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Amyloid-β Induces Hepatic Insulin Resistance by Activating JAK2/STAT3/SOCS-1 Signaling Pathway

Zhang, Yi, Zhou, Ben, Zhang, Fang, Wu, Jingxia, Hu, Yanan, Liu, Yang, Zhai, Qiwei·2012·Diabetes
DOI 10.2337/db11-0499PMC PMC3357286
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Abstract

Epidemiological studies indicate that patients with Alzheimer’s disease (AD) have an increased risk of developing type 2 diabetes mellitus (T2DM), and experimental studies suggest that AD exacerbates T2DM, but the underlying mechanism is still largely unknown. This study aims to investigate whether amyloid-β (Aβ), a key player in AD pathogenesis, contributes to the development of insulin resistance, as well as the underlying mechanism. We find that plasma Aβ40/42 levels are increased in patients with hyperglycemia. APPswe/PSEN1dE9 transgenic AD model mice with increased plasma Aβ40/42 levels show impaired glucose and insulin tolerance and hyperinsulinemia. Furthermore, Aβ impairs insulin signaling in mouse liver and cultured hepatocytes. Aβ can upregulate suppressors of cytokine signaling (SOCS)-1, a well-known insulin signaling inhibitor. Knockdown of SOCS-1 alleviates Aβ-induced impairment of insulin signaling. Moreover, JAK2/STAT3 is activated by Aβ, and inhibition of JAK2/STAT3 signaling attenuates Aβ-induced upregulation of SOCS-1 and insulin resistance in hepatocytes. Our results demonstrate that Aβ induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM.

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  • SOCS-1 is upregulated by Aβ via the JAK2/STAT3 pathway, leading to insulin resistance.

    “SOCS‐1 is upregulated by Aβ via the JAK2/STAT3 pathway, leading to insulin resistance.”

    From BACE1: More than just a β‐secretase (2022) · cites this paper as [96]

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Research works printed but not linked: 40

