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Pathophysiology
Glial and Vascular Cell Regulation of the Blood-Brain Barrier in Diabetes
Xiaolong Li, Yan Cai, Zuo Zhang, Jiyin Zhou
Diabetes Metab J. 2022;46(2):222-238.   Published online March 18, 2022
DOI: https://doi.org/10.4093/dmj.2021.0146
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  • 296 Download
  • 12 Web of Science
  • 12 Crossref
AbstractAbstract PDFPubReader   ePub   
As a structural barrier, the blood-brain barrier (BBB) is located at the interface between the brain parenchyma and blood, and modulates communication between the brain and blood microenvironment to maintain homeostasis. The BBB is composed of endothelial cells, basement membrane, pericytes, and astrocytic end feet. BBB impairment is a distinguishing and pathogenic factor in diabetic encephalopathy. Diabetes causes leakage of the BBB through downregulation of tight junction proteins, resulting in impaired functioning of endothelial cells, pericytes, astrocytes, microglia, nerve/glial antigen 2-glia, and oligodendrocytes. However, the temporal regulation, mechanisms of molecular and signaling pathways, and consequences of BBB impairment in diabetes are not well understood. Consequently, the efficacy of therapies diabetes targeting BBB leakage still lags behind the requirements. This review summarizes the recent research on the effects of diabetes on BBB composition and the potential roles of glial and vascular cells as therapeutic targets for BBB disruption in diabetic encephalopathy.

