The DOI matches its Crossref record; 167 of the 171 references it cites were found in a registry or an index.
The PI3K/AKT pathway in obesity and type 2 diabetes
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“AKT activation leads to increased glucose transporter 4 (GLUT4) expression and translocation, ultimately leading to increased glucose uptake.”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [48]
The cited source says what the claim attributes to it.
In the citing paper
“PI3K is an enzyme that activates protein kinase B (AKT), which regulates glucose metabolism, among other intracellular functions [48].”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [48]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509 · cited 1×
“AKT-mediated mTORC1 activation regulates a number of downstream effectors proteins through phosphorylation, including the well-characterized effectors p70 ribosomal S6 protein kinase-1 (S6K1) and eukaryotic translation initiation factor-4E (eIF4E)binding protein-1 (4E-BP1), to increase protein synthesis [43, 44].”
BackgroundPhosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216 · cited 1×
“First, phosphorylation of the threonine 308 (AKT1) in the kinase domain by phosphoinositide-dependent protein kinase 1 (PDK1) initiates the activation process [19], subsequent phosphorylation at serine 473 (AKT1) in the carboxy-terminal regulatory domain through mTOR complex 2 (mTORC2)[17, 20], which is activated by a…”
BackgroundAKT/PKB signaling: navigating downstream
Manning, B. D., & Cantley, L. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.009 · Cited by 6,115 · cited 1×
“AKT regulates two processes by glycolysis Glucose 6-phosphate and glycogen synthase kinase 3 (GSK3) to produce cellular energy via glycolysis and promotes glycogen production by inhibiting [30].”
BackgroundMechanisms linking obesity to insulin resistance and type 2 diabetes
Kahn, S. E., Hull, R. L., & Utzschneider, K. M. (2006) · Nature · doi:10.1038/nature05482 · Cited by 5,448 · cited 1×
“In obese subjects, excess levels of circulating FFAs, which are caused by a blunted response of adipose tissues, impairs the function of β cells [150].”
BackgroundInhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244 · cited 8×
“In the feeding state, SREBP-1c is regulated by four pathways: activated AKT stimulates liver X receptor (LXR), which is require for SREBP-1c transcription [64]; activated AKT stimulates mTORC1 to activate SREBP-1c transcription, and mTORC1 also inhibits Lipin-1, which decreases the half-life of nuclear SREBP-1c [65, 6…”
BackgroundInfluentialAKT/PKB Signaling: Navigating the Network
Manning, B. D., & Toker, A. (2017) · Cell · doi:10.1016/j.cell.2017.04.001 · Cited by 3,772 · cited 2×
“Similar phosphorylation events are observed at corresponding residues in AKT2 (T309 and S474) and AKT3 (T305 and S472) [22].”
BackgroundRole of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117 · cited 1×
“In the presence of persistent excess energy availability, leptin signalling activates other pathways, such as STAT3 or SH2-containing tyrosine phosphatase, to predominantly regulate food intake in POMC neurons [90, 113, 119].”
BackgroundAlessi, D. R., James, S. R., Downes, C. P., Holmes, A. B., Gaffney, P. R. J., Reese, C. B., & Cohen, P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00122-9 · Cited by 2,874 · cited 1×
“First, phosphorylation of the threonine 308 (AKT1) in the kinase domain by phosphoinositide-dependent protein kinase 1 (PDK1) initiates the activation process [19], subsequent phosphorylation at serine 473 (AKT1) in the carboxy-terminal regulatory domain through mTOR complex 2 (mTORC2)[17, 20], which is activated by a…”
BackgroundEndoplasmic reticulum stress and the inflammatory basis of metabolic disease
Hotamisligil, G. S. (2010) · Cell · doi:10.1016/j.cell.2010.02.034 · Cited by 2,802 · cited 1×
“Chronic metabolic inflammation and endoplasmic reticulum (ER) stress also impair hepatic insulin-AKT signalling and subsequently causes insulin resistance [106, 107].”
BackgroundHealth and economic burden of the projected obesity trends in the USA and the UK
Wang, Y. C., McPherson, K., Marsh, T., Gortmaker, S. L., & Brown, M. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60814-3 · Cited by 2,775 · cited 1×
“The prevalence of obesity has grown at an alarming rate although specific public health policies and treatment efforts have been developed to resist the obesity epidemic [1], potentially leading to increased numbers of patients affected by complications of obesity, such as the most devastating type 2 diabetes mellitus…”
Background
Flagged first, then by citations
4 of the 171 references couldn’t be matched to a known paper.
