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Intranasal insulin ameliorates tau hyperphosphorylation in a rat model of type 2 diabetes.
J Alzheimers Dis. 2013; 33(2):329-38.JA

Abstract

Recent studies have demonstrated that insulin plays important roles in the brain, including regulation of glucose metabolism and modulation of learning and memory. We have found dysregulation of brain insulin signaling in both Alzheimer's disease (AD) and type 2 diabetes (T2D), which correlates to hyperphosphorylation of tau, a key abnormal tau modification leading to neurofibrillary tangles. Here, we investigated tau phosphorylation and the two key components of the insulin signaling pathway, protein kinase B (AKT) and glycogen synthase kinase-3β (GSK-3β), in a rat model of T2D produced by a high protein, high glucose, and high fat diet followed by intraperitoneal injection of streptozocin. We found tau hyperphosphorylation, decreased AKT activation, and GSK-3β over-activation in T2D rat brains. Intranasal insulin treatment for four weeks normalized AKT and GSK-3β, as well as reduced tau hyperphosphorylation in T2D rat brains, whereas four-week treatments with subcutaneous insulin had minimal effects on brain GSK-3β and tau phosphorylation. These results suggest decreased brain insulin signaling and tau hyperphosphorylation in the rat model of T2D and demonstrate the efficacy of intranasal insulin treatment to reverse these brain abnormalities. Our findings provide further mechanism by which T2D increases the risk for AD and also support the potential use of intranasal insulin for the treatment of AD.

Authors+Show Affiliations

Department of Endocrinology, Tongji Hospital, Tongji Medical College of the Huazhong University of Science and Technology, Wuhan, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22936005

Citation

Yang, Yan, et al. "Intranasal Insulin Ameliorates Tau Hyperphosphorylation in a Rat Model of Type 2 Diabetes." Journal of Alzheimer's Disease : JAD, vol. 33, no. 2, 2013, pp. 329-38.
Yang Y, Ma D, Wang Y, et al. Intranasal insulin ameliorates tau hyperphosphorylation in a rat model of type 2 diabetes. J Alzheimers Dis. 2013;33(2):329-38.
Yang, Y., Ma, D., Wang, Y., Jiang, T., Hu, S., Zhang, M., Yu, X., & Gong, C. X. (2013). Intranasal insulin ameliorates tau hyperphosphorylation in a rat model of type 2 diabetes. Journal of Alzheimer's Disease : JAD, 33(2), 329-38. https://doi.org/10.3233/JAD-2012-121294
Yang Y, et al. Intranasal Insulin Ameliorates Tau Hyperphosphorylation in a Rat Model of Type 2 Diabetes. J Alzheimers Dis. 2013;33(2):329-38. PubMed PMID: 22936005.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intranasal insulin ameliorates tau hyperphosphorylation in a rat model of type 2 diabetes. AU - Yang,Yan, AU - Ma,Delin, AU - Wang,Yuping, AU - Jiang,Teng, AU - Hu,Shuhong, AU - Zhang,Muxun, AU - Yu,Xuefeng, AU - Gong,Cheng-Xin, PY - 2012/9/1/entrez PY - 2012/9/1/pubmed PY - 2013/5/29/medline SP - 329 EP - 38 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 33 IS - 2 N2 - Recent studies have demonstrated that insulin plays important roles in the brain, including regulation of glucose metabolism and modulation of learning and memory. We have found dysregulation of brain insulin signaling in both Alzheimer's disease (AD) and type 2 diabetes (T2D), which correlates to hyperphosphorylation of tau, a key abnormal tau modification leading to neurofibrillary tangles. Here, we investigated tau phosphorylation and the two key components of the insulin signaling pathway, protein kinase B (AKT) and glycogen synthase kinase-3β (GSK-3β), in a rat model of T2D produced by a high protein, high glucose, and high fat diet followed by intraperitoneal injection of streptozocin. We found tau hyperphosphorylation, decreased AKT activation, and GSK-3β over-activation in T2D rat brains. Intranasal insulin treatment for four weeks normalized AKT and GSK-3β, as well as reduced tau hyperphosphorylation in T2D rat brains, whereas four-week treatments with subcutaneous insulin had minimal effects on brain GSK-3β and tau phosphorylation. These results suggest decreased brain insulin signaling and tau hyperphosphorylation in the rat model of T2D and demonstrate the efficacy of intranasal insulin treatment to reverse these brain abnormalities. Our findings provide further mechanism by which T2D increases the risk for AD and also support the potential use of intranasal insulin for the treatment of AD. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/22936005/Intranasal_insulin_ameliorates_tau_hyperphosphorylation_in_a_rat_model_of_type_2_diabetes_ DB - PRIME DP - Unbound Medicine ER -