  1. Stumvoll, 2005, Type 2 diabetes: principles of pathogenesis and therapy, Lancet, 365, 1333, 10.1016/S0140-6736(05)61032-X · DOI · Paper page
  2. Craft, 1992, Glucose and memory in mild senile dementia of the Alzheimer type, J Clin Exp Neuropsychol, 14, 253, 10.1080/01688639208402827 · DOI
  3. Takeda, 2010, Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes, Proc Natl Acad Sci USA, 107, 7036, 10.1073/pnas.1000645107 · DOI
  4. Citron, 2010, Alzheimer’s disease: strategies for disease modification, Nat Rev Drug Discov, 9, 387, 10.1038/nrd2896 · DOI
  5. Xie, 2002, Alzheimer’s beta-amyloid peptides compete for insulin binding to the insulin receptor, J Neurosci, 22, RC221, 10.1523/JNEUROSCI.22-10-j0001.2002 · DOI · Paper page
  6. Qiu, 2006, Insulin, insulin-degrading enzyme and amyloid-beta peptide in Alzheimer’s disease: review and hypothesis, Neurobiol Aging, 27, 190, 10.1016/j.neurobiolaging.2005.01.004 · DOI
  7. Takeda, 2011, Molecular mechanisms linking diabetes mellitus and Alzheimer disease: beta-amyloid peptide, insulin signaling, and neuronal function, Mol Biosyst, 7, 1822, 10.1039/c0mb00302f · DOI
  8. DeMattos, 2002, Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium in a mouse model of Alzheimer’s disease, J Neurochem, 81, 229, 10.1046/j.1471-4159.2002.00889.x · DOI
  9. Roher, 2009, Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer’s disease, Alzheimers Dement, 5, 18, 10.1016/j.jalz.2008.10.004 · DOI
  10. Lee, 2008, Amyloid precursor protein expression is upregulated in adipocytes in obesity, Obesity (Silver Spring), 16, 1493, 10.1038/oby.2008.267 · DOI
  11. Balakrishnan, 2005, Plasma Abeta42 correlates positively with increased body fat in healthy individuals, J Alzheimers Dis, 8, 269, 10.3233/JAD-2005-8305 · DOI
  12. Lee, 2009, Plasma amyloid-beta peptide levels correlate with adipocyte amyloid precursor protein gene expression in obese individuals, Neuroendocrinology, 90, 383, 10.1159/000235555 · DOI
  13. Valdes, 1991, Intravenous glucose tolerance test-derived insulin sensitivity changes during the menstrual cycle, J Clin Endocrinol Metab, 72, 642, 10.1210/jcem-72-3-642 · DOI
  14. Wang, 2009, Abrogation of hepatic ATP-citrate lyase protects against fatty liver and ameliorates hyperglycemia in leptin receptor-deficient mice, Hepatology, 49, 1166, 10.1002/hep.22774 · DOI
  15. Sun, 2007, SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B, Cell Metab, 6, 307, 10.1016/j.cmet.2007.08.014 · DOI · Paper page
  16. Wang, 2008, JAK2/STAT2/STAT3 are required for myogenic differentiation, J Biol Chem, 283, 34029, 10.1074/jbc.M803012200 · DOI
  17. Wan, 2010, Tyk2/STAT3 signaling mediates beta-amyloid-induced neuronal cell death: implications in Alzheimer’s disease, J Neurosci, 30, 6873, 10.1523/JNEUROSCI.0519-10.2010 · DOI
  18. Kim, 2010, A relationship between Alzheimer’s disease and type 2 diabetes mellitus through the measurement of serum amyloid-beta autoantibodies, J Alzheimers Dis, 19, 1371, 10.3233/JAD-2010-1332 · DOI
  19. Jankowsky, 2004, Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase, Hum Mol Genet, 13, 159, 10.1093/hmg/ddh019 · DOI · Paper page
  20. Burgess, 2006, Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer’s disease mouse models with abundant A beta in plasma, Neurobiol Dis, 24, 114, 10.1016/j.nbd.2006.06.007 · DOI · Paper page
  21. Pike, 1995, Structure-activity analyses of beta-amyloid peptides: contributions of the beta 25-35 region to aggregation and neurotoxicity, J Neurochem, 64, 253, 10.1046/j.1471-4159.1995.64010253.x · DOI · Paper page
  22. Hotamisligil, 2006, Inflammation and metabolic disorders, Nature, 444, 860, 10.1038/nature05485 · DOI · Paper page
  23. Rønn, 2007, Diabetes and suppressors of cytokine signaling proteins, Diabetes, 56, 541, 10.2337/db06-1068 · DOI
  24. Ueki, 2004, Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse, Proc Natl Acad Sci USA, 101, 10422, 10.1073/pnas.0402511101 · DOI
  25. Liu, 2004, Longitudinal observation on CSF Abeta42 levels in young to middle-aged amyloid precursor protein/presenilin-1 doubly transgenic mice, Neurobiol Dis, 17, 516, 10.1016/j.nbd.2004.08.005 · DOI
  26. Chiba, 2009, Amyloid-beta causes memory impairment by disturbing the JAK2/STAT3 axis in hippocampal neurons, Mol Psychiatry, 14, 206, 10.1038/mp.2008.105 · DOI · Paper page
  27. Assini, 2004, Plasma levels of amyloid beta-protein 42 are increased in women with mild cognitive impairment, Neurology, 63, 828, 10.1212/01.WNL.0000137040.64252.ED · DOI
  28. Fukumoto, 2003, Age but not diagnosis is the main predictor of plasma amyloid beta-protein levels, Arch Neurol, 60, 958, 10.1001/archneur.60.7.958 · DOI
  29. Cao, 2007, Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease, J Biol Chem, 282, 36275, 10.1074/jbc.M703561200 · DOI · Paper page
  30. Ho, 2004, Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer’s disease, FASEB J, 18, 902, 10.1096/fj.03-0978fje · DOI
  31. Kahn, 2006, Mechanisms linking obesity to insulin resistance and type 2 diabetes, Nature, 444, 840, 10.1038/nature05482 · DOI · Paper page
  32. Kypreos, 2009, Mechanisms of obesity and related pathologies: role of apolipoprotein E in the development of obesity, FEBS J, 276, 5720, 10.1111/j.1742-4658.2009.07301.x · DOI
  33. Thirumangalakudi, 2008, High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice, J Neurochem, 106, 475, 10.1111/j.1471-4159.2008.05415.x · DOI · Paper page
  34. Meakin, 2012, Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice, Biochem J, 441, 285, 10.1042/BJ20110512 · DOI · Paper page
  35. Chen, 2006, Distinct early folding and aggregation properties of Alzheimer amyloid-beta peptides Abeta40 and Abeta42: stable trimer or tetramer formation by Abeta42, J Biol Chem, 281, 24414, 10.1074/jbc.M602363200 · DOI
  36. Joachim, 1989, Amyloid beta-protein deposition in tissues other than brain in Alzheimer’s disease, Nature, 341, 226, 10.1038/341226a0 · DOI
  37. Mason, 1999, Distribution and fluidizing action of soluble and aggregated amyloid beta-peptide in rat synaptic plasma membranes, J Biol Chem, 274, 18801, 10.1074/jbc.274.26.18801 · DOI
  38. Ueki, 2004, Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms, Mol Cell Biol, 24, 5434, 10.1128/MCB.24.12.5434-5446.2004 · DOI · Paper page
  39. Shimizu, 2008, Hydrogen peroxide stimulates tetrahydrobiopterin synthesis through activation of the Jak2 tyrosine kinase pathway in vascular endothelial cells, Int J Biochem Cell Biol, 40, 755, 10.1016/j.biocel.2007.10.011 · DOI
  40. Liao, 2009, Insulin signaling in sporadic Alzheimer’s disease, Sci Signal, 2, pe36, 10.1126/scisignal.274pe36 · DOI

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Metadata

Authors
Zhang, Y., Zhou, B., Zhang, F., Wu, J., Hu, Y., Liu, Y., & Zhai, Q.
Affiliations
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China
Venue
Diabetes
Publisher
American Diabetes Association
Published
2012-05-14
Volume
61
Issue
6
Pages
1434-1443
ISSN
  • 0012-1797
  • 1939-327X
DOI
10.2337/db11-0499
PMC
PMC3357286
Cited by
92
References
13
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 3392 d)

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