Research works printed but not linked: 5
- [98]Yecies Jessica L Zhang Hui H Menon S Liu S Yecies D Lipovsky Alex I Akt Stimulates Hepatic SREBP1c and Lipogenesis through Parallel mTORC1-Dependent and Independent Pathways Cell metabolism 2011 14 1 21 32 21723501 PMC3652544
- [120]Al-Qassab H Smith MA Irvine EE Guillermet-Guibert J Claret M Choudhury AI Dominant role of the p110beta isoform of PI3K over p110alpha in energy homeostasis regulation by POMC and AgRP neurons Cell metabolism 2009 10 5 343 54 19883613 PMC2806524
- [144]Bernal-Mizrachi E Wen W Stahlhut S Welling CM Permutt MA Islet beta cell expression of constitutively active Akt1/PKB alpha induces striking hypertrophy, hyperplasia, and hyperinsulinemia J Clin Invest 2001 108 11 1631 8 11733558 PMC200992
- [147]Wang HW Mizuta M Saitoh Y Noma K Ueno H Nakazato M Glucagon-like peptide-1 and candesartan additively improve glucolipotoxicity in pancreatic beta-cells Metabolism 2011 60 8 1081 9 21255808
- [161]Villani V Milanesi A Sedrakyan S Da Sacco S Angelow S Conconi MT Amniotic fluid stem cells prevent beta-cell injury Cytotherapy 2014 16 1 41 55 24210784 PMC4374982
Cited by
Sorted by citations
Items 801–900 of 1,008
Wang, M., Qu, Y., Wang, S., & Qu, Z. (2024) · Open Medicine · doi:10.1515/med-2024-1095 · Cited by 1
“In recent years, studies have found that PI3K/Akt/GSK-3 β is a key insulin signaling pathway mainly regulated by upstream factors like IGF-1 and external stimuli [26,27].”
Lee, C.-C., Kono, T., Syed, F., Weaver, S. A., Sohn, P., Wu, W., Chang, G., Liu, J., Rupnik, M. S., & Evans-Molina, C. (2023) · bioRxiv · doi:10.1101/2023.12.06.570443 · Cited by 1
“To test whether NaB has beneficial effects on insulin secretion in humans, islets isolated from human cadaveric donors with T2D were incubated in the absence or presence of NaB for 24 hours prior to a GSIS assay.”
BackgroundMethodInfluentialLiu, M., Wang, X., Yang, J.-S., & Qin, D. (2023) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-023-04248-6 · Cited by 1
“Impaired PI3K/ AKT-mediated glucose transport and glycogen synthesis are significant contributors to the pathogenesis of type 2 diabetes mellitus and obesity [40].”
BackgroundAn expanded clinical spectrum of hypoinsulinaemic hypoketotic hypoglycaemia
Welters, A., Leiter, S. M., Bachmann, N., Bergmann, C., Hoermann, H., Korsch, E., Meißner, T., Payne, F., Williams, R. M., Hussain, K., et al. (2023) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-023-02954-5 · Cited by 1
“Recently, this has additionally been attributed in some children to genetic activation of the phosphoinositide 3-kinase (PI3K)–AKT-mTOR signalling cascade, a crucial component of intracellular insulin signalling [2–5].”
BackgroundDevelopment and validation of a model for predicting the risk of prostate cancer
Li, Y.-D., Ren, Z., Gou, Y., Wei-Tan, Liu, C., & Gao, L. (2023) · International Urology and Nephrology · doi:10.1007/s11255-023-03837-1 · Cited by 1
“The phosphatase and tensin homologue (PTEN)–PI3K/AKT signaling pathway had been proved to be involved in the occurrence of PCa and diabetes [15, 16].”
Erukainure, O., Oyebode, O., Chuturgoon, A., Ghazi, T., Muhammad, A., Aljoundi, A., Elamin, G., Chukwuma, C. I., & Islam, M. S. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.117249 · Cited by 1
Marzan, A. A., Shahi, S., Arman, M. S., Hasan, M. Z., & Ghosh, A. (2023) · Advances in Biomarker Sciences and Technology · doi:10.1016/j.abst.2023.10.001 · Cited by 1
Heidari, M., Hajizadeh-Sharafabad, F., & Alizadeh, M. (2022) · Nutrition clinique et metabolisme · doi:10.1016/j.nupar.2022.09.004 · Cited by 1
Lima, A. O., Malheiros, J., Afonso, J., Petrini, J., Coutinho, L., Diniz, W. J. D. S., Bressani, F. A., Tizioto, P., de Oliveira, P. N. D., Ribeiro, J., et al. (2022) · Mammalian Genome · doi:10.1007/s00335-022-09960-1 · Cited by 1
“The AKT is an integral part of the PI3K/AKT pathway, in which members of the PI3K family activate AKT (Huang et al. 2018).”
