Cited by 1,673Metabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancerAdipokines, Inflammation, and Metabolic Diseases

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The PI3K/AKT pathway in obesity and type 2 diabetes

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Huang, Xingjun, Liu, Guihua, Guo, Jiao, Su, Zhengquan·2018·International Journal of Biological Sciences

DOI 10.7150/ijbs.27173PMC PMC6158718

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Abstract

Obesity and type 2 diabetes mellitus are complicated metabolic diseases that affect multiple organs and are characterized by hyperglycaemia. Currently, stable and effective treatments for obesity and type 2 diabetes mellitus are not available. Therefore, the mechanisms leading to obesity and diabetes and more effective ways to treat obesity and diabetes should be identified. Based on accumulated evidences, the PI3K/AKT signalling pathway is required for normal metabolism due to its characteristics, and its imbalance leads to the development of obesity and type 2 diabetes mellitus. This review focuses on the role of PI3K/AKT signalling in the skeletal muscle, adipose tissue, liver, brain and pancreas, and discusses how this signalling pathway affects the development of the aforementioned diseases. We also summarize evidences for recently identified therapeutic targets of the PI3K/AKT pathway as treatments for obesity and type 2 diabetes mellitus. PI3K/AKT pathway damaged in various tissues of the body leads to obesity and type 2 diabetes as the result of insulin resistance, and in turn, insulin resistance exacerbates the PI3K/AKT pathway, forming a vicious circle.