Citations

Citations to this article as recorded by  
  • Gut microbiota and type 2 diabetes mellitus: a focus on the gut-brain axis
    Yi Pan, Tong Bu, Xia Deng, Jue Jia, Guoyue Yuan
    Endocrine.2024; 84(1): 1.     CrossRef
  • Long-Term Exposure of Cultured Astrocytes to High Glucose Impact on Their LPS-Induced Activation
    Ayna Abdyeva, Ekaterina Kurtova, Irina Savinkova, Maksim Galkov, Liubov Gorbacheva
    International Journal of Molecular Sciences.2024; 25(2): 1122.     CrossRef
  • Role of autophagy in angiogenic potential of vascular pericytes
    Soheil Zamen Milani, Aysa Rezabakhsh, Mohammad Karimipour, Leila Salimi, Narges Mardi, Maryam Taghavi Narmi, Fatemeh Sadeghsoltani, Ferzane Valioglu, Reza Rahbarghazi
    Frontiers in Cell and Developmental Biology.2024;[Epub]     CrossRef
  • The NG2-glia is a potential target to maintain the integrity of neurovascular unit after acute ischemic stroke
    Xiaoyan Hu, Panpan Geng, Xiaoyun Zhao, Qian Wang, Changqing Liu, Chun Guo, Wen Dong, Xinchun Jin
    Neurobiology of Disease.2023; 180: 106076.     CrossRef
  • Tight junction disruption and the pathogenesis of the chronic complications of diabetes mellitus: A narrative review
    Ma Ludivina Robles-Osorio, Ernesto Sabath
    World Journal of Diabetes.2023; 14(7): 1013.     CrossRef
  • Function and therapeutic value of astrocytes in diabetic cognitive impairment
    Fanyu Meng, Jiafeng Fu, Lin Zhang, Mengqing Guo, Pengwei Zhuang, Qingsheng Yin, Yanjun Zhang
    Neurochemistry International.2023; 169: 105591.     CrossRef
  • Exploring the molecular targets for Type 2 diabetes-induced Alzheimer’s disease through bioinformatics analysis
    Lin Gao, Chengyu Huang, Hui Li, Shidi Wu, Xiaoyan Zhou, Changjiang Ying
    Epigenomics.2023; 15(11): 619.     CrossRef
  • In vivo retinal imaging is associated with cognitive decline, blood-brain barrier disruption and neuroinflammation in type 2 diabetic mice
    May Majimbi, Samuel McLenachan, Michael Nesbit, Fred K. Chen, Virginie Lam, John Mamo, Ryu Takechi
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Diabetic microvascular disease in non-classical beds: the hidden impact beyond the retina, the kidney, and the peripheral nerves
    Dídac Mauricio, Mònica Gratacòs, Josep Franch-Nadal
    Cardiovascular Diabetology.2023;[Epub]     CrossRef
  • Transcranial photobiomodulation improves insulin therapy in diabetic microglial reactivity and the brain drainage system
    Shaojun Liu, Dongyu Li, Tingting Yu, Jingtan Zhu, Oxana Semyachkina-Glushkovskaya, Dan Zhu
    Communications Biology.2023;[Epub]     CrossRef
  • NG2‐glia crosstalk with microglia in health and disease
    Zuo Zhang, Xiaolong Li, Hongli Zhou, Jiyin Zhou
    CNS Neuroscience & Therapeutics.2022; 28(11): 1663.     CrossRef
  • Accelerated amyloid angiopathy and related vascular alterations in a mixed murine model of Alzheimer´s disease and type two diabetes
    Maria Vargas-Soria, Juan Jose Ramos-Rodriguez, Angel del Marco, Carmen Hierro-Bujalance, Maria Jose Carranza-Naval, Maria Calvo-Rodriguez, Susanne J. van Veluw, Alan W. Stitt, Rafael Simó, Brian J. Bacskai, Carmen Infante-Garcia, Monica Garcia-Alloza
    Fluids and Barriers of the CNS.2022;[Epub]     CrossRef
Original Articles
Complication
Association between Type 2 Diabetes Mellitus and Brain Atrophy: A Meta-Analysis
Tianqi Zhang, Marnie Shaw, Nicolas Cherbuin
Diabetes Metab J. 2022;46(5):781-802.   Published online March 8, 2022
DOI: https://doi.org/10.4093/dmj.2021.0189
  • 6,377 View
  • 296 Download
  • 11 Web of Science
  • 20 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Type 2 diabetes mellitus (T2DM) is known to be associated with cognitive decline and brain structural changes. This study systematically reviews and estimates human brain volumetric differences and atrophy associated with T2DM.
Methods
PubMed, PsycInfo and Cochrane Library were searched for brain imaging studies reporting on brain volume differences between individuals with T2DM and healthy controls. Data were examined using meta-analysis, and association between age, sex, diabetes characteristics and brain volumes were tested using meta-regression.
Results
A total of 14,605 entries were identified; after title, abstract and full-text screening applying inclusion and exclusion criteria, 64 studies were included and 42 studies with compatible data contributed to the meta-analysis (n=31,630; mean age 71.0 years; 44.4% male; 26,942 control; 4,688 diabetes). Individuals with T2DM had significantly smaller total brain volume, total grey matter volume, total white matter volume and hippocampal volume (approximately 1% to 4%); meta-analyses of smaller samples focusing on other brain regions and brain atrophy rate in longitudinal investigations also indicated smaller brain volumes and greater brain atrophy associated with T2DM. Meta-regression suggests that diabetes-related brain volume differences start occurring in early adulthood, decreases with age and increases with diabetes duration.
Conclusion
T2DM is associated with smaller total and regional brain volume and greater atrophy over time. These effects are substantial and highlight an urgent need to develop interventions to reduce the risk of T2DM for brain health.

