Tags

Type your tag names separated by a space and hit enter

Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer's disease.
Biochim Biophys Acta 2009; 1792(5):482-96BB

Abstract

Characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system respectively, it is now widely recognized that type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share several common abnormalities including impaired glucose metabolism, increased oxidative stress, insulin resistance and amyloidogenesis. Several recent studies suggest that this is not an epiphenomenon, but rather these two diseases disrupt common molecular pathways and each disease compounds the progression of the other. For instance, in AD the accumulation of the amyloid-beta peptide (Abeta), which characterizes the disease and is thought to participate in the neurodegenerative process, may also induce neuronal insulin resistance. Conversely, disrupting normal glucose metabolism in transgenic animal models of AD that over-express the human amyloid precursor protein (hAPP) promotes amyloid-peptide aggregation and accelerates the disease progression. Studying these processes at a cellular level suggests that insulin resistance and Abeta aggregation may not only be the consequence of excitotoxicity, aberrant Ca(2+) signals, and proinflammatory cytokines such as TNF-alpha, but may also promote these pathological effectors. At the molecular level, insulin resistance and Abeta disrupt common signal transduction cascades including the insulin receptor family/PI3 kinase/Akt/GSK3 pathway. Thus both disease processes contribute to overlapping pathology, thereby compounding disease symptoms and progression.

Authors+Show Affiliations

Alzheimer's Research, Merck Research Laboratories, West Point, PA 19486, USA. wei-quin_zhao@merck.comNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

19026743

Citation

Zhao, Wei-Qin, and Matthew Townsend. "Insulin Resistance and Amyloidogenesis as Common Molecular Foundation for Type 2 Diabetes and Alzheimer's Disease." Biochimica Et Biophysica Acta, vol. 1792, no. 5, 2009, pp. 482-96.
Zhao WQ, Townsend M. Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer's disease. Biochim Biophys Acta. 2009;1792(5):482-96.
Zhao, W. Q., & Townsend, M. (2009). Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer's disease. Biochimica Et Biophysica Acta, 1792(5), pp. 482-96. doi:10.1016/j.bbadis.2008.10.014.
Zhao WQ, Townsend M. Insulin Resistance and Amyloidogenesis as Common Molecular Foundation for Type 2 Diabetes and Alzheimer's Disease. Biochim Biophys Acta. 2009;1792(5):482-96. PubMed PMID: 19026743.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer's disease. AU - Zhao,Wei-Qin, AU - Townsend,Matthew, Y1 - 2008/11/05/ PY - 2008/08/03/received PY - 2008/10/18/revised PY - 2008/10/21/accepted PY - 2008/11/26/pubmed PY - 2009/7/8/medline PY - 2008/11/26/entrez SP - 482 EP - 96 JF - Biochimica et biophysica acta JO - Biochim. Biophys. Acta VL - 1792 IS - 5 N2 - Characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system respectively, it is now widely recognized that type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share several common abnormalities including impaired glucose metabolism, increased oxidative stress, insulin resistance and amyloidogenesis. Several recent studies suggest that this is not an epiphenomenon, but rather these two diseases disrupt common molecular pathways and each disease compounds the progression of the other. For instance, in AD the accumulation of the amyloid-beta peptide (Abeta), which characterizes the disease and is thought to participate in the neurodegenerative process, may also induce neuronal insulin resistance. Conversely, disrupting normal glucose metabolism in transgenic animal models of AD that over-express the human amyloid precursor protein (hAPP) promotes amyloid-peptide aggregation and accelerates the disease progression. Studying these processes at a cellular level suggests that insulin resistance and Abeta aggregation may not only be the consequence of excitotoxicity, aberrant Ca(2+) signals, and proinflammatory cytokines such as TNF-alpha, but may also promote these pathological effectors. At the molecular level, insulin resistance and Abeta disrupt common signal transduction cascades including the insulin receptor family/PI3 kinase/Akt/GSK3 pathway. Thus both disease processes contribute to overlapping pathology, thereby compounding disease symptoms and progression. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/19026743/Insulin_resistance_and_amyloidogenesis_as_common_molecular_foundation_for_type_2_diabetes_and_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0925-4439(08)00209-3 DB - PRIME DP - Unbound Medicine ER -