BackgroundXiang, Z., Deng, J., Yu, M., & Xia, C. (2026) · Journal of Functional Foods · doi:10.1016/j.jff.2026.107517
Kou, Z., Han, J., Xue, Y., Fu, Y., Yi, Z., & Li, M. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.117598
Apparow, S., Zakaria, M. A., Zamri, M. Z. H., Izazi, S. M. M., Varma, L., Abdullah, N., Habib, A., & Abdullah‐Zawawi, M. (2026) · Biomedicines · doi:10.3390/biomedicines14112453
Brain insulin resistance and microglial immunometabolic dysregulation in neurodegenerative diseases
Liu, X., Zhang, X., Su, Y., Guan, G., Luo, X., & Zhang, P. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.2002283
“The PI3K and Akt pathway is one of the major signaling cascades in brain insulin signaling and participates in the regulation of glucose uptake, cell survival, synaptic plasticity, protein synthesis, and anti-inflammatory responses (Huang et al., 2018).”
Yu, G.-S., Zhou, D.-H., Wang, Z.-H., Fu, X.-H., Chen, N.-N., Tian, S., Ma, Y.-G., Zou, H., Song, R.-L., Bian, J.-C., et al. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.154999
Li, Z.-W., Huang, C.-R., Chen, Y.-Q., Xie, X.-Y., Liao, Y.-Y., Chen, L.-P., Dong, G.-T., Xie, J.-H., Li, Y.-C., Chen, J.-N., et al. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179449
Self-citationMiro1 mediates skeletal muscle insulin resistance in type 2 diabetes
Heintz, E. C., Dantas, W. S., Taylor, A. L., Zunica, E. R. M., Belmont, K. P., Slone, J. M., Mey, J. T., Beyl, R. A., Vandanmagsar, B., Parry, H. A., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-77278-6
“Miro1 SkM − / − mice had increased AKT and AS160 signaling in skeletal muscle compared to Miro1 fl / fl mice (Fig.”
InfluentialAmjad, L., Kaushalya, K. G. D., & Rupasinghe, H. P. V. (2026) · Food & Function · doi:10.1039/d6fo02463g
Sodium Butyrate Attenuates Doxorubicin Sardiotoxicity Through GPR41/GPR43–Sox4–PI3K/Akt Signaling
Liu, H., Sun, L., Zhang, J., Jia, T., Xu, H., 刘佳妮, Wang, J., Ma, H., & Ma, J. (2026) · Cardiovascular Toxicology · doi:10.1007/s12012-026-10208-6
“PI3K/Akt is a central pro-survival pathway that regulates metabolism and apoptosis [18–20], and Sox4 can modulate PI3K/Akt signaling in several biological settings [21, 22].”
Wang, H.-Y., Sun, L.-T., Mao, H.-D., Mei, Y., Ni, J.-P., & Wang, L.-R. (2026) · Adipocyte · doi:10.1080/21623945.2026.2743441
“As a significant regulator of glucose, lipid, and protein metabolism, the PI3K/AKT pathway is integral to the process of obesity [23,24] and mediates the proliferation, differentiation, and apoptosis of 3T3-L1 cells [21,43–45].”
Syringin inhibits insulin resistance through the PI3K/AKT pathway
Wang, H., Han, J., Yun, L., & Wang, X. (2026) · Acta Pharmaceutica · doi:10.2478/acph-2026-0024
“Interleukin-6 (IL-6) is a cytokine with pleiotropic effects, playing a vital role in inflammatory responses and metabolic regulation (17).”
Association of waist circumference trajectories with incident chronic kidney disease.
Lee, J.-H., Hwang, H.-S., Park, J., Kim, Y.-M., Kim, D.-H., & Park, H.-K. (2026) · Kidney Research and Clinical Practice · doi:10.23876/j.krcp.26.129
Ai, K.-Y., Wei, M.-L., Zhang, N.-H., Chen, S.-W., Hong, H.-L., Gong, Y., Huang, X.-X., & Li, S.-L. (2026) · Marine Life Science & Technology · doi:10.1007/s42995-026-00420-2
Self-citationDong, Q., Xu, W., Li, R., Abbas, M., Guo, Q., Ma, L., Zhang, C., Ban, Y., Zhang, W., Yang, X., et al. (2026) · Journal of Functional Foods · doi:10.1016/j.jff.2026.107463
Ginsenosides as Regulators of Energy Metabolism: Benefits and Mechanisms
Wan, S., Zou, Q., Yuting, H., Zhang, K., Li, N., & Zhang, K. (2026) · Journal of Nutrition · doi:10.1016/j.tjnut.2026.101859
Verma, A., Majumdar, A., Alam, O., & Sharma, M. (2026) · Archiv der Pharmazie · doi:10.1002/ardp.70361
“Activation of PI3K triggers a cascade involving Akt phosphorylation, thereby facilitating GLUT‐4 translocation to the plasma membrane [27].”