Citations

Citations to this article as recorded by  
  • Diabetes, antidiabetic medications and risk of dementia: A systematic umbrella review and meta‐analysis
    Alvin Kuate Defo, Veselko Bakula, Alessandro Pisaturo, Christopher Labos, Simon S. Wing, Stella S. Daskalopoulou
    Diabetes, Obesity and Metabolism.2024; 26(2): 441.     CrossRef
  • Cognitive deficits among people with schizophrenia and prediabetes or diabetes
    Alexander Panickacheril John, Thynn Mya, Darren Haywood
    Acta Psychiatrica Scandinavica.2024; 149(1): 65.     CrossRef
  • The association of glucose metabolism measures and diabetes status with Alzheimer’s disease biomarkers of amyloid and tau: A systematic review and meta-analysis
    Veerle van Gils, Marianna Rizzo, Jade Côté, Wolfgang Viechtbauer, Giuseppe Fanelli, Jordi Salas-Salvadó, Theresa Wimberley, Mònica Bulló, Fernando Fernandez-Aranda, Søren Dalsgaard, Pieter Jelle Visser, Willemijn J. Jansen, Stephanie J.B. Vos
    Neuroscience & Biobehavioral Reviews.2024; 159: 105604.     CrossRef
  • ECHDC3 Variant Regulates the Right Hippocampal Microstructural Integrity and Verbal Memory in Type 2 Diabetes Mellitus
    Qiyu Zhao, Xin Du, Feng Liu, Yang Zhang, Wen Qin, Quan Zhang
    Neuroscience.2024; 538: 30.     CrossRef
  • The hemodynamic response function as a type 2 diabetes biomarker: a data-driven approach
    Pedro Guimarães, Pedro Serranho, João V. Duarte, Joana Crisóstomo, Carolina Moreno, Leonor Gomes, Rui Bernardes, Miguel Castelo-Branco
    Frontiers in Neuroinformatics.2024;[Epub]     CrossRef
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    Keon-Joo Lee, Hee-Joon Bae
    Cerebral Circulation - Cognition and Behavior.2024; 6: 100199.     CrossRef
  • Understanding the relationship between type-2 diabetes, MRI markers of neurodegeneration and small vessel disease, and dementia risk: a mediation analysis
    Leslie Grasset, Eric Frison, Catherine Helmer, Gwénaëlle Catheline, Geneviève Chêne, Carole Dufouil
    European Journal of Epidemiology.2024;[Epub]     CrossRef
  • Vulnerability of the Hippocampus to Insults: Links to Blood–Brain Barrier Dysfunction
    Terry L. Davidson, Richard J. Stevenson
    International Journal of Molecular Sciences.2024; 25(4): 1991.     CrossRef
  • The gut microbiota‐astrocyte axis: Implications for type 2 diabetic cognitive dysfunction
    Zi‐Han Li, Ya‐Yi Jiang, Cai‐Yi Long, Qian Peng, Ren‐Song Yue
    CNS Neuroscience & Therapeutics.2023; 29(S1): 59.     CrossRef
  • NHANES 2011–2014 Reveals Decreased Cognitive Performance in U.S. Older Adults with Metabolic Syndrome Combinations
    Edgar Díaz-Camargo, Juan Hernández-Lalinde, María Sánchez-Rubio, Yudy Chaparro-Suárez, Liseth Álvarez-Caicedo, Alexandra Fierro-Zarate, Marbel Gravini-Donado, Henry García-Pacheco, Joselyn Rojas-Quintero, Valmore Bermúdez
    International Journal of Environmental Research and Public Health.2023; 20(7): 5257.     CrossRef
  • People with Diabetes Have Poorer Self-Rated Health (SRH) and Diabetes Moderates the Association between Age and SRH
    Weixi Kang, Antonio Malvaso
    Diseases.2023; 11(2): 73.     CrossRef
  • Cognitive dysfunction in diabetes: abnormal glucose metabolic regulation in the brain
    Shan Zhang, Yueying Zhang, Zhige Wen, YaNan Yang, Tianjie Bu, Xiangwei Bu, Qing Ni
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • The psychological basis of hunger and its dysfunctions
    Richard J Stevenson
    Nutrition Reviews.2023;[Epub]     CrossRef
  • Associations of Glucose Metabolism Status with Brain Macrostructure and Microstructure: Findings from the UK Biobank
    Ruyi Li, Tingting Geng, Lin Li, Qi Lu, Rui Li, Xue Chen, Yunjing Ou, Sen Liu, Xiaoyu Lin, Qingying Tian, Zixin Qiu, Kai Zhu, Ziyue Tang, Kun Yang, An Pan, Gang Liu
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  • Association Between Frequency of Social Contact and Brain Atrophy in Community-Dwelling Older People Without Dementia
    Naoki Hirabayashi, Takanori Honda, Jun Hata, Yoshihiko Furuta, Mao Shibata, Tomoyuki Ohara, Yasuko Tatewaki, Yasuyuki Taki, Shigeyuki Nakaji, Tetsuya Maeda, Kenjiro Ono, Masaru Mimura, Kenji Nakashima, Jun-ichi Iga, Minoru Takebayashi, Toshiharu Ninomiya,
    Neurology.2023;[Epub]     CrossRef
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    Saba Raoof Syed, Saleem Durai M. A.
    Frontiers in Neuroscience.2023;[Epub]     CrossRef
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    Jose A. Santiago, Mridula Karthikeyan, Madison Lackey, Diana Villavicencio, Judith A. Potashkin
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  • Association between Type 2 Diabetes Mellitus and Brain Atrophy: A Meta-Analysis (Diabetes Metab J 2022;46:781-802)
    Tianqi Zhang, Marnie Shaw, Nicolas Cherbuin
    Diabetes & Metabolism Journal.2022; 46(5): 815.     CrossRef
  • Association between Type 2 Diabetes Mellitus and Brain Atrophy: A Meta-Analysis (Diabetes Metab J 2022;46:781-802)
    Se Hee Min
    Diabetes & Metabolism Journal.2022; 46(5): 813.     CrossRef
  • MORPHOFUNCTIONAL CHANGES OF THE BRAIN IN DIABETES MELLITUS
    A. V. Smirnov, A. I Bisinbekova, T. I Faibisovich
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Drug/Regimen
Glucagon-Like Peptide-1 Receptor Agonist Differentially Affects Brain Activation in Response to Visual Food Cues in Lean and Obese Individuals with Type 2 Diabetes Mellitus
Jae Hyun Bae, Hyung Jin Choi, Kang Ik Kevin Cho, Lee Kyung Kim, Jun Soo Kwon, Young Min Cho
Diabetes Metab J. 2020;44(2):248-259.   Published online November 4, 2019
DOI: https://doi.org/10.4093/dmj.2019.0018
  • 7,312 View
  • 222 Download
  • 5 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

To investigate the effects of a glucagon-like peptide-1 receptor agonist on functional brain activation in lean and obese individuals with type 2 diabetes mellitus (T2DM) in response to visual food cues.

Methods

In a randomized, single-blinded, crossover study, 15 lean and 14 obese individuals with T2DM were administered lixisenatide or normal saline subcutaneously with a 1-week washout period. We evaluated brain activation in response to pictures of high-calorie food, low-calorie food, and nonfood using functional magnetic resonance imaging and measured appetite and caloric intake in participants who were given access to an ad libitum buffet.

Results

Obese individuals with T2DM showed significantly greater activation of the hypothalamus, pineal gland, parietal cortex (high-calorie food vs. low-calorie food, P<0.05), orbitofrontal cortex (high-calorie food vs. nonfood, P<0.05), and visual cortex (food vs. nonfood, P<0.05) than lean individuals with T2DM. Lixisenatide injection significantly reduced the functional activation of the fusiform gyrus and lateral ventricle in obese individuals with T2DM compared with that in lean individuals with T2DM (nonfood vs. high-calorie food, P<0.05). In addition, in individuals who decreased their caloric intake after lixisenatide injection, there were significant interaction effects between group and treatment in the posterior cingulate, medial frontal cortex (high-calorie food vs. low-calorie food, P<0.05), hypothalamus, orbitofrontal cortex, and temporal lobe (food vs. nonfood, P<0.05).

Conclusion

Brain responses to visual food cues were different in lean and obese individuals with T2DM. In addition, acute administration of lixisenatide differentially affected functional brain activation in these individuals, especially in those who decreased their caloric intake after lixisenatide injection.

Citations

Citations to this article as recorded by  
  • Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)
    Jae Hyun Bae
    Diabetes & Metabolism Journal.2024; 48(1): 157.     CrossRef
  • Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial
    Natalia McInnes, Stephanie Hall, Heather A. Lochnan, Stewart B. Harris, Zubin Punthakee, Ronald J. Sigal, Irene Hramiak, Mohammed Azharuddin, Joanne F. Liutkus, Jean‐François Yale, Farah Sultan, Ada Smith, Rose E. Otto, Diana Sherifali, Yan Yun Liu, Hertz
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    Hussein Zaitoon, Ronit Lubetzky, Achiya Z. Amir, Hadar Moran-Lev, Liora Sagi, Michal Yacobi-Bach, Ophir Borger, Efrat Chorna, Yael Lebenthal, Avivit Brener
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    Diabetes, Obesity and Metabolism.2021; 23(5): 1202.     CrossRef
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    Xi Guo, Su Wang, Yu-Chen Chen, Heng-Le Wei, Gang-Ping Zhou, Yu-Sheng Yu, Xindao Yin, Kun Wang, Hong Zhang, Eusebio Chiefari
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Diabetes Metab J : Diabetes & Metabolism Journal