title: Curcumin regulates insulin pathways and glucose metabolism in the brains of APPswe/PS1dE9 mice.
abstract: Recent studies have shown the therapeutic potential of curcumin in Alzheimer's disease (AD). In 2014, our lab found that curcumin reduced Aβ40, Aβ42 and Aβ-derived diffusible ligands in the mouse hippocampus, and improved learning and memory. However, the mechanisms underlying this biological effect are only partially known. There is considerable evidence in brain metabolism studies indicating that AD might be a brain-specific type of diabetes with progressive impairment of glucose utilisation and insulin signalling. We hypothesised that curcumin might target both the glucose metabolism and insulin signalling pathways. In this study, we monitored brain glucose metabolism in living APPswe/PS1dE9 double transgenic mice using a micro-positron emission tomography (PET) technique. The study showed an improvement in cerebral glucose uptake in AD mice. For a more in-depth study, we used immunohistochemical (IHC) staining and western blot techniques to examine key factors in both glucose metabolism and brain insulin signalling pathways. The results showed that curcumin ameliorated the defective insulin signalling pathway by upregulating insulin-like growth factor (IGF)-1R, IRS-2, PI3K, p-PI3K, Akt and p-Akt protein expression while downregulating IR and IRS-1. Our study found that curcumin improved spatial learning and memory, at least in part, by increasing glucose metabolism and ameliorating the impaired insulin signalling pathways in the brain.
authors.affiliation: 1 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.|2 Key Laboratory of Pharmacology of Dongzhimen Hospital (BUCM), State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Pengwen
authors.initials: P
authors.lastname: Wang
authors.affiliation: 3 Department of Surgery (Neurosurgery, Neurobiology) and Hamilton NeuroRestorative Group, McMaster University, Health Sciences Centre, Hamilton, ON, Canada.
authors.forename: Caixin
authors.initials: C
authors.lastname: Su
authors.affiliation: 1 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.|2 Key Laboratory of Pharmacology of Dongzhimen Hospital (BUCM), State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Feng
authors.affiliation: 1 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.|4 Kaifeng Hospital of Traditional Chinese Medicine, Kaifeng, China.
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Chen
authors.affiliation: 1 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.|2 Key Laboratory of Pharmacology of Dongzhimen Hospital (BUCM), State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Dong
authors.affiliation: 5 Mizumori Lab, Department of Psychology, University of Washington, Seattle, WA, USA.
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Rao
authors.affiliation: 1 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.|2 Key Laboratory of Pharmacology of Dongzhimen Hospital (BUCM), State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ren
authors.affiliation: 1 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.|2 Key Laboratory of Pharmacology of Dongzhimen Hospital (BUCM), State Administration of Traditional Chinese Medicine, Beijing, China.
authors.forename: Jinduo
authors.initials: J
authors.lastname: Yang
authors.affiliation: 1 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.|6 Beijing University of Chinese Medicine, BUCM Neurology Center, Dongzhimen Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: 1 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.|6 Beijing University of Chinese Medicine, BUCM Neurology Center, Dongzhimen Hospital, Beijing, China.
authors.forename: Jinzhou
authors.initials: J
authors.lastname: Tian
authors.affiliation: 3 Department of Surgery (Neurosurgery, Neurobiology) and Hamilton NeuroRestorative Group, McMaster University, Health Sciences Centre, Hamilton, ON, Canada.
authors.forename: Shucui
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D065853:Spatial Learning / Q000187:drug effects
chemical_list: D016564:Amyloid beta-Protein Precursor; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse; D017451:Receptors, Somatomedin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin; D005947:Glucose
keywords: APPswe/PS1dE9 double transgenic mice; Alzheimer’s disease; IGF-1R; brain glucose metabolism; curcumin; insulin signalling pathway