Tolentino, A. M., Xu, Y., Hsu, M.-F., Haj, F. G., & Vahmani, P. (2026) · Journal of Nutrition · doi:10.1016/j.tjnut.2026.101889
Kuddus, A., Islam, M. E., Parvin, M. S., Dutta, S., & Ahmed, M. F. R. S. (2026) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2026.109454
Sun, C., Zhu, K., Li, Y., Li, F., Zhang, Y., Wang, Z., Zhao, H., Wang, W., Zhang, X.-L., Zhang, W., et al. (2026) · Foods · doi:10.3390/foods15193378
Duan, Z., Peng, J., Zhu, H., Ruan, B., & Cao, M. (2026) · Cytotechnology · doi:10.1007/s10616-026-01071-y
“The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is critical for the development of IR (Huang et al. 2018).”
Mohiuddin, M. (2026) · Health Science Reports · doi:10.1002/hsr2.73275
“These toxicities arise because the PI3K/Akt pathway also plays critical physiological roles in insulin signaling, glucose homeostasis, and normal cellular metabolism [5, 83, 84].”
Insulin-like growth factor receptor signaling in physiology and disease
Dilawar, M., Malik, A., Liao, J., Shen, P., Huang, Z., Zhang, P., Wang, J., Zhang, N., Nisar, M. F., & Chen, G. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02843-w · Cited by 1
“111 Through these mechanisms, the PI3K – AKT pathway coordinately regulates glucose, lipid and protein metabolism 112 while also modulating gene expression programs that govern cell proliferation, growth, differentiation and apoptosis 113 (Fig.”
Role of Protein Kinase C in Insulin Resistance and Metabolic Syndrome
Cruz-Villarreal, D. E., Hernández-González, K. D., & Olivares-Reyes, J. A. (2026) · Kinases and Phosphatases · doi:10.3390/kinasesphosphatases4030025
“…tyrosine phosphatase 1B (PTP1B) [7], which contributes to the dephosphorylation of the receptor and IRS; a decrease in the activity of phosphatidylinositol 3-kinase (PI3K) and Akt [8]; and defects in the expression and function of the insulin-dependent glucose transporter type 4 (GLUT4) [9].”
Circular RNAs at the crossroads of oxidative stress: novel targets for precision therapeutics
Singh, V., Sinha, R., Das, J., Islam, A., Sridhar, S. B., Panigrahy, U. P., Mantry, S., Shahin, H., Adhikary, K., Pal, R., et al. (2026) · Genome Instability & Disease · doi:10.1007/s42764-026-00190-2
“Numer - ous circRNAs have been shown to regulate the oxidative stress response. circFOXO3 sequesters antioxidant proteins and influences cell viability under oxidative stress (Pizzino et al., 2017, Huang et al., 2018). circZNF609 and circRNA-SORE are elevated in cancer and enhance resistance to ROS.”
Xu, D.-Y., Liu, R.-D., Zhang, Z.-Q., Zhang, X.-W., Gao, G., & Xie, Z.-S. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.122373
Wang, M., Liu, Q.-L., Han, D., Li, J.-B., Wang, X., Ma, W., & Wang, C.-Q. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1897620
“Previous studies have identified insulin as the primary ligand for the PI3K/AKT pathway, which regulates lipid and glucose metabolism in essential organs, including the brain, liver, muscle, adipose tissue, and pancreas (Huang et al., 2018).”
Singh, R., Paliwal, T., Joshi, R., Paliwal, V., Dubey, P., Bhardwaj, S., Jain, S., Paliwal, S., & Sharma, S. K. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.154524
Yu, X., Xiang, S., Jia, T., Zhang, Z., Sun, Y., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Brühl, R., Garavan, H., et al. (2026) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2026.100820
Mechanisms of traditional Chinese medicine in treatment of polycystic ovary syndrome: A review
塗士彥, 武露明, Cheng, T., Tao, J., Fan, X., Wang, Y., & Wang, Y. (2026) · Chinese Herbal Medicines · doi:10.1016/j.chmed.2026.09.001
Nanotherapeutic Strategies for MASLD: From Pathological Mechanisms to Targeted Delivery Systems
Li, N., Zhou, D., Ye, F., Yu, F., Hao, L., Li, S., Peng, Q., Deng, J., & Hu, X. (2026) · International Journal of Nanomedicine · doi:10.2147/ijn.s631025
“147 However, under conditions of obesity, lipotoxicity, and chronic low-grade inflammation, free fatty acids, ceramides, diacylglycerols, and inflammatory cytokines interfere with insulin signaling transduction pathways such as IRS-1/AKT, resulting in reduced hepatocellular responsiveness to…”
Othman, N., Aminuddin, A., Hamid, A. A., Abidin, S. Z., Syafruddin, S. E., Ahmad, M. F., Jaffar, F., Basri, N. A. O., & Ugusman, A. (2026) · Biomedicines · doi:10.3390/biomedicines14092038
“Dysregulation of this pathway has been implicated in endothelial dysfunction and vascular complications associated with diabetes [29].”
