnki.net/), as well as by a manual search. The present review discusses the association between diabetes and the IRS/PI3K/Akt pathway, the treatment of diabetes by regulating this pathway to alleviate insulin resistance, the process and mechanism of combining drugs to alleviate insulin resistance, including natural compounds, Traditional Chinese Medicine and active ingredients, and the latest modern treatment methods. In conclusion, the present review summarizes the potential role of the IRS/PI3K/Akt pathway in the treatment of diabetes through its effect on insulin resistance and elucidates the therapeutic effects of drugs targeting this pathway.
View Figures

Figure 1

Flow chart of the mechanism of the
IRS/PI3K/Akt signaling pathway in diabetes-induced insulin
resistance. IRS, insulin receptor substrate; GLUT4, glucose
transporter type 4; GSK3, glycogen synthase kinase 3; PIP2,
phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol
3,4,5-triphosphate; P, phosphate group.

Figure 2

Effects of the IRS/PI3K/Akt pathway
on hepatic insulin resistance. The mechanism of the IRS/PI3K/Akt
pathway in insulin resistance and the therapeutic effect of drugs
was explored in the pathogenesis of diabetes. IRS, insulin receptor
substrate; GSK3β, glycogen synthase kinase 3β; P, phosphate
group.
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Spandidos Publications style
Tang W, Liu H, Li X, Deng S and Gao C: Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review). Mol Med Rep 33: 63, 2026.
APA
Tang, W., Liu, H., Li, X., Deng, S., & Gao, C. (2026). Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review). Molecular Medicine Reports, 33, 63. https://doi.org/10.3892/mmr.2025.13773
MLA
Tang, W., Liu, H., Li, X., Deng, S., Gao, C."Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review)". Molecular Medicine Reports 33.2 (2026): 63.
Chicago
Tang, W., Liu, H., Li, X., Deng, S., Gao, C."Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review)". Molecular Medicine Reports 33, no. 2 (2026): 63. https://doi.org/10.3892/mmr.2025.13773
Copy and paste a formatted citation
x
Spandidos Publications style
Tang W, Liu H, Li X, Deng S and Gao C: Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review). Mol Med Rep 33: 63, 2026.
APA
Tang, W., Liu, H., Li, X., Deng, S., & Gao, C. (2026). Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review). Molecular Medicine Reports, 33, 63. https://doi.org/10.3892/mmr.2025.13773
MLA
Tang, W., Liu, H., Li, X., Deng, S., Gao, C."Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review)". Molecular Medicine Reports 33.2 (2026): 63.
Chicago
Tang, W., Liu, H., Li, X., Deng, S., Gao, C."Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review)". Molecular Medicine Reports 33, no. 2 (2026): 63. https://doi.org/10.3892/mmr.2025.13773
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