Format

Send to

Choose Destination
Arch Neurol. 2005 Oct;62(10):1539-44.

Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults.

Author information

1
Department of Neurology, University of Washington, Seattle, WA 98108, USA.

Abstract

BACKGROUND:

Inflammation has been implicated as a pathogenetic factor in Alzheimer disease, possibly via effects on beta-amyloid (Abeta). Hyperinsulinemia induces inflammation and is a risk factor for Alzheimer disease. Thus, insulin abnormalities may contribute to Alzheimer disease pathophysiology through effects on the inflammatory network.

OBJECTIVES:

To determine the effects of induced hyperinsulinemia with euglycemia on Abeta, transthyretin, and inflammatory markers and modulators in plasma and cerebrospinal fluid (CSF).

DESIGN:

Randomized crossover trial.

SETTING:

Veterans Affairs hospital clinical research unit.

PARTICIPANTS:

Sixteen healthy adults ranging from 55 to 81 years of age (mean age, 68.2 years).

INTERVENTIONS:

On separate mornings, fasting participants received randomized infusions of saline or insulin (1.0 mU.kg(-1).min(-1)) with variable dextrose levels to maintain euglycemia, achieving plasma insulin levels typical of insulin resistance. Plasma and CSF were collected after an approximately 105-minute infusion.

MAIN OUTCOME MEASURES:

Plasma and CSF levels of interleukin 1alpha, interleukin 1beta, interleukin 6, tumor necrosis factor alpha, F2-isoprostane (CSF only), Abeta, norepinephrine, transthyretin, and apolipoprotein E.

RESULTS:

Insulin increased CSF levels of F2-isoprostane and cytokines (both P<.01), as well as plasma and CSF levels of Abeta42 (both P<.05). The changes in CSF levels of Abeta42 were predicted by increased F2-isoprostane and cytokine levels (both P<.01) and reduced transthyretin levels (P = .02). Increased inflammation was modulated by insulin-induced changes in CSF levels of norepinephrine and apolipoprotein E (both P<.05).

CONCLUSION:

Moderate hyperinsulinemia can elevate inflammatory markers and Abeta42 in the periphery and the brain, thereby potentially increasing the risk of Alzheimer disease.

PMID:
16216936
DOI:
10.1001/archneur.62.10.noc50112
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center