Raut, S., Gawande, S., lanjekar, R., & Mahabhudhe, J. (2026) · In Silico Research in Biomedicine · doi:10.1016/j.insi.2026.100625
Adhikary, K., Godwin, T. S., Karunanithi, A., Sarkar, R., Abubakar, M., Nag, S., Barman, S., Datta, N., & Maiti, R. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18091191
Liu, W., Li, X., Liu, C., Duan, S., Zhang, X., Li, X., & Li, X. (2026) · Aquaculture · doi:10.1016/j.aquaculture.2026.744572
Sowmya, G. S., Shanmugam, Y., Arumugam, V., & Ramasamy, J. (2026) · Pharmacological Research - Modern Chinese Medicine · doi:10.1016/j.prmcm.2026.100882
Balam, F. H., Zolfaghari, F., Teymoori, F., Mousavi, M. A., Asghari, G., Yuzbashian, E., Khalaj, A., Hedayati, M., Zarkesh, M., & Saidpour, A. (2026) · Scientific Reports · doi:10.1038/s41598-026-62587-z
“Based on previous studies, our observations are consistent with prior evidence suggesting that reduced gene expression may reflect decreased systemic insulin demand rather than pathway inhibition 25,33 .”
Joseph, B. B., Sekhar, P. S., Gopalakrishnan, A. P., Mahin, A., & Raju, R. (2026) · OMICS A Journal of Integrative Biology · doi:10.1177/15578100261483317
“In contrast, insulin signaling stimulates glucose utilization, lipid synthesis, and cellular growth through activation of the PI3K – AKT – mTOR axis, whereas chronic dysregulation of this pathway contributes to insulin resistance (Huang et al., 2018).”
Jiang, Q., Teng, Y.-T., Xu, W.-J., Osada, M., Gao, X.-J., Zhang, Y., Pan, X.-Y., & Zhang, X.-J. (2026) · Journal of Experimental Zoology Part A Ecological and Integrative Physiology · doi:10.1002/jez.70127
Deng, X., Zheng, J., & Xiao, C. (2026) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.71005
Chen, L., Liu, J., Jin, X.-W., Yuan, Y.-J., Sun, Y.-M., & Wang, X. (2026) · Frontiers in Veterinary Science · doi:10.3389/fvets.2026.1912137
“In conditions of obesity and T2DM, glucose transport and glycogen synthesis are hindered due to an unstable PI3K/AKT signaling pathway (20).”
Zhang, T., Gao, L.-Y., Ren, W.-S., Guo, L., Liu, J.-B., & Xu, M.-L. (2026) · Food Reviews International · doi:10.1080/87559129.2026.2719723
Lei, W., Tripathi, A., & Hu, S. (2026) · Iranian journal of pharmaceutical research · doi:10.5812/ijpr-171105
Zhong, D.-H., Jiang, Z.-H., & Ren, T.-T. (2026) · Scientific Reports · doi:10.1038/s41598-026-65879-6
“Key KEGG terms identified in the DEG set included PI3K-Akt signaling, p53 signaling, insulin resistance, and MAPK signaling, all of which are highly relevant to insulin sensitivity, cellular stress responses, survival signaling, and diabetic complications 17,35,36 .”
Inflammatory networks between adipose tissue, liver and pancreatic islets in type 2 diabetes
Farrim, M. I. D. J. D., Silva, D., Gomes, A., Filippis, L. D., Fousteri, G., Aramini, A., Allegretti, M., Milenković, D., Menezes, R., & Dutra, R. C. (2026) · Human Genomics · doi:10.1186/s40246-026-01016-8
“…glucose uptake via GLUT4 translocation, glycogen synthesis through GSK3 inhibition, and suppression of gluconeogenesis via FOXO1 phosphorylation), the PI3K-Akt cascade functions as a broader metabolic regulator that integrates nutrient status, growth factor signaling, and inflammatory cues [37].”
Li, W., Zhang, Y., Zhang, C., Jiang, Y., Xu, Y., Yang, H., Niu, J., Lu, Z., Liu, X., 李树德, et al. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.158681
The Role of Anti-Inflammatory Nutrition in Metabolic Syndrome and Cardiometabolic Diseases
Cătană, C.-S., Marta, M. M., Popa, D., & Dronca, E. (2026) · Nutrients · doi:10.3390/nu18162732
“[21,78] Acute-phase proteins hsCRP, fibrinogen, serum Amyloid A persistently elevated. hsCRP and acute-phase proteins at minimal, physiological levels.”
