Editorial: molecular mechanism of neuronal dysfunction in the diabetic brain

The Editorial on the Research Topic

Molecular Mechanism of Neuronal Dysfunction in the Diabetic Brain

Insulin signaling plays a significant role in the brain synaptic function. Insulin resistance is associated with reductions in cerebral glucose metabolism even in prediabetic individuals ( 1 ). Cognitive dysfunction in chronic diabetes is being recognized as a complication that needs to be seriously addressed. Epidemiological studies have also identified diabetes as a risk factor for Alzheimer’s disease (AD) ( 2 , 3 ). The link between diabetes and AD is further supported by studies in animal models ( 3 ). Chronic hyperglycemia-induced accumulation of advanced glycation end products (AGEs) ( 4 ) and their receptor RAGE are among the mechanistic links between diabetes and AD ( 5 ). Soluble form of RAGE (sRAGE) acts as a decoy for RAGE and provides a counter-regulatory mechanism. Selvin et al. have reported that low levels of sRAGE increase the risk of diabetes and mortality ( 6 ). Decreased levels of sRAGE have been also observed in AD patients ( 7 ). In this special issue, six articles (three original reports and three reviews) highlight the interactions of these two aging-associated diseases from several angles.

2. Huang CC, Chung CM, Leu HB, Lin LY, Chiu CC, Hsu CY, et al. Diabetes mellitus and the risk of Alzheimer’s disease: a nationwide population-based study. PLoS One (2014)9 : e87095. doi: 10. 1371/journal. pone. 0087095

3. Ott A, Stolk R, Harskamp F. v., Pols H, Hoffman A, Breteler M. Diabetes mellitus and the risk of dementia. The Rotterdam study. Neurology (1999)53 : 1937–42. doi: 10. 1212/WNL. 53. 9. 1937

4. Goh SY, Cooper ME. Clinical review: the role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab (2008)93 : 1143–52. doi: 10. 1210/jc. 2007-1817

5. Srikanth V, Maczurek A, Phan T, Steele M, Westcott B, Juskiw D, et al. Advanced glycation endproducts and their receptor RAGE in Alzheimer’s disease. Neurobiol Aging (2011)32 : 763–77. doi: 10. 1016/j. neurobiolaging. 2009. 04. 016

6. Selvin E, Halushka MK, Rawlings AM, Hoogeveen RC, Ballantyne CM, Coresh J, et al. sRAGE and risk of diabetes, cardiovascular disease, and death. Diabetes (2013)62 : 2116–21. doi: 10. 2337/db12-1528

7. Liang F, Jia J, Wang S, Qin W, Liu G. Decreased plasma levels of soluble low density lipoprotein receptor-related protein-1 (sLRP) and the soluble form of the receptor for advanced glycation end products (sRAGE) in the clinical diagnosis of Alzheimer’s disease. J Clin Neurosci (2013)20 : 357–61. doi: 10. 1016/j. jocn. 2012. 06. 005

8. Vinik AI, Maser RE, Ziegler D. Autonomic imbalance: prophet of doom or scope for hope? Diabet Med (2011)28 : 643–51. doi: 10. 1111/j. 1464-5491. 2010. 03184. x

9. Velmurugan K, Bouchard R, Mahaffey G, Pugazhenthi S. Neuroprotective actions of glucagon-like peptide-1 in differentiated human neuroprogenitor cells. J Neurochem (2012)123 : 919–31. doi: 10. 1111/jnc. 12036