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Background
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Self-citation
Chitosan oligosaccharide activates brown adipose tissue by modulating the gut microbiota and bile acid pathways based on faecal microbiota transplantation
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Self-citation
Daidzein improved glucose homeostasis via PI3K/AKT and modulated the communities of gut microbiota in turbot (Scophthalmus maximus L.)
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“PI3K‐Akt signaling pathway The synthesis of free fatty acids (FFAs) in organs Inhibition NAFLD ↓ ‐In obese subjects, over‐circulating of FFAs driven by PI3K‐Akt signaling pathway can influence on negative side effects to organs, resulting in imbalance of glucose and lipid metabolism [71]”
Background
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“37,38 In addition, it is noteworthy that PI3K–AKT pathway along with the Fc-gamma receptors-mediated pathway identified in hypomethylated gene sets.”
Background
Characterization and evaluation of the in vitro and in vivo anti-diabetic activities of camel milk protein hydrolysates derived with different protease digestions
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Highlighting the effects of high-intensity interval training on the changes associated with hypertrophy, apoptosis, and histological proteins of the heart of old rats with type 2 diabetes
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Melatonin increases AKT and SOD gene and protein expressions in diabetic rats
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“Overall, the PI3K/AKT signaling pathway plays a crucial role in the regulation of glucose and lipid metabolism in the liver, and abnormalities in this pathway can contribute to the development of DM and other metabolic disorders [17].”
Background
Follicular fluid exosomes inhibit expression of BTG2 and promote glucose uptake in granulosa cells by delivering miR-21-5p
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Whole Grain Proso Millet (Panicum miliaceum L.) Attenuates Hyperglycemia in Type 2 Diabetic Mice: Involvement of miRNA Profile.
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“The PI3K/ AKT signaling pathway is an important pathway of insulin signaling, involved in glucose and lipid metabolism along with cell proliferation and survival (Huang et al., 2018).”
Background
A Botanical Mixture Consisting of Inula japonica and Potentilla chinensis Relieves Obesity via the AMPK Signaling Pathway in 3T3-L1 Adipocytes and HFD-Fed Obese Mice
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Background
Research progress on the role of FGF21 in insulin resistance
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“Meanwhile, central insulin resistance is thought to underlie cardiometabolic diseases due to the important role of insulin in brain circuits that control food intake and voluntary activity (8, 9).”
A network toxicology and molecular docking-based approach revealed shared hepatotoxic mechanisms and targets between the herbicide 2,4-D and its metabolite 2,4-DCP.
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“…receptor substrate (IRS) level, where serine phosphorylation of IRS proteins impairs their functionality, preventing the activation of downstream signaling molecules, such as phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) (Huang et al. 2018; Ramasubbu and Devi Rajeswari 2023).”
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“The observations showed that the introduction of green tea extract showed a signiﬁcant decrease in total cholesterol levels and plasma LDL concentrations (Bogdanski et al. 2012; Huang et al. 2018a, b).”
RNA-binding protein GIGYF2 orchestrates hepatic insulin resistance through STAU1/PTEN-mediated disruption of the PI3K/AKT signaling cascade
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“Conversely, IR further impairs the PI3K/AKT pathway, creating a feedback loop that exacerbates both conditions (Huang et al. 2018).”
Background
Ebselen improves lipid metabolism by activating PI3K/Akt and inhibiting TLR4/JNK signaling pathway to alleviate nonalcoholic fatty liver.
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Photobiomodulation (PBM): a therapeutic technique targeting fibroblast cell regeneration and survival in diabetic wounds
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Protective Effects of Different Selenium Green Tea Polysaccharides on the Development of Type 2 Diabetes in Mice
Gao, W.-L., Zheng, Z., Wang, X.-H., Wang, L., Zhang, N., Liu, H., Cong, X., Li, S.-Y., & Zhu, Z.-Z. (2023) · Foods · doi:10.3390/foods12234190 · Cited by 12
“GLUT-2 and GSK-3 β , which play crucial roles in glucose transport, absorption, and glycogen synthase activity, are regarded as downstream molecules within the PI3K-Akt signaling pathway [26].”
Background
Network pharmacology-based screening of the active ingredients and mechanisms of Cymbaria daurica against diabetes mellitus
Shi, R., Chen, D.-X., Ji, M.-Y., Zhou, B.-C., Zhang, Z.-Y., Zhang, C., & Li, M.-H. (2023) · Food Science and Human Wellness · doi:10.1016/j.fshw.2023.03.022 · Cited by 12
A review: Mechanism and prospect of gastrodin in prevention and treatment of T2DM and COVID-19
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“Specifically, we urgently need to explore the effects of gastrodin on GLUT4/GSK3 β /GS/FOXO1 through PI3K/AKT pathway, as well as the changes of glucose uptake, glycogen synthesis and blood glucose levels in the context of diabetes.”
BackgroundInfluential
PLAAT1 deficiency alleviates high‐fat diet‐induced hepatic lipid accumulation in mice
Rahman, S., Sasaki, S., Uyama, T., Hussain, Z., Sikder, M. M., Saiga, H., Ohmura‐Hoshino, M., Ohta, K., Miki, Y., Hoshino, K., et al. (2023) · The FASEB Journal · doi:10.1096/fj.202201033r · Cited by 15
Association of physical activity with increased PI3K and Akt mRNA levels in adipose tissues of obese and non-obese adults
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Uses of Papaya Leaf and Seaweed Supplementations for Controlling Glucose Homeostasis in Diabetes
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microRNA-96 targets the INS/AKT/GLUT4 signaling axis: Association with and effect on diabetic retinopathy
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Authors: Huang, X., Liu, G., Guo, J., & Su, Z.
Affiliations: Guangdong Pharmaceutical University (CN)
Shenzhen Center for Disease Control and Prevention (CN)
Corresponding author: Guo, Jiao
Su, Zhengquan
ORCID: Liu, Guihua
Guo, Jiao
Su, Zhengquan
Venue: International Journal of Biological Sciences
Publisher: Ivyspring International Publisher
Published: 2018
Volume: 14
Issue: 11
Pages: 1483-1496
ISSN: 1449-2288 (ISSN-L)
DOI: 10.7150/ijbs.27173
PMC: PMC6158718
OpenAlex: W2886504687
Cited by: 1,673
References: 171
Citations by year: 2026: 197 · 2025: 296 · 2024: 282 · 2023: 258 · 2022: 246 · 2021: 211 · 2020: 136 · 2019: 44 · 2018: 3
FWCI: 9.71
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
Locations: International Journal of Biological Sciences (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (2017-02, 81173107)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: PI3K/Akt signaling, obesity, type 2 diabetes, insulin resistance, hyperglycemia, skeletal muscle, adipose tissue, liver, pancreas, therapeutic target, metabolic disorders
MeSH terms: Animals, Diabetes Mellitus, Type 2, Humans, Insulin Resistance, Obesity, Signal Transduction, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt

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The PI3K/AKT pathway in obesity and type 2 diabetes

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