Identification of Candidate miRNAs Associated with Shear Force and Intramuscular Fat in Pig Breeds
Zhang, Q., Zhang, J., Zhang, Y., Xu, J., Kumar, S., Zhao, Y., & Zhang, S.-M. (2026) · Foods · doi:10.3390/foods15152693
“In adipose tissue, this pathway promotes preadipocyte differentiation and lipid accumulation [57].”
Renal Denervation Modulates Hypothalamic Neuroinflammation via P2X7R/PI3K/Akt
Liang, W., Liu, Q. Q., Wang, Q., Wang, W., Zhang, W., Yu, H., Zhang, F., Zhao, X., Sun, R., & Yu, J. (2026) · Hypertension · doi:10.1161/hypertensionaha.126.26793
Fu, Y., Zeng, X., Zhou, B., Wang, J.-Y., & Qin, H. (2026) · Nutrients · doi:10.3390/nu18152431
Abdullah‐Zawawi, M., Apparow, S., & Jalal, M. I. A. (2026) · Egyptian Journal of Medical Human Genetics · doi:10.1186/s43042-026-00894-w
“Insulin resistance, driven by defective PI3K-Akt signaling, not only reduces glucose uptake but also promotes endothelial dysfunction and vasoconstriction, thereby contributing to hypertension [22].”
Liu, T., Tang, Z., Aierken, Z., Zhang, J., & Lei, C. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1805548
“Previous research reports have indicated that the PI3K/AKT signaling pathway plays a crucial role in regulating various metabolic processes, including gluconeogenesis, insulin secretion, and lipid metabolism, with its dysregulation being associated with insulin resistance in T2DM (39, 40).”
Genetic Determinants of Cellular Homeostasis Contributing to the Risk of Type 2 Diabetes
Timasheva, Y., Kochetova, O., Nasibullin, T., Kochetova, T. M., Balkhiyarova, Z., Korytina, G., & Nouwen, A. (2026) · Acta Naturae · doi:10.32607/actanaturae.27855
“FOXO1 also controls appetite: its hypothalamic over-expression promotes hyperphagia under cerebral insulin resistance [4].”
Arekemase, S. O., Abdulwaliyu, I., Mustapha, R. A., Hassan, U., Olusina, O. S., Udom, I. E., Sunday, A. A., & Bala, S. (2026) · Journal of Mind and Medical Sciences · doi:10.3390/jmms13030016
“This upregulation of these proteins is crucial for insulin sensitivity [129].”
Chen, G., Chen, Y., Chu, C., & Zhu, X. (2026) · Scientific Reports · doi:10.1038/s41598-026-61988-4
Chen, F. Z., Zhu, Y., Chen, J., & Chen, J. (2026) · Food Reviews International · doi:10.1080/87559129.2026.2695263
Zheng, S., Du, L., & Lv, C. (2026) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2026.2696913
Orosomucoid Enhances Insulin Sensitivity via the C–C Chemokine Receptor Type 5/Protein Kinase B Axis
Wang, P., Sun, Y., & Liu, X. (2026) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-2958-3521
Párraga-Viúdez, M. J., Sánchez-Gutiérrez, M., Quirós-Jiménez, A., Rangel-Zúñiga, O. A., López‐Miranda, J., Alcala-Diaz, J. F., & Delgado‐Lista, J. (2026) · Journal of Advanced Research · doi:10.1016/j.jare.2026.07.024
Yang, D., Yang, Z., Xiao, T.-L., He, W., Liu, L., Zhang, J., Zou, H., He, T., & Zhao, J.-H. (2026) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2026.154255
Carrasco, M., Driouech, L., Guzman, L., Barroso, E., Verdaguer, E., Auladell, C., Vázquez‐Carrera, M., Cano, A., Manzine, P. R., Ettcheto, M., et al. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118234
Metabolic and Signaling Dysregulation in a Cellular Model of Hepatic Insulin Resistance
Zbeeb, H., Joumaa, C., Atanasio, G. D. N., Diaspro, A., & Vergani, L. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48070729
“Insulin signaling through InsR activates a downstream signaling cascade [58], which we assessed by measuring AKT phosphorylation at Ser473.”
Fu, M., Singh, M. K., Kim, G., Yoon, K.-S., Kim, S. S., Ha, J., Kang, I., & Choe, W. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27146529
“However, because downstream AKT substrates such as PRAS40, GSK-3 β , FOXO1, TSC2, and S6K1 were not directly assessed, the present data cannot determine whether AKT phosphorylation reflects survival signaling, metabolic feedback, or pathway-specific uncoupling from adipogenesis [49,50].”
Meta-inflammation through the lens of macrophage programming and nutrient-sensing ghrelin signaling
Han, H. W., Kim, D. M., Eshghjoo, S., Xu, C., Liu, Z., Patil, B. S., Guo, S., & Sun, Y. (2026) · Immunometabolism · doi:10.1097/in9.0000000000000088
Madhoun, A. S. A., Malik, M. Z., Albeloushi, S., ABUKHALAF, N. A., Miranda, L., Jacob, S., Nizam, R., John, S., GEORGE, P., Channanath, A. M., et al. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-026-06275-1
“Furthermore, the upregulation of PI3K-AKT-mTOR signaling in all KO models mimics the adaptive responses observed in human diabetic liver [55, 56], indicative of possible resistance mechanisms to GCGR-based therapies.”
Lone, S., Bhat, M. H., Khan, M., & Majid, S. (2026) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-026-01429-1
Leone, L., Kiernan, T. J., Kuwabara, S., Barnett, M. H., Devenney, E. M., Ahmed, R. M., & Lin, C. S.-Y. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1824840
“Derangement in these pathways leads to a transition in APP cleavage from non-amyloidogenic breakdown to amyloidogenic breakdown, contributing to central A β accumulation through both reduced clearance and increased production of A β (21, 22).”
Non-receptor tyrosine kinase signaling pathways and therapeutic implications
Hossain, M. D. A., Cuoco, C. M., Sodaye, S. H., Beci, J., & Belkas, K. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02729-x
“80,203 The PI3K/Akt pathway is damaged in various tissues, leading to obesity and type 2 diabetes due to its role in insulin resistance.”
InfluentialRefractory Diabetic Ketoacidosis Associated with Enfortumab Vedotin
Patel, S. K., Purzycki, T., Mahmoud, A., & Saldarini, J. (2026) · Kidney360 · doi:10.34067/kid.0000001262
Gu, X., Zhang, Y., Li, Y. W., Li, X., Sun, Y., Ma, S., Qin, X., Huang, Y., Shen, X., Zheng, M., et al. (2026) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-026-03758-8
“Isotope tracing experiments further confirmed that 5’-tiRNA Gly increases citrate production via α-KG-dependent reductive carboxylation, activating the PI3K/ Akt/mTOR pathway and promoting lipogenesis [21, 35–37].”
Sammad, A., Qin, J.-F., Meng, D., Khan, S., Zhu, X., & Yin, K. (2026) · Functional & Integrative Genomics · doi:10.1007/s10142-026-01930-z
“PI3K/AKT signaling pathway is required for normal metab - olism due to its characteristics, and its imbalance leads to the development of obesity, type 2 diabetes mellitus, and atherosclerosis (Huang et al. 2018 , Zhao et al. 2021 ).”
Zeinhom, A., Mohamed, A. Y., Abdelaziz, N., Diab, M. S., Salem, A. M. H., Yassen, N. N., Mohammed, E. E. A., Mohamed, A. M., Eid, O. M., Hussein, S. H., et al. (2026) · Stem Cell Reviews and Reports · doi:10.1007/s12015-026-11164-y
“These pathways collectively governed insulin signaling and metabolic control [32–37 ].”
The mechanism of Huanglian-Wendan decoction in treating PCOS-IR based on PI3K-AKT-GSK3 pathway
Wen, Y., Chang, H., Liu, L., Zhang, D., & Wang, M. (2026) · Journal of Radiation Research and Applied Sciences · doi:10.1016/j.jrras.2026.102469
Wang, W., Gao, K., Li, G.-T., Li, K.-C., Liu, S., Yu, H.-H., & Xing, R. (2026) · Carbohydrate Research · doi:10.1016/j.carres.2026.110005
Rongkard, P., Kronsteiner, B., Eckold, C., Chamnan, P., Chumseng, S., Ali, M., Hill, J. W., Abraham, P., Marchi, E., Limmathurotsakul, D., et al. (2026) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofag286
“This signaling pathway regulates many cellular functions, such as glucose metabolism, apoptosis, and immune response [38], and PI3K-Akt dysfunction impairs phagocyte function in sepsis [39].”
Katiyar, S., Ahmad, S., Bhatt, H., Bisen, A. C., Jaiswal, A. K., Ahmad, I., Kushawaha, A. K., Chhikara, N., Baghel, R., Kumar, P., et al. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.110110
Jung, U. J., & Kim, S. R. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27114753
“In addition to its effects on hepatic glucose metabolism, fucoidan also markedly reduced fatty acid-induced lipid deposition in hepatocyte-like spheroid models and HepG2 cells [165].”
Арманович, А. А., Trofimenko, A. I., Jndoyan, Z., Karsian, S. M., Sivaraman, V., Mirzoyan, L. R., Aghajanova, E., Urazova, O. I., Kakturskiy, L., & Вачиковна, П. Н. (2026) · Innovative medicine of Kuban · doi:10.35401/2541-9897-2026-11-2-93-100
Wang, G., Li, Y., Wang, B.-W., Wang, R., Wang, Y., Shu, Y.-B., Zhang, W.-B., Wu, P., Hu, Y., Lu, W., et al. (2026) · The FASEB Journal · doi:10.1096/fj.202600023rr
“The PI3K/AKT pathway is a critical signaling axis that regulates cell survival, metabolism, and stress responses [28–30].”
Wu, L., Meng, Q., & Zhou, Y. (2026) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2026.1775065
“This pathway, PI3K/AKT, is critically involved in both insulin receptor signaling and cancer cell survival (Huang et al., 2018).”
Negrea, G., Balacescu, L., Pavel, I.-O., Sesarman, A., & Banciu, M. (2026) · Scientific Reports · doi:10.1038/s41598-026-52873-1
Ismail, M., Gong, J., Marshall, V. D., Farris, K. B., & Mackler, E. R. (2026) · Journal of Oncology Pharmacy Practice · doi:10.1177/10781552261451729
Lu, K., Li, G.-A., Wang, Y.-J., & Huang, J. (2026) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-026-02188-y
“Obesity and T2DM are major global epidemic metabolic disorders that influence several organs and are characterized by hyperglycemia, which contributes to cardiovascular disease, microangiopathy, renal failure, and stroke [3].”
Xue, C., Li, Z., Yao, L., Zhou, Y., Xiao, Y., Fan, X., Song, D., Chen, W., Ji, D., Wang, Z., et al. (2026) · npj Science of Food · doi:10.1038/s41538-026-00890-9
“Building on evidence that PI3K – AKT signalling is closely linked to insulin sensitivity 15 – 17 and that fructans/fructo-oligosaccharides can remodel the gut microbiota, elevate short-chain fatty acids (SCFAs), and reinforce barrier function, we hypothesized that PRP-W-1 may improve glucose…”
Ameen, O., Sweed, E., Kora, M. A., Kenawy, A., Khalil, M. M., & Khodir, S. A. (2026) · Naunyn-Schmiedeberg's Archives of Pharmacology · doi:10.1007/s00210-026-05407-5
“Diabetes-induced insulin resistance and oxidative stress suppress PI3K activity, leading to Akt and mTOR inactivation, impaired GLUT4 translocation, reduced glycogen synthesis, and increased apoptosis (Huang et al. 2018).”
Long noncoding RNAs in insulin signaling: mechanisms, metabolic roles, and therapeutic prospects
Bhattacharyya, S., Choudhury, D., Vedeshachaitanya, B., & Malakar, P. (2026) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2026.113320
Yang, X., Hu, R.-Z., Shi, M., Yuan, X., Liu, M., Chen, L., Zhang, H.-F., Fan, Z., He, X., He, J.-H., et al. (2026) · Food Frontiers · doi:10.1002/fft2.70289
Krishnan, M., & Babu, S. (2026) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.70500
“Huang (2018) suggests that the primary effector mechanism triggered by insulin in the liver, adipose tissue, and skeletal muscle is the PI3K/AKT pathway [ 75 ].”
Guo, T., Xing, B., Nie, R., Wang, W.-W., Liu, N., An, X., Qi, J.-W., & Wang, Y. (2026) · Food Chemistry: Molecular Sciences · doi:10.1016/j.fochms.2026.100416
“In addition, phospholipid-related signalling molecules, such as PIP2 and PIP3, are known to participate in PI3K-Akt pathway activation (Huang et al., 2018; Liu et al., 2025).”
Woramongkolchai, N., Chaotham, C., Suriya, U., Khine, H. E. E., Poungcho, P., Ariyachet, C., Yen, C.-H., & Chansriniyom, C. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27093914
Molecular and Cellular Mechanisms of Anti‐Obesity Agents: An Integrative Review
Kaur, H., Kaushik, D., Rasane, P., Oz, F., Proestos, C., & Kumar, M. S. A. K. (2026) · The FASEB Journal · doi:10.1096/fj.202600683r
Parikh, R., Thirugnanasambandam, R., & Shah, U. (2026) · Blood Cancer Journal · doi:10.1038/s41408-026-01504-z
“Activation of PI3K /AKT signaling has been observed in MM, and this pathway may be further ampli fi ed in diabetic patients, providing a mechanistic link between metabolic dysregulation and plasma cell malignancy [91, 92].”
Metadata
- 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
- Venue
- International Journal of Biological Sciences
- Publisher
- Ivyspring International Publisher
- Published
- 2018
- Volume
- 14
- Issue
- 11
- Pages
- 1483-1496
- ISSN
- 1449-2288 (ISSN-L)
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
