Toward the Decipherment of Molecular Interactions in the Diabetic Brain

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2022 Jan 21

PMID 35052794

Authors

Maria Chomova

Affiliations

Soon will be listed here.

Abstract

Diabetes mellitus (DM) has been associated with cognitive complications in the brain resulting from acute and chronic metabolic disturbances happening peripherally and centrally. Numerous studies have reported on the morphological, electrophysiological, biochemical, and cognitive changes in the brains of diabetic individuals. The detailed pathophysiological mechanisms implicated in the development of the diabetic cognitive phenotype remain unclear due to intricate molecular changes evolving over time and space. This review provides an insight into recent advances in understanding molecular events in the diabetic brain, focusing on cerebral glucose and insulin uptake, insulin action in the brain, and the role of the brain in the regulation of glucose homeostasis. Fully competent mitochondria are essential for energy metabolism and proper brain function; hence, the potential contribution of mitochondria to the DM-induced impairment of the brain is also discussed.

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References

Chowdhury S, Saleh A, Akude E, Smith D, Morrow D, Tessler L . Ciliary neurotrophic factor reverses aberrant mitochondrial bioenergetics through the JAK/STAT pathway in cultured sensory neurons derived from streptozotocin-induced diabetic rodents. Cell Mol Neurobiol. 2014; 34(5):643-9. PMC: 11488881. DOI: 10.1007/s10571-014-0054-9. View

Morton G, Muta K, Kaiyala K, Rojas J, Scarlett J, Matsen M . Evidence That the Sympathetic Nervous System Elicits Rapid, Coordinated, and Reciprocal Adjustments of Insulin Secretion and Insulin Sensitivity During Cold Exposure. Diabetes. 2017; 66(4):823-834. PMC: 5360298. DOI: 10.2337/db16-1351. View

Tyagi A, Mirita C, Taher N, Shah I, Moeller E, Tyagi A . Metabolic syndrome exacerbates amyloid pathology in a comorbid Alzheimer's mouse model. Biochim Biophys Acta Mol Basis Dis. 2020; 1866(10):165849. PMC: 8421117. DOI: 10.1016/j.bbadis.2020.165849. View

Huang S, Wang Y, Gan X, Fang D, Zhong C, Wu L . Drp1-mediated mitochondrial abnormalities link to synaptic injury in diabetes model. Diabetes. 2014; 64(5):1728-42. PMC: 4407851. DOI: 10.2337/db14-0758. View

Dsouza A, Neumann U, Glavas M, Kieffer T . The glucoregulatory actions of leptin. Mol Metab. 2017; 6(9):1052-1065. PMC: 5605734. DOI: 10.1016/j.molmet.2017.04.011. View

Tooke B, Yu H, Adams J, Jones G, Sutton-Kennedy T, Mundada L . Hypothalamic POMC or MC4R deficiency impairs counterregulatory responses to hypoglycemia in mice. Mol Metab. 2018; 20:194-204. PMC: 6358536. DOI: 10.1016/j.molmet.2018.11.004. View

Erichsen J, Calva C, Reagan L, Fadel J . Intranasal insulin and orexins to treat age-related cognitive decline. Physiol Behav. 2021; 234:113370. PMC: 8053680. DOI: 10.1016/j.physbeh.2021.113370. View

da Silva A, Hall J, do Carmo J . Leptin reverses hyperglycemia and hyperphagia in insulin deficient diabetic rats by pituitary-independent central nervous system actions. PLoS One. 2017; 12(11):e0184805. PMC: 5708697. DOI: 10.1371/journal.pone.0184805. View

Kondo T, Hafezi-Moghadam A, Thomas K, Wagner D, Kahn C . Mice lacking insulin or insulin-like growth factor 1 receptors in vascular endothelial cells maintain normal blood-brain barrier. Biochem Biophys Res Commun. 2004; 317(2):315-20. DOI: 10.1016/j.bbrc.2004.03.043. View

10.

Marseglia A, Fratiglioni L, Laukka E, Santoni G, Pedersen N, Backman L . Early Cognitive Deficits in Type 2 Diabetes: A Population-Based Study. J Alzheimers Dis. 2016; 53(3):1069-78. PMC: 4981902. DOI: 10.3233/JAD-160266. View

11.

Haigh J, New L, Filippi B . Mitochondrial Dynamics in the Brain Are Associated With Feeding, Glucose Homeostasis, and Whole-Body Metabolism. Front Endocrinol (Lausanne). 2020; 11:580879. PMC: 7680879. DOI: 10.3389/fendo.2020.580879. View

12.

Liyanagamage D, Martinus R . Role of Mitochondrial Stress Protein HSP60 in Diabetes-Induced Neuroinflammation. Mediators Inflamm. 2020; 2020:8073516. PMC: 7201845. DOI: 10.1155/2020/8073516. View

13.

Cardoso S, Seica R, Moreira P . Uncoupling Protein 2 Inhibition Exacerbates Glucose Fluctuation-Mediated Neuronal Effects. Neurotox Res. 2017; 33(2):388-401. DOI: 10.1007/s12640-017-9805-y. View

14.

Lin A, Northam E, Rankins D, Werther G, Cameron F . Neuropsychological profiles of young people with type 1 diabetes 12 yr after disease onset. Pediatr Diabetes. 2010; 11(4):235-43. DOI: 10.1111/j.1399-5448.2009.00588.x. View

15.

Abdul-Rahman O, Sasvari-Szekely M, Ver A, Rosta K, Szasz B, Kereszturi E . Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2 diabetic rats. BMC Genomics. 2012; 13:81. PMC: 3299604. DOI: 10.1186/1471-2164-13-81. View

16.

Sivitz W, Walsh S, Morgan D, Donohoue P, Haynes W, Leibel R . Plasma leptin in diabetic and insulin-treated diabetic and normal rats. Metabolism. 1998; 47(5):584-91. DOI: 10.1016/s0026-0495(98)90244-x. View

17.

Guillod-Maximin E, Lorsignol A, Alquier T, Penicaud L . Acute intracarotid glucose injection towards the brain induces specific c-fos activation in hypothalamic nuclei: involvement of astrocytes in cerebral glucose-sensing in rats. J Neuroendocrinol. 2004; 16(5):464-71. DOI: 10.1111/j.1365-2826.2004.01185.x. View

18.

do Carmo J, da Silva A, Ebaady S, Sessums P, Abraham R, Elmquist J . Shp2 signaling in POMC neurons is important for leptin's actions on blood pressure, energy balance, and glucose regulation. Am J Physiol Regul Integr Comp Physiol. 2014; 307(12):R1438-47. PMC: 4269667. DOI: 10.1152/ajpregu.00131.2014. View

19.

Taha E, Ono K, Eguchi T . Roles of Extracellular HSPs as Biomarkers in Immune Surveillance and Immune Evasion. Int J Mol Sci. 2019; 20(18). PMC: 6770223. DOI: 10.3390/ijms20184588. View

20.

Siewiera K, Kassassir H, Talar M, Wieteska L, Watala C . Higher mitochondrial potential and elevated mitochondrial respiration are associated with excessive activation of blood platelets in diabetic rats. Life Sci. 2016; 148:293-304. DOI: 10.1016/j.lfs.2